TW200526665A - Pyrrolopyrimidine thion derivatives - Google Patents

Abstract

A compound represented by the following formula (I), which has inhibitory activity against GSK-3. In the formula, A1 and A3 each is a single bond or an aliphatic hydrocarbon; A2 and A4 each is a single bond, CO, COO, CONR, O, OCO, NR, NRCO, NRCONR etc.; G1 is a single bond, alicyclic hydrocarbon, aromatic hydrocarbon, etc.; G2 is hydrogen, an aliphatic hydrocarbon, alicyclic hydrocarbon, aromatic hydrocarbon, etc.; A5 is a single bond or NR; R2 is hydrogen, halogeno, an aliphatic hydrocarbon alicyclic hydrocarbon, aromatic hydrocarbon group etc.; A6 is a single bond, NR, CO, NRCO, NRCONR, CONR, COO, O etc.; and R3 is a hydrogen, halogeno, nitro group, saturated aliphatic hydrocarbon alicyclic hydrocarbon, aromatic hydrocarbon, etc.; provided that R is hydrogen or a lower aliphatic hydrocarbon group.

Description

200526665 (1) IX. Description of the invention [Technical field to which the invention belongs] ‘The present invention relates to a novel pyrrolopyrimidone derivative having a blocking effect on liver sugar synthase kinase-3 (GSK-3). More specifically, diseases that are related to GKS-3 activity are particularly related to glucose tolerance disorders, type 1 diabetes, type 2 diabetes, and diarrhea (omental disease, nephropathy, neurological disorders, large blood vessels). Disorders, etc.), Alzheimer's disease, neurodegenerative diseases (AIDS, chorea, Parkinson's disease, amyotrophic spinal sclerosis, multiple sclerosis, etc.), bipolar mood disorder (manic depression), trauma Cerebral Spinal Cord Injury, Apical Hypertrophy, Atherosclerosis, Hypertension, Polycystic Ovarian Syndrome, Syndrome X, Hair Removal, Inflammatory Diseases (Deformable Joint Syndrome, Rheumatism, Allergic Dermatitis, psoriasis, ulcerative colitis, clonal disease, sepsis, systemic inflammatory response syndrome, etc.), cancer, and immunodeficiency, etc. are very useful for the treatment and / or prevention of novel pyrrolopyrimidone derivatives. [Prior art] GSK-3 is a serine / threonine kinase, identified as two isoforms of alpha and cold encoded by each gene (Trends Biochem. Sci. 1991, Vol. 16, ρ · 177). Each of the GSK-3 isoforms is constructed from monomers, and resting cells are often activated. GSK-3 was originally identified as a kinase that can block its activity by directly phosphorylating glycogen synthase (Eur · J · Biochem ·, 1980, Volume 107, ρ · 519). It is speculated that, under insulin stimulation, the inactivation of GSK-3 will cause the activation of hepatic glucose synthase (2) (2) 200526665, which may also cause insulin-transporting action such as sugar. In addition, GSK-3 is also known to be inertized by other growth factors such as IGF-1 or FGF, or via information from the receptor tyrosine kinase (see Biochem. J .. UK , Vol. 294, 1993, p.62 5; Biochem. J. UK, Vol. 3, 003, P21; Biochem. J. UK, Vol. 03, 1 994, p.27). GSK-3 blockers are useful for treating various diseases for which GSK-3 activation is the cause. In addition, the blocking factor of GSK-3 can mimic the activation of the growth factor message transmission pathway, so it is also useful for the treatment of diseases in which the inertia of the message transmission pathway is the cause. Examples of various diseases in which GSK-3 blockers are presumed to be effective are shown here. Type I diabetes is caused by / 3 cells of insulin-producing cells in the pancreas caused by autoimmune destruction, and those lacking insulin. It can be seen that, in order to maintain life, patients with type I diabetes must frequently administer insulin daily. However, today's insulin treatments cannot reproduce the tight blood glucose control as normal Θ cells. Therefore, type I diabetes can easily induce diabetic outbreaks such as omental disease, nephropathy, neurological disorders, or macrovascular disorders. Type II diabetes is a multifactorial disease that usually results in hyperglycemia due to insulin resistance in the liver skeletal muscle and adipose tissue, and insufficient insulin secretion from the pancreas. As a result, diabetic episodes such as omental disease, nephropathy, neurological disorders, or macrovascular disorders can be induced. The skeletal muscle system can absorb the main tissues of glucose by insulin stimulation, and the absorbed glucose is metabolized through either the glycogenolysis system / TCA cycle or the accumulation of glucose. The accumulation of glucose in skeletal muscle has a very important task in terms of maintaining glucose. Π (3) (3) 200526665 patients with diabetes have lower glucose accumulation in skeletal muscle. GSK-3 will phosphorylate liver glucose synthase, block the accumulation of liver glucose in peripheral tissues, reduce insulin reactivity, and promote the tendency of blood glucose to increase. Recently, it has been reported that GSK-3 can increase the performance of skeletal muscle in type II diabetes. There is an inverse correlation between skeletal muscle GSK-3 α activity and insulin action (see Diabetes, USA, 2000, Vol. 49, ρ.263) ° Excessive expression of GSK-3 cold and activated GSK-3 cold variants (S9A, S9E) in HEK-293 cells results in inhibition of hepatic glucose synthase activity (see Proc. Natl. Acad. Sci., USA, Vol. 93, 1996, p. 1 0228). In CHO cells that express insulin receptors and insulin receptor matrix 1 (IRS-1), overexpression of GSK-3 causes insulin-lowering effects (see Proc. Natl. Acad. Sci., USA, 1997, 94 Vol., P · 9 6 6). Recent studies using c 5 7 BL / 6 J mice with a tendency to obese diabetes have shown the association between GSK-3 hyperactivity and insulin resistance / type II diabetes progression (see Diabetes, USA; 1 9 99 (Vol. 48, p. 1 662). Lithium salts have been known as agents that block GSK-3 activity in the past (see Proc. Natl. Acad. Sci. USA, 1 996, Vol. 93, p.84 5 5). It has also been reported that although the use of lithium salts can reduce the blood glucose level of type 1 and type 2 diabetic patients, it can improve the condition (see Biol. Trace Elements Res., 1997, Vol. 60, p.131). However, there are reports that lithium salts have various effects on molecular targets other than GSK-3. From the above, it can be speculated that the GSK-3 blocker should be an effective agent for improving tolerance disorders, type I diabetes, type II diabetes, or its scurvy. 8- (4) (4) 200526665 Also, GSK -3 also shows a correlation with the symptoms of Alzheimer's disease. Alzheimer's disease is characterized by the formation of senile plaques in the brain due to the precipitation of amyloid Θ peptide (A /?), And the subsequent formation of neuronal fiber changes. These changes can lead to the death of a large number of nerve cells and present with symptoms of dementia. It is speculated that GSK-3 is associated with the abnormal phosphorylation of microtubule-binding proteins that are associated with neuronal fiber changes during the progression of this condition (Acta Neuropathol ·, 2002, Vol. 103, p. 91) . There are also reports that GSK-3 blockers can prevent neuronal cell death (see J. Neurochem., 2001, Vol. 77, p. 94). It can be speculated that the adaptation of GSK-3 blocker to Alzheimer's can delay the progress of this disease. At present, although Alzheimer's disease medicine is used for symptomatic therapy (refer to Expert Opin · Pharmacother ·, 1999, Vol.1, ρ · 121), it does not prevent the death of nerve cells and delay the deepening of the disease. Pharmacy. From the above, it can be speculated that the GSK-3 blocker should be an effective agent to improve Alzheimer's dementia. It has been reported that GSK-3 blockers can inhibit neuronal cell death, especially neuronal cell death caused by glutamate overexcitation (see Prco · Natl. Acad · Sci "USA, 1998, Vol. 95, p.2642; J Neurochem ·, 2001, vol. 77, ρ · 94). This incident shows that GSK-3 blockers have effects on bipolar affective disorder (manic depression), epilepsy, or various degenerative brain diseases and nerves. Possibly useful for the treatment of the disease. In addition to the above-mentioned Alzheimer's disease, neurodegenerative diseases include AIDS, chorea, Parkinson's disease, amyotrophic spinal sclerosis, multiple sclerosis, Becker Disease, advanced -9- (5) (5) 200526665 paralytic nucleus paralysis, etc. In addition, the hyperexcitable line via glutamic acid is presumed to be stroke (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage), Causes of brain disorders such as traumatic brain and spinal cord injuries, bacterial / viral infections, and GSK_3 blockers are also expected to be useful for these diseases. These are diseases that can cause neuronal cell death. There is still no effective disease at this time. Agent that inhibits this neurocyte death. Known from the above GSK-3 blockers are expected to be effective agents for improving various neurodegenerative diseases, bipolar affective disorder (manic depression), epilepsy, stroke, and traumatic brain / spinal cord injury. It has also been reported that the Wint 10B line strongly inhibits the differentiation of preadipocytes into mature adipocytes (see Science, 2000, Vol. 29, p. 95 0), and GSK-3 specific blockers are preadipocytes. The stabilization of the Wint 10B message can stabilize the free / 3-catenin (stone-catenin) existing in the cytoplasm, inhibit C / EBP α and PPAR r derivation, and inhibit adipogenesis (see J. Biol. Chem. 2002, Vol. 277, p. 30998). From the above, it can be seen that GSK-3 blockers are expected to be effective agents for treating plumpness. Moreover, it is known that / 3-catenin is a kind of GSK-3 In vivo matrix. / 5 · Catenin systems can be phosphorylated by GSK-3 and undergo proteasome-dependent decomposition (see EMBO · J ·, 1998, Vol. 17, ρ · 1371). On the other hand, it is presumed to be temporary Θ-catenin stabilization system also bears the role of hair development Users (refer to Cell, 1998, Vol. 95, P.605). From the above, it can be known that GSK-3 / 3 blockers have been tested as effective agents for the treatment of hair loss. In addition, the relevant research on GSK- 3 Fibroblasts from unstunned mice (6) 200526665 also showed that GSK-3 yS could squarely regulate the activity of the transcription factor NFkB (see Nature, 2000, Vol. 406, ρ · 86). The NFkB line is cellularly responsive to most inflammatory stimuli. From the above, it can be known that GSK-3 blocker can reduce NF k B activity through regulation, and can be used as a treatment for deformable joint disease, rheumatism, allergic dermatitis, psoriasis, ulcerative colitis, coulomb disease, Septicemia, systemic inflammatory response syndrome, and inflammatory diseases are effective agents.

The NF-AT of the transcription factor can be dephosphorylated by calcineurin to enhance the immune response (see Science, 1997, Vol. 275, P.1930). The GSK-3 line phosphorylates NF-AT and instead transports it out of the nucleus, and tends to suppress the expression of genes in the initial immune response. From the above, it can be seen that the GSK-3 blocker can be used as an effective drug for inactivating and immunizing cancer, such as cancer immunotherapy.

Previously known substances with GSK-3 blocking activity have been reported as Hymenialdisine derivatives (see Chemistry & Biology 2000, Volume 7, P. 51 and International Publication No. 0 1/4 1 7 6 8), Maleimide imine derivatives (see Chemistry & Biology, 2000, Vol. 7, ρ · 793), paullone derivatives (see Eur. J. Biochem., 2000, Vol. 267, P. 5 98 3 and International Publication No. 0 1/6 03 74), Purine Derivatives (see International Publication No. 9 8/1 6 5 2 8), Pyrimidine and Pyridine Derivatives (see International Publication No. 99/65 897), Derivatives of Hydroxyflavon (Refer to International Publication No. 00/1 7 1 84), pyrimidone derivatives (refer to International Publication No. 00/1 8 7 5 8, International Publication No. 0 1/706 8 3, International Publication No. 0 1 / 70 72 9 and International Publication No. 0 1/70728, International Publication No. 0 1/7072 7, International Publication No. 0 1/70726 and International Publication No. -11-(7) 200526665 01/70725), Approval Slightly -2,5-dione derivatives (refer to International Publication No. 00/2 1 92 7 and International Publication No. 0W74771), diamino-1, 2, 4, triazole -Carboxylic acid derivatives (refer to International Publication No. 0 1/09 1 06) pyrazine derivatives (refer to International Publication No. 0 1/4 4 2 0 6), bicyclic blockers (refer to International Publication No. 01 / 44246), inderubine derivatives (refer to International Publication No. 0/1/3 7 8 19), carboxamide derivatives (refer to International Publication No. 0 1/4 2 2 24), peptide blocking agents (refer to International Publication No. 01/4 9 7 09)

, 2,4-diaminothiazole derivatives (refer to International Publication No. 01/5/6567), thiadiazolysine dione derivatives (refer to International Publication No. 01/1 5 6 85), aromatic Group amide derivatives (refer to International Publication No. 01/8 1 3 4 5), etc.

In addition, a wide range of compounds containing pyrrolimidine derivatives are shown in the scope of patent application of International Publication No. 0 2/0 8 5 9 0 9. However, in fact, the synthesized cyclic pyrrolidine derivative is a 7-position substituent of the pyrrolidine ring, and other substitutable positions are limited to a few number of substituents. Although a method for evaluating the activity of GSK-3 blocking activity is described, there is no specific disclosure as to which compound has the activity. [Summary of the Invention] The object of the present invention is to provide a novel compound which is selective for GSK-3 and has a strong blocking effect, which is clinically applicable, and a GS K-3 blocker using it as an active ingredient Pharmaceutical composition. Another object of the present invention is to provide a therapeutic or preventive agent for GSK-3 related diseases. -12- (8) 200526665 It is another object of the present invention to provide a method for treating GSK-3 related diseases. The inventors of the present invention made the following researches as a result of the above-mentioned objects, and completed the following inventions. That is, the compound of the present invention represented by the following formula (I) or a medically acceptable salt thereof.

A2—G1—A3—A4-G2 (I) In formula (I), A1 represents a single bond or a bivalent acyclic formula in which a nitrogen atom bonded to A1 and A2 are bonded at the same or different carbon atoms. Aliphatic hydrocarbon group,

A2 is a single bond or a group that binds A1 and G1 in the following forms: A] -C (= 〇) -G1, A] -C (= 〇) -O-G1, A ^ C (= 〇)- NR101-G], A] -C (= s) -NRI02-G], A 丨 -C (= NR) 03) -G1 'A] -0 -G 1 > A] -0 -C (= 〇 ) -G 1, A] -NRl 04-G] -13- (9) 200526665 A ^ NR ^ -C (= 0) -G], A〗 -NR106-S (= 0) 2-G1, A ' NR ^ -C (= 0) -0-G1, ai_NR] 08-C (= 0) _NRi〇9-G], A1 -NR1 10-C (= S) -G1, A ^ NR1 1] -C ( = S) -NR1 12-G] ^ A ^ S-G1

A] -S (= 0) -G1, A! -S (= 0) 2-G1, A1 -S (= 0) 2-NR1 " -G1, A ^ CR1 14 = CH-G1 ^ A ^ CR1 15 = CF-G1 'aLci ^ crulg1, or A ^ CF ^ CR1 H-G1.

G1 is a single bond, or C3 ~ C1G fatty hydrocarbon group which can be substituted, C6 ~ C14 aromatic hydrocarbon group which can be substituted, and 1 to 4 in the ring which can be substituted. It is selected from oxygen, nitrogen and sulfur. A divalent group obtained by removing two hydrogen atoms in any of the heterocyclic compounds grouped by atoms, A3 shows a single bond or C, which can be substituted by making Gi and V bond on the same or different carbon atoms, ~ ClG Valence acyclic aliphatic hydrocarbon group, A4 represents a single bond, or a group which allows 2 〃 G to bind in the following form, A3-C (= 0) -G2, A3-C (= 0) -〇-G2, A3- C (= 0) -NR12LG2, _14 · (10) 200526665 A3-C (= S) -NR122-G2, A3_c (= NR) 23) _G2, a3-o-g2, A3-0-C (= 0) -G2, a3-nr124-g12 A3-NRI25-C (= 0) -G2, A3-NR126-S (= 0) 2-g2, A3-NR127-C (= 0) -O-G2, A3-NR ] 28-C (= 0) -NR〗 29-G2, Φ A3-NR] 30-C (= S) -G2 'A3-NR131-C (= S) -NR132-G2, A3-S-G2, A3-S (= 0) -G2, A ^ -S (= 0) 2 ~ G ^ 'A3-S (= 0) 2-NR133-G2, or AJ-S (= 0) 2-0-G2' G2 shows a hydrogen atom, which can be substituted by an acyclic aliphatic hydrocarbon group, and C3 ~ C1G alicyclic hydrocarbon group which can be substituted, which can be substituted by Instead of c6 ~ CM aromatic hydrocarbon group, or a heterocyclic group having 1 to 4 atoms selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom in the ring which can be substituted, A5 shows a single bond or -NR2 () 1, R2 represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a non-cyclic aliphatic hydrocarbon group which may be substituted, 3 to 8 alicyclic hydrocarbon group, which may be substituted C6 ~ Cl4 aromatic hydrocarbon group, or may be substituted -15- (11) 200526665 In the ring, there are 1 to 4 heterocyclic groups selected from the group consisting of oxygen, nitrogen and sulfur atoms. A5 shows a single bond or The carbon atom of the pyrrole ring that binds R3 and a6 is a group bonded in the following form: R3-NR3Q1-pyrrole ring, R3-C (= 0) -pyrrole ring, R3-NR302-C (= 〇) -ti ratio Ring, R3-NR3G3-C (= s), pyrrole ring,

R3-NR3G4-C (= 0) -nr3G5-pyrrole ring, R3-C (= 0) = 0) -0-D specific ring, R3-0-C (= 0) -pyrrole ring,

R3-〇-role ring, r3-s-pyrrole ring, r3-s (= o) -pyrrole ring, R3-S (= 0) 2-pyrrole ring, R3-NR3G8 = CR3 () 9-pyrrole ring, R3-C Ξ CD specific ring, or R3-S (= 0) 2-C Tri-C-ring ring R3 does not have a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, or a nitro group, and may be substituted. c 1 ~ c 1 0 non-cyclic saturated aliphatic hydrocarbon group, which can be substituted C3 ~ Cs alicyclic hydrocarbon group, which can be substituted c6 ~ cM # aromatic hydrocarbon group 'which can have 1 to 4 in the substituted ring It is selected from the group consisting of oxygen atom, nitrogen atom and sulfur-16- (12) (12) 200526665 atom. The heterocyclic group of A6-R3 may be A or R3-CR3G8 = rCR3G9. R3-C tri-C-pyrrole ring is a group that binds R3 to the carbon atom of the pyrrole ring, and R3 may be a trimethylsilyl group, a methyl group, or a substituted C2 ~ C7 group, a carboxyl group, or C2 ~ C7 alkoxycarbonyl and carbamoyl groups, which may be substituted [2 ~ 〇7 alkylamine formamidine, or a combination of cyano groups, where R 1G1- R 1 17, R1 2 1- R133, R2G1, and R3G1- R3G3 independently shows a hydrogen atom or an acyclic aliphatic hydrocarbon group, but A1 and A3 each show an acyclic aliphatic hydrocarbon Based at least any one of A2 or G1 is not a single bond. The present invention is a pharmaceutical composition made of the compound represented by the above formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The present invention is a GSK-3 blocker comprising the compound represented by the above formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. In addition, the present invention is a therapeutic or preventive agent for GSK-3 related diseases comprising the compound represented by the above formula (I) or a medically acceptable salt thereof as an active ingredient. In addition, the present invention is a method for treating a GSK-3-related disease including a process of administering a therapeutically effective amount of the compound represented by the above formula (I) or a medically acceptable salt thereof to a patient. Also, the A ^ G2 part in the above formula (I) can be combined by A], A2, G] 'A3, A4, and G2, and when there are substituents, the combination including these substituents Due to different combinations, sometimes -17- (13) 200526665 shows different substituents. However, this does not make the scope of the present invention unclear. -X 'can be derived from the compound represented by the formula (I) of the present invention through the pyrrolopyrimidine derivative represented by & T $ (11), and the corresponding pyrimidinethione derivative can be derived.

In the formula (II), the meanings of A], A2, A3, A4, A5, A6, G1′g2, and R3 are the same as those of the formula (I). χ indicates a chlorine atom, a bromine atom, an iodine atom, a sulfanyl group of C2 to c1 (), an alkoxymethylthio group of C2 to c8, an alkyl group of 1J, or a sulfonyloxy group of c to c8 $. Pyrrolidine, which is represented by formula (VII), is sharply sprayed :). Yan Dao / "7 Dou, Rui Ming 尔 Er hj 1 Yu η biological manufacturing intermediates of the following

· N_ (Ic) A2—G1—A3—A4—q2 In formula (1C), the definitions of A !, A2, A3, eight 4, eight, and R3 are the same as those of formula (I) -18, A6, Gi and Q are (14) (14) 200526665 c2 ~ c1G fluorenyl, C2 ~ C1G alkoxymethyl 'which can be substituted or benzyl which can be substituted. [Embodiment] The "acyclic aliphatic hydrocarbon group" in this specification includes a linear or branched acyclic aliphatic hydrocarbon group, as long as it is an acyclic aliphatic hydrocarbon group, it may be saturated, which is chemically possible. Ranges can have one or more double or triple bonds. "Alkyl" in this specification means, for example, dimethyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, isopropyl, isobutyl, second butyl, third butyl , Non-pentyl, neopentyl, third pentyl and isohexyl linear and branched saturated acyclic aliphatic hydrocarbon groups. The "pyridyl" in this description also includes its N-oxide. The "cycloalkyl group" in this specification means a saturated aliphatic hydrocarbon group such as cyclopropyl, cyclobutyl, and cyclohexyl. The "heterocyclic ring" in this specification means that as long as the ring has 1 to 4 monocyclic to tricyclic rings selected from the group consisting of oxygen, nitrogen, and sulfur atoms, and is chemically stable, it does not It is particularly limited, except that the ring contains 1 to 3, preferably 1 to 2 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, and a monocyclic or bicyclic carbon number of 9 or less. should. In the above formula (I), A 1 represents a single bond, or a divalent acyclic aliphatic hydrocarbon group of Cl to C 6 in which a nitrogen atom to which A 1 is bonded and A 2 is bonded to the same or different carbon atoms. Examples of the C ^ C: 6 acyclic aliphatic hydrocarbon group of A1 include methane, ethane-19- (15) 200526665, propane, butane, 2-methylpropane, pentane, and 2-methylbutane. , 2,2-dimethylpropane, hexane, 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane, 2,3-dimethylbutane, and 2, 2,3-trimethylpropane is a divalent group obtained by removing two hydrogen atoms, respectively. Examples of this A1 are -CH2-,-(CH2) 2-,-(CH2) 3 ·,-(CH2) 4-,-(CH2) 5, ·,-(ch2) 6-, -CH (CH3) -,-CH (ch3) ch2-, -ch (ch3) ch (ch3)-, -c (ch3) 2ch2-, -ch (ch3) (ch2) 2-, -CH2CH (CH3) CH2-,-CH (CHs) CH (CHs) C2-, -CH (CH3) CH2CH (CH3)-, -CH2C (CH3) 2CH2-, -CH (CH3) C (CH3) 2CH2-, -CH (CH2CH3) (CH2) 2 -, -CH2CH (CH2CH3) CH2-, CH (CH2CH3) CH (CH3) CH2-, -CH (CH3) CH (CH2CH3) CH2-, -CH (CH2CH3) CH2CH (CH3)-, -CH (ch3) (ch2) 3-, -ch2 (c.h3) (ch2) 2-, -ch (ch3) CH (CH3) (CH2) 2-, -CH (CH3) CH2CH (CH3) CH2-, -CH2CH (CH3 ) CH (CH3) CH2-, -CH2C (CH3) 2 (ch2) 2-, -ch (CH3) C (CH3) 2CH2-, -CH (CH2CH3) (ch2) 3-, -ch2ch (ch2ch3) (ch2 ) 2 ·, _CH (ch3) (ch2) 4-, _ch2ch (ch3) (ch2) 3-, _ (ch2) 2ch (ch3) (c H 2) 2-. These preferred examples are -c H 2-,-(c H 2) 2-,-(CH 2) 3-, _ (CH2) 4_, -CH (CH3) CH2-, -CH (CH3) CH ( CH3)-, -CH (CH3) (CH2) 2-, -CH2CH (CH3) CH2-, -CH (CH3) CH (CH3) CH2-. This a] is more preferably -CH2-,-(CH2) 2-, and (CH2) 3. The best case is-(ch2) 2. • 20- (16) 200526665 In the above formula (I), A2 is a single bond, or A 1 and G 1 are represented by A] -C (= 0) -G 1, A1-c (= 0) -O-G1 , Al-C (= 〇) -NR 101-G] 'A 丨 -c (= S) -NR], 02-G i, A ^ C (= NRI〇3)-G1, A1-A ^ O- G1 0- G1-A] 1 -OC (= 〇) -G1 ^ A1 -NR] 04- G1, A 1-NR 10 5-C (= 0) -G 1, A1- NR10 6- s (= 0 ) 2- G1, A1 -NR1 0 7 _ C (= 0)-0 -G1-A1 -NR108 -c (= 〇) -NR109- G1 > A1 -NR1 1 0 _ c (= s)-G 1 , A1 -NR1 1 Jc (= s) -NR112-G!, A1 』-C (: = 0) -G 1, A 1-: S (= 0) -G 丨 1, A, S (= 〇) 2-G1, A] -S (= 〇) 2 · NR]] 3-G],, A1- CR114 = CH-G1, A ^ CR ^^ CF-G1, A 1-CH = CR 1 15-G 1, A1-

C ^ CRm-G1 form binding base. (R1G1 to R117 each independently represent a hydrogen atom or an acyclic aliphatic hydrocarbon group of C to C4). When A1 and G1 are combined in the form of A, C (= 0 -NR1G), examples of the acyclic aliphatic hydrocarbon group of Crh of R 101 may be methyl, ethyl, propyl, isopropyl , Butyl, isobutyl, second butyl, third butyl, cyclopropylmethyl, 2-propenyl, 2-butenyl, cobutenyl, 2-propynyl

, 2-butynyl, and 3-butynyl. The acyclic aliphatic hydrocarbon group of Cl to C4 can be further selected from one or more fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxyl group, methoxy group, ethoxy group, oxy group, cyanexide m ^ ^ The Θ group, the carboxyl group, the carbamoyl group, the amine group, the sulfonic acid group, and the phenyl group are substituted by ^ w & 101 ~ K groups. Preferable examples of the R 1 G 1 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferred for the + # '. A] When G1 is combined with A1-C (= S) -NR1.2. 2 G, C of R102] ~ C4 Examples of acyclic aliphatic hydrocarbon groups can be described in the example of R1 () 1 above. Show. Preferred examples of the R 1G 2 are a hydrogen atom, a methyl group, a hydrogen atom, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferable. • 21-(17) (17) 200526665 When A1 and G1 are combined in the form of A, (: (= ΝΙ11 () 3) -G1, the C! ~ C4 acyclic aliphatic hydrocarbon group of R1G3 can be exemplified as The above examples of R1 () 1 are shown. The preferred examples of R 1 ^ are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, particularly a hydrogen atom. A1 and G1 are A ^ NR ^^ G1 When the forms are combined, examples of the acyclic aliphatic hydrocarbon group of R1 () 4 may be as shown in the above examples of R1 ^ 1. The preferred examples of the R1 () 4 are a hydrogen atom, a methyl group, and an ethyl group. And propyl, especially a hydrogen atom is preferred. When A1 and G1 are bonded in the form of A ^ NR ^ -C (= 0) -G1, an example of C! ~ C4 acyclic aliphatic hydrocarbon group of 111 () 5 It may be as shown in the above example of R1 () 1. Preferred examples of the R] G5 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, particularly a hydrogen atom. A1 and G1 are A ^ NRi When ^ -S (0) 2-G1 is combined, examples of C ^ C: 4 acyclic aliphatic hydrocarbon group may be as shown in the above example of R1G1. The preferred examples of R106 are a hydrogen atom, a Group, ethyl group and propyl group, especially hydrogen atom is preferred. Eight 1 and 01 are in the form of eight] ^ 111. 7-(: (= 0) -0-0], when R1 ^ C ^ C4 Acyclic Examples of the aliphatic hydrocarbon group may be as shown in the above example of R ^. The preferred examples of the R1G7 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and particularly a hydrogen atom is preferred. A1 and G1 are represented by A ^ NRMS-CCrO) NR】 G9-G】 When combined, the examples of Ci ~ C4 acyclic aliphatic hydrocarbon groups of R1 and R1G9 may be as shown in the above example of R1Q1. The best of r1G8 and r1G9 Examples are hydrogen atom, methyl, ethyl and propyl, especially hydrogen atom is preferred. -22- (18) (18) 200526665 A and G are A] -NRliG-C (= S) -G] When the forms are combined, an example of the C! ~ C4 acyclic aliphatic hydrocarbon group of R] 10 may be as shown in the above example of R 1 ^. Preferred examples of the R 11 () are a hydrogen atom, a methyl group, and an ethyl group. And propyl, especially a hydrogen atom is preferred. A] When combined with G1 in the form of A ^ NR ^ -C (= S) -NR112-G], the C ^ C4 acyclic aliphatic hydrocarbon group of RM1 and R112. Examples may be as shown in the above example of R 1 ^ 1. The preferred examples of R 1 1 1 and R 1 12 are a hydrogen atom, a methyl'ethyl group, and a propyl group, and particularly a hydrogen atom is preferred. A1 When combined with G1 in the form of A ^ SCO) ^ NR ^ -G1, an example of the Crh acyclic aliphatic hydrocarbon group of Rii3 may be as described above for R1gi Examples are shown. The preferred examples of R113 are hydrogen atom, methyl group, ethyl group and propyl group, especially hydrogen atom is preferred. When A1 and G1 are combined in the form of aLcrH ^ CRM-G1, Rim and R115 Examples of C ^ C: 4 acyclic aliphatic hydrocarbon group may be as shown in the example of rim described above. Preferred examples of the R114 and R115 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferable. When A1 and G1 are combined in the form of ALCFtCR ^ -G1, an example of the C! ~ C4 acyclic aliphatic hydrocarbon group of Rii7 may be as shown in the above example of RUi. Preferable examples of the R117 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferable. The better of A2 is that A1 and G1 are set to 8-(: (= 〇) -〇1, 8-C (= 〇) -NRWi-G1, A ^ O-G1, aLNRW'G1, a ^ NRHS-C (= 0) -G], A] -NR108-C (= 0) -ΝΙΙ109 ^ 1, a ^ NRHO-C (= S) -G1, and A ^ NI ^ H-CM ^ S ) NR " 2-G], -23- (19) 200526665 《WA】 -C (= O) -G1, A1-C (= O) -NR10】 -g1, A1-NR] 04 -G], A] -NR105-C (= 0) -G], A ^ -Nΐΐΐ08- ^: (= 〇) -NRi〇9-Gi, and aLnrUG-C (= S) -G1 are preferable. Among them, the best of a2 is A! And G! With A] -C (= 〇) · Κ101-〇ι, aLnr105-C (= 0). Gi, A ^ NRW-C (= 0)-NrW -G1 form combination base. The combination of the better example A 'and the better example of A2 is more suitable for combination with the structure of A1 · (CH2) 2- or-(CH2) 3- in formula (I). 'A3 in the above formula (I) represents a single bond, or represents a Cl ~ C1G divalent acyclic aliphatic hydrocarbon group which may be substituted by bonding G1 and A1 to the same or different carbon atoms. The example of the acyclic aliphatic hydrocarbon group of the CrCK of the 8-3 is the same as the above example of Aι, and may also be -CH = CH-, -C (CH3) = CH-, -c (ch3) = c ( ch3)-, -c (ch2ch3) = ch-, -C (ch2ch3) = C (CH3), -C (CH2CH3) = c (CH2CH3)-'-C (CH2CH2CH3) = CH-, -C (CH2CH2CH3 ) = C (ch3)-, -CH = CHCH2-, -C (CH3) = CHCH2 ·, -CH = C (CH3) CH2-, -CH = CHCH (CH3)-, -C (CH3) = C ( CH3) CH2-, -C (CH3)-= CHCH (CH3)-, -c (CH3) = C (CH3) CH (CH9)-, -C (CH3) = CHC (CH3) 2-, -C ( CH2CH3) = CHCH2-, -CH = C (CH2CH3) -CH2-, -CH = CHCH (CH2CH3)-, -c (ch2ch3) = c (ch3) ch2-, -c (ch2ch3) = CHCH (CH3)- , -C (CH3) = C (CH2C3) CH2- '-CH = C (CH2CH3) CH (CH3)-, -CH = CHCH (CH2CH9)-, -C (CH3) = CHCH (CH2CH3)-, -CH = C (CH3) CH (-24- (20) 200526665 CH2CH3)-> -CH = CH (CH2) 2-, -C (CH3) = CH (CH2) 2-, -CH = C (CH3) ( CH 2) 2-, · CH = CHC (CH 3) CH 2-'-CH = CHCH2CH (CH3)-, -C (CH3) = C (CH3) (CH2) 2-, -c (ch3) two chch ( ch3) ch2-, -c (ch3) = chch2ch (ch3)-, -ch2ch = chch2-, -ch (ch3) CH = CHCH2-,-CH2C (CH3) = CHCH2-, = CH (CH3) C (ch3 ) = chch2-, -ch (ch3) ch = chch (ch3)-, -CH (CH3) CH = C (CH3) CH2-, -CH2C (CH3) = C (ch3) CH2-, -CH (ch2ch3) ch = chch2-, -ch2c (ch2ch3) = chch2-. The divalent acyclic aliphatic hydrocarbon group of A3 is a substituent C when substituted] ~ C6 hydrocarbon group, c3 ~ c6 aliphatic hydrocarbon group, halogen atom, alkoxy group, phenoxy group, amine group, or K 6 alkane Amine. The preferred examples of A3 are single bonds, -CH2- '-(CH2) 2-,-(CH2) 3-,-(ch2) [, -ch (ch3) ch2-, -CH (ch3) ch (ch3) -, _CH (CH3) (CH2) 2-, -CH = CH-, preferably CH CHCH2, ° more preferably a single bond, -ch2-,-(ch2) 2-, and (ch2) 3-. Therefore, the same applies when A is substituted, except for single bonds.

In the above formula () _G2, A3-C c (= 0) -G2,) shows a single bond or shows that a3 and G2 use A3-C (= 0

〇) -〇-G2, A3-C (= 〇) -NR] 21-G2, A3-C (= s) -NRU2, g2 A3-C (= NR) 23) -G2, A3-0-G2 Α3 · 0- A, NR124-G2, A3-NR125, C (= 0) -G2, A3-

NR 1 2 6 s (= 〇) 2, G2, a3-NR] 27-C (= 0) -0-G2, A3-NR! 2 8 c (= o) -nr] 29 • G, A3-NR130 -C (= S) -G2, A -NR C (A3'S ·. 2, A3-S (= 0) -G2, A3-S (= 0) 2- -25- (21) (21) 200526665 G 'A _S (= 〇) ”NR-G, A-S (= 〇), 〇-G2 (r121-r133 are independently hydrogen atom or cr ^ ™. L 1 ~ C 4 Acyclic aliphatic hydrocarbon group) ^ When G2 is combined with Ale (= 0) -NRm-G2, the example of C ^ C: 4 acyclic aliphatic hydrocarbon group of R121 can be r1G1 @ 户 of A2 above It is different. The preferred examples of the R121 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, especially a hydrogen atom. A3 and G2 are combined in the form of A3-C (= S) -NR122-G2 At the time, the example of the acyclic aliphatic hydrocarbon group of rI22 may be the same as the above A2 ^ Rl () 1_ & $. The preferred examples of the R122 are a hydrogen atom, a methyl group, an ethyl group and a propyl group, especially a hydrogen atom. When A3 and G2 are combined in the form of A3-C (= NR123) -G2, an example of R] 23 (^ ~ 〇: 4 acyclic aliphatic hydrocarbon group may be r1G1m m _ of human 2 The preferred examples of this R123 are a hydrogen atom, a methyl group, And propyl, especially hydrogen atom is preferred. When A3 and G2 are combined in the form of A3-NR124-G2, r! 24 of c] ~ c4 Examples of acyclic aliphatic hydrocarbon groups may be R1G1 of A2 above. The preferred examples are the hydrogen atom, methyl, ethyl and propyl, especially hydrogen atom. A3 and G2 are in the form of A3-NR125-C (= 0) -V When combined, the examples of C 1 to C 4 acyclic aliphatic hydrocarbon groups of R 1 h may be the same as those shown in the above R 2 G 1 example of A 2. The preferred examples of R 125 are a hydrogen atom, a methyl group, and a ethyl group. In particular, a hydrogen atom is preferred as the propyl group and the propyl group. When A3 and G2 are combined in the form of A3-R126-S (= 0) -G2, R126 -26- (22) (22) 200526665 of C! ~ C4 is not Examples of the cyclic aliphatic hydrocarbon group may be the same as those shown in the above-mentioned examples of R 1G1 of A2. Preferred examples of the R126 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and particularly a hydrogen atom is preferred. A3 and G2 are When combined in the form of A3-NR127-C (= 0) -O-G2, examples of C! To C4 acyclic aliphatic hydrocarbon groups of R127 may be the same as those shown in the rim example of A2 above. Preferred examples of the R127 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferred. When A3 and G2 are combined in the form of A3-NR128-C (= 0) -NR129-G2, the examples of the acyclic aliphatic hydrocarbon groups of R128 and R129 may be the same as those shown in the above example of R1 () of a2. Preferred examples of the R128 and R129 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferable. When A3 and G2 are combined in the form of A3-NR13G-C (= S) -G2, the examples of C] ~ C4 acyclic aliphatic hydrocarbon group of r130 may be the same as those shown in the above-mentioned RU1 example of A2. Preferred examples of the R13 () are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferred. When A3 and G2 are combined in the form of A3-NR131-C (= S) _NR132-G2, the examples of Cl ~ C4 acyclic aliphatic hydrocarbon groups of R131 and R132 may be the same as those shown in the above R101 of a2. Preferred examples of the R131 and R132 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferable. When A3 and G2 are combined in the form of A3-S (= 0) -NR133-G2, an example of the K4 acyclic aliphatic hydrocarbon group of r133 may be the same as m 2 of the above two. Preferred examples of the R133 are a hydrogen atom, a methyl group, an ethyl group, and a propyl group, and a hydrogen atom is particularly preferred. The better of A4 is a single bond, A3 and G2 use A, C (, • 27- (23) (23) 200526665 A3-C (= 0) _0-G2, A3-C (= 0) -NR ] 2] -G2, A3-0-G2, A3-nr124-g2, a3-nr] 25-c (= 〇) _G2, A, s (= 0) 2. G2, and a3_s (= 〇) 2- 0-g2 form bonded group. G1 in the above formula (I) shows a single bond, or c3 ~ c10 aliphatic hydrocarbon group which can be substituted C6 ~ C! 4 aromatic hydrocarbon group, which can be substituted The ring has a divalent group obtained by removing two hydrogen atoms from any one of the heterocyclic compounds of the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. G1 in the above formula (I) represents that it may be substituted. When c3 ~ C1G is a divalent aliphatic hydrocarbon group, the C3 ~ C1G aliphatic hydrocarbon group may be, for example, cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cycloheptane, Cycloheptene, cyclooctane, bicyclo [2.2.1] heptane, bicyclo [2.2.1] heptene, bicyclo [3.1.1] heptane, bicyclo [2.2.1] octane, adamantane, etc. The ( The preferred alicyclic hydrocarbons of 51 (: 3 to 0:10) are cyclopropane, cyclopentane, cyclohexane, and cyclohexanone monocyclic alicyclic smoke such as cyclohexane. The substituent when C3 ~ C1G alicyclic hydrocarbon group of G1 is substituted may be fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxyl group, methoxy group, propoxy group, isopropoxy group, butoxy group, iso Butoxy, second butoxy, third butoxy, pentyloxy'isopentyloxy, neopentyloxy, second pentyloxy, hexyloxy, isohexyloxy, 2-methylpentyloxy Methyl, 1-ethylbutoxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cyclopropylmethoxy, cyclopropylethoxy, cyclopentylmethoxy And straight-chain or branched courtyards such as cyclohexylmethoxy, or cyclo ~ anyl and Cl ~ C * 7 ~, and diethylene oxide, etc. Ci ~ C4 Shenyuan dioxy Aryloxy, phenoxy, α-phenethoxy, cold-phenethoxy-28- (C6 ~ C1 (), phenoxy, 1 · Caioxy, and 2.naphthyloxy, etc. 24) (24) 200526665, and arylalkoxy, ethoxyl, propylpyroxy, butylpyroxy, isobutylpyroxy, pentyloxy, isopentyl, etc. Methoxy, trimethylethoxy, and hexamethoxy C, formed by a linear or branched chain, such as ethylsulfonyloxy, propylsulfonyloxy, butylsulfonyloxy, and second butylsulfonyloxy, and fluorenyloxy ^ C6 fluorenylsulfonyloxy, ethylfluorenyl, propylfluorenyl, butylfluorenyl, isobutylfluorenyl, pentylfluorenyl, trimethylethylfluorenyl and hexamethylfluorenyl, etc. C2 ~ 07, fluorenyl, carboxyl, methoxy Linear or branched alkyl and oxycarbonyl groups such as carbonyl, ethoxycarbonyl, propoxycarbonyl, isopropyloxy, butoxycarbonyl, isobutoxycarbonyl, second butoxycarbonyl, and third butoxycarbonyl , Aminomethyl, N-methylaminomethyl, N-ethylaminomethyl, N-propylaminomethyl, N-isopropylaminomethyl, N-butylaminomethyl Methyl, N-isobutylamine formamyl, second butylaminoformamyl, N-third butylaminoformamyl, N-pentylamine formamyl, N-cyclopropylamine formamyl , N-cyclobutylamine formamyl, N-cyclopentylamine formamyl, N-cyclohexylamine formamyl, N-cycloheptylamine formamyl, N-cyclopropylamine formamyl, N, N-Dimethylamine formamyl, N-ethyl-N-methylamine formyl, N, N-diethylamine formamyl, and N N-dipropylamine methylamyl, and other straight or branched chain or cyclic alkyl and carbamoyl groups formed by C2 ~ C7 alkylaminomethyl groups, amino groups, methylamino groups, ethylamino groups, Alanine 'isopropylamine, isobutylamine, second butylamine, third butylamine, pentylamine, hexylamine, cyclodiamine, cyclobutylamine, cyclopentylamine, cyclohexylamine Methyl, cyclopropylmethylamino, dimethylamino, N-ethylmethylamino, diethylamino, N-methylpropylamino, N • methylisopropylamino, N-methylbutylamino, N-methyl tertiary butylamino, isopropylamino, dipropylamino, diisopropylamino, and ethylbutylamino groups such as straight -29- (25) (25) 200526665 chain or branched chain alkyl Or cycloalkyl and amine group (:! ~ 0: 6 alkylamino, acetamido, propylamido, butylamido \ isobutylamido, pentamido, and hexamidine, etc. C2 ~ C7 amido, methoxycarbonyl C2 ~ C8 alkoxycarbonylamino, methylsulfonamido, ethylsulfonamido, butylsulfonamido, and tertiary Alkylsulfonamido, cyano, nitro, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, second butyl Thio, tertiary butylthio, pentylthio, and hexylthio, etc. < ^ ~ (: alkylthio, methylsulfinamido, ethylsulfinamido, propylsulfinamido, Isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, second butylsulfinyl, third butylsulfinyl, pentylsulfinyl, and cyclopentyl Sulfinyl sulfenyl and other linear or branched alkyl or cycloalkyl groups and sulfinyl sulfinyl]] C6 alkylsulfinyl sulfinyl, methylsulfinyl, ethylsulfinyl, and sulfinyl Base, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, second butylsulfonyl, third butylsulfonyl, pentylsulfonyl Sulfonyl, hexamethanesulfonyl, cyclopentylsulfonyl and cycloalkyl and sulfonyl groups, sulfonyl, sulfonyl, sulfamoyl, methylaminosulfonyl, ethylaminosulfonyl, Propylaminosulfonyl, isopropylaminosulfonyl, second butylaminosulfonyl, pentaminosulfonyl, dimethylaminosulfonyl, N-ethylmethylaminosulfonyl, diethyl Linear or branched, such as aminosulfonyl, dipropylaminosulfonyl, cyclopropylaminosulfonyl ', cyclopentylaminosulfonyl, cyclohexylaminosulfonyl and cyclopropylmethylaminosulfonyl ^ ~ (: 6 amine sulfonyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. C 3 ~ 〇6 aliphatic hydrocarbon groups formed by chain alkyl or cycloalkyl and sulfamoyl groups, And methyl, ethyl, vinyl, ethynyl, propyl, h propenyl, 2-propenyl, isopropenyl, isopropenyl, b propynyl, 2-propyn-30- (26) 200526665, Isobutyl, second butyl, third butyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propene Radical, 1-methyl-2-propenyl, 2-methyl-2-propenyl, butynyl, 2-butynyl, pentyl, isopentyl , Neopentyl, third pentyl, popentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, hexyl, 5-hexyl, 4-methyl-3-pentene Group, isohexyl group, 2-methylpentyl group, and ethyl ethyl butyl group, etc. Non-cyclic aliphatic hydrocarbon groups of C! ~ C6 which are linear or branched and may contain one unsaturated bond.

The G1 substituted C3 ~ C1G aliphatic hydrocarbon group is substituted by (^ ~ (^ alkoxy, c2 ~ c7 acid group, c2 ~ C7 alkylaminomethyl group, Ci ~ C6 amino group, C2 ~ C7醯 Amine group, C3 ~ C6 aliphatic hydrocarbon group and Cl ~ C6 # cyclic aliphatic hydrocarbon group can be further modified by (fluorine, chlorine atom, bromine atom, iodine atom, hydroxyl group, methoxy 'group), isopropyloxy group Radical, τoxy, isobutoxy

CrC, such as second butoxy, third butoxy, pentyloxy, and cyclopropoxy, alkoxy, methoxymethyloxy, 2-methoxyethoxy, formamyl, Ethyl trifluoride, ethynyl, propanyl, butyryl, isobutyryl, amyl and isoamyl, etc. C: 2 ~ C: 7 Oxyfluorenyl, ethoxyminyl'-propoxycarbonyl, isopropoxy, oxybutyric, isobutoxy, and dibutoxyfluorenyl, etc. C: 2 ~ q alkoxycarbonylaminomethanyl, N_ Methylamine formamyl, N 'N-dimethylaminoformamyl, N_ethylaminoformamyl, N • ethyl-N-methylaminoformamyl, N' N • diethylamine Formamyl, N-propylamine methyl, N-isopropylamine methyl, N-methylamine methyl, N-cyclopropylamine methyl, and N-cyclopropylmethylamine Formamidine and other G amidylaminomethylammonyl, amino'methylamino, ethylamino, propylamino, isopropylamino, dimethylamino, N-ethylmethylamino, diethylamino, n_ Methylpropylamino, ν-methyl-31-(27) 200526665 Alkylamino groups such as isopropylamino, cyclopropylamino, and cyclopropylmethylamino, 1-pyrrolidinyl, hexahydropyracyl C 4 ~, which contains 1 to 2 groups selected from oxygen, nitrogen, and sulfur atoms in the ring such as methyl, 4-methylhexahydropyridyl, N-hexahydropyridyl, and morpholinyl. C 6 cyclic amine, acetamido trifluoride, formamidine, acetamido, propylamino, butylamino, isobutylamino and pentamidine, etc. Cl ~ C7 acid Ci ~ C6 alkylsulfonamido, nitro, and cyano, such as limbyl, methyl-5amino, ethylsulfoamido, propylsulfoamido, and butylsulfoamido When one or more substituents selected by the group) are substituted. When the above formula (I) is used to represent a divalent aromatic hydrocarbon group of c6 to c14, the aromatic hydrocarbon of C6 to C14 may be, for example, benzene, indene, Compounds having at least one aromatic ring in the molecule, such as indene, naphthalene, 1,2-dihydronaphthalene, 1,2 '3,4-tetrahydronaphthalene, fluorene, pinenenaphthalene, pinnaphthalene, manganese, phenanthrene, and anthracene . Preferred examples of the aromatic hydrocarbons of C6 to C] 4 of G1 include benzene, naphthalene, and indene. A more preferable example of the C6 to CI4 aromatic hydrocarbons of G1 is benzene. The substituted C6 ~ C14 aromatic hydrocarbon group of φ G1 may be a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a Ci ~ C7 alkoxy group, C6 ~ CiG aryloxy group, C7 ~ C9 aroyloxy, C2 ~ C7 cooloxy, steel-based, C] ~ C6 aristolyloxy, C2 ~ C * 7 醯, which can be substituted, residues, C2 ~ C7 alkoxycarbonyl Carbamoyl group, C 2 ~ C 7 alkylaminomethyl group which can be substituted, amine group, C 1 ~ c 6 alkylamino group which can be substituted, c 2 ~ c 7 amine group which can be substituted , C 2 ~ C 8 alkoxycarbonylamino, C! ~ C 6 alkylsulfonamido, cyano, nitro, C, ~ c6 alkylthio, CrQ alkylsulfinyl, fluorenyl, amine- 32- (28) (28) 200526665 Sulfonyl group, Ci ~ C 6 amine sulfonyl group, sulfonic group, c 3 ~ c 6 alicyclic hydrocarbon group, and non-cyclic group which can be substituted Aliphatic hydrocarbon group. The specific examples of the substituents of the C6 to CM aromatic hydrocarbon group which may be substituted for G1 are different from the specific examples of the substituents of the C3 to C1G alicyclic hydrocarbon group which may be substituted for G1 described above. Specific examples of the substituted C6 to CM aromatic hydrocarbon substituents of G1 are alkoxy groups, C2 to C7 fluorenyl groups, C2 to C7 alkylaminomethyl groups, dagger to daggeramino groups, c2 to C7 fluorenylamino groups , C3 ~ C6 alicyclic hydrocarbon group, and acyclic hydrocarbon group, can be more (fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy , Butoxy, isobutoxy, second butoxy, third butoxy, pentyloxy, and cyclopropoxy, such as Ci ~ CJ-membered oxy, methoxymethyloxy, 2-methyl Ethoxyethoxy, methylamino, ethylfluorenyl trifluoride, ethylfluorenyl, propionyl, butylfluorenyl, isobutylfluorenyl, pentamyl, and isopentylmethyl, etc. C2 ~ c7fluorenyl, keto, carboxyl, Methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxy, and di-butoxyfluorenyl, etc. C2 ~ C7 oxonyl, aminomethyl, N · methyl Carbamate, N, N-dimethylamine carbamate, N-ethylamine carbamate, N-ethyl · N-methylcarbamate, N, diethylcarbamate, ... propylamine formamyl, N-isopropylamine formamyl, N-butylamine C2 ~ C7 alkyl amine methyl groups, such as fluorenyl groups, ... cyclopropylaminomethyl methanoyl groups, and N-cyclopropylmethyl carbamomethyl groups, amine groups, methylamino groups, ethylamino groups, propylamino groups, isopropyl groups Propylamino, dimethylamino, N-ethylmethylamino, diethylamino, methylpropylamino, 1methylisopropylamino, cyclopropylamino and cyclopropylmethylamino, etc. (^ ~ € 6 alkane Amino groups, 1-pyrrolidinyl, hexahydropyridyl, 4-methylhexahydropyridyl, N-hexahydropyridine-33- (29) (29) 200526665 Ortho and morpholinyl C4 ~ C6 cyclic amino group, ethyl trifluoride amine group, formamidine group, acetamido group, propylamido group having 1 to 2 atoms selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom C i ~ C 7 amidinyl, methylsulfonamido, ethylsulfonamido, propylsulfonamido, and butylsulfonyl醯 Amino groups such as C! ~ C6 alkyl amine amine groups, nitro groups, and cyano groups selected by one or more substituents) are substituted 〇 The G1 can be substituted C6 ~ C] 4 aromatic hydrocarbon group Preferred examples of the substituent are a fluorine atom, a chlorine atom, a bromine atom, a methoxy group, and an ethyl group. Base, propoxy, isopropoxy, butoxy, isobutoxy, second butoxy, third butoxy, pentyloxy, isopentyloxy, neopentyloxy, second pentyloxy Alkoxy, cyano, nitro, carboxyl, hydroxy, amine, methylamino, ethylamino, propylamino, isopropylamine Base, butylamino, isobutylamino, second butylamino, third butylamino, pentylamino, hexylamino, dimethylamino, N-ethylmethylamino, diethylamino, N -Methylpropylamino, N-methylisopropylamino, N-methylbutylamino, 1methyl-tertiarybutylamino, N-ethylisopropylamino, dipropylamino, diisopropylamino 'and Cl ~ C6 mono- or di-alkylamino, carbamoyl, sulfamoyl, cyclopropyl, cyclobutyl, cyclopentyl C3 ~ C6 alicyclic hydrocarbon groups such as cyclohexyl, ethidium, propionyl, butylfluorenyl, isobutylfluorenyl, pentamyl and hexamethylene, etc. C2 to C7 fluorenyl, methylthio, ethylthio, propyl Thio, isopropylthio, butylthio, isobutylthio, second butylthio , Ξthiylthio, pentylthio, and hexylthio, etc. C] ~ sulphanylthio, methylsulfanyl, ethylsulfonyl, sulfanyl, isopropylsulfonyl, butanyl 34- (30 ) (30) 200526665 sulfofluorenyl, isobutylsulfonyl, second sulfonylsulfonyl, third butylsulfonyl'pentylsulfonyl, and hexanesulfonyl such as hexanesulfonyl, ethylacetoxy, C 2 ~ C7 alkoxycarbonyl, acetamidine, etc., such as propionyloxy, butyryloxy, isobutyryloxy, pentamyloxy, isopentamyloxy, trimethylacetamyloxy and hexamethyleneoxy. C2 ~ C7 amine groups, such as amino groups, propylamino groups, butylamino groups, isobutylamino groups, pentamidine groups and hexamidine groups, trifluoromethyl groups, trifluoromethoxy groups, and methyl groups , Ethyl, vinyl, ethynyl, propyl, 1-propenyl, 2-propynyl, butyl, isobutyl, second butyl, third butyl, 1-butenyl, 2-butene Alkenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 1-butenyl, 2-butenyl , Pentyl, isopentyl, neopentyl, third pentyl, 1-pentyl, 2-pentanyl, 3-pentyl, 4-pentyl, hexyl, 5-pentanyl, 4 -Methyl-3 -pentyl, isohexyl, 2-methylpentyl, and 1-ethylbutyl, etc. may contain a linear or branched unsaturated bond (V ~ c6 acyclic Aliphatic nicotine. Among them, preferred examples of the substituted C6 ~ Cm aromatic hydrocarbon group are fluorine atom, chlorine atom, bromine atom, Ci ~ C6 alkyloxy group, cyano group, nitro group, residue, warp group, amine group, C] ~ C6—or dialkylamino, carbamate, c3 ~ c6 alicyclic hydrocarbon group, C2 ~ C7 fluorenyl, CrC6 alkylsulfonyl, c2 ~ c7 oxonyl group, trifluoromethyl, trifluoro Methoxy, and methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second butyl, third butyl, pentyl, isopentyl, neopentyl, third pentyl C, C ~~ C6, and other preferred substituents are, for example, fluorine atom, chlorine atom, Cl ~ C6 alkoxy group, cyano group, nitrate, etc. Group, residue, mesogenic group, amino group, C ^ -C: 6- or monoamine amino group, c: 3 ~ C: 6 alicyclic hydrocarbon group, ~ c -35- (31) 200526665 fluorenyl group, three Fluoromethyl, trifluoromethoxy, and C] ~ C6 alkyl.

When G1 in the above formula (I) is a heterocyclic group having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring which may be substituted, 1 to 4 atoms selected from oxygen are present in the ring. The heterocyclic compound consisting of atoms, nitrogen atoms, and sulfur atoms may be, for example, furan, thiophene, pyrrole, pyrroline, pyrrolidine, humidazole, humazidine, isonazole, isoxazoline, thiazole, and thiazidine. , Furo, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazidine, triazole, thiadiazole, Uf diazole, tetrazole, piperan, tetrahydropiperan, thiapiperan, tetra Hydrothienine, tetrahydrofuran, 1,3-dioxolane, 1,4-diBoxan, pyridine, pyridine, pyrimidine, dawell, benzofuran, dibenzo Furan, 1,4-di

Ringer cycloheptane, benzothiophene, indole, 1,2-methylenedioxybenzene, benzimidone, benzothionine, benzylidene, late, isolate, songline, ten Hydrogen D-quinoline, iso-D-quinoline, hydrazone, hydrazone, 1,8-pyridine, 1,2,3,4-tetrahydroisoquinoline, quinazoline, D | quinoline, purine, hydrazone Pyridine, acridine, morpholine, thiomorpholine, hexahydropyridine, homohexahydropyridine, hexahydropyrine, homohexahydropyrine, indolinoline, isoindolinoline, phenanthrene, morphine Monocyclic, bicyclic or tricyclic heterocyclic compounds such as cocoa, phenothiazine D, [] pyrrolopyrimidine, pyrazolopyrimidine, and pyrimidine. Preferred examples of the heterocyclic compound having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the G1 ring are furan, pyrrole, thiophene, oxazole, azole, thiazole, isoxazole, and isothiazole. , Pyrazole, imidazole, pyridine, pyrimidine, pyridine, daphne, benzothiophene, benzofuran, 1,2-methylenedioxybenzene, benzimidazole, indole, quinoline, isoxoline, Quinazoline, Sakai, Pyridoxine and 1,1-pyridine have 1 ~ 3 rings selected from the group consisting of oxygen atom, nitrogen atom -36- (32) (32) 200526665 and sulfur atom in the ring Monocyclic or bicyclic C2 ~ C9 aromatic heterocyclic compounds, or crocodile, hexahydroxanthine, morpholine, thiomorpholine, homohexahydropyridine, homohexahydropyramine 1, 1 , 2,3 '6-tetrahydropyridine, and hexahydropyridine, and other rings having 1 to 2 monocyclic C2 to C9 heterocyclic compounds selected from the group consisting of oxygen, nitrogen, and sulfur atoms . The heterocyclic group having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the ring of G1 is bonded to A2 on a carbon atom or a nitrogen atom. A preferable example of a heterocyclic group having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring bonded to A2 on a carbon atom is furan, pyrrole, thiophene, pyrazole, humazole , Thiazole, isoxazole, isothiazole, pyrazole, imidazole, pyridine, pyrimidine, pyrene, daco, benzothiophene, benzofuran, 1,2-methylenedioxybenzene, benzimidazole, indole, Quinoline, isoquinoline, quinazoline, hydrazone, oxoline, and 1,8-pyridine and other rings having 1 to 2 monocyclic rings selected from the group consisting of oxygen, nitrogen, and sulfur atoms A bivalent radical derived from a cyclic or bicyclic C3 ~ C9 aromatic heterocyclic compound. In addition, a preferable example of the heterocyclic group having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring bonded to A2 on a nitrogen atom is pyrrolidine, hexahydropyridine, or morphine 1,2,3,6-tetrahydropyridine, hexahydropyridine, hexahydropyridine, and hexahydropyridine A monocyclic C2 ~ (: 9 divalent group led by a heterocyclic compound consisting of atoms and a group of sulfur atoms. This ring has 1 to 2 atoms selected from oxygen, nitrogen and sulfur atoms. The best examples of monocyclic C2 ~ C9 heterocyclic compounds of group atoms are hexahydropyridine, homohexahydropyridine, morpholine, homohexahydropyridine or hexahydropyridine. -37- (33) (33) 200526665 The substituted ring of G1 which has 1 to 4 heterocyclic groups selected from the group consisting of oxygen, nitrogen and sulfur atoms is a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, and may be substituted by Substituted alkoxy, C6 ~ C10 aryloxy, C7 ~ C9 aralkyloxy, C2 ~ C7 fluorenyloxy, keto, alkanesulfonyloxy, C2 ~ C7 fluorenyl, carboxyl, c2 ~ C7 alkoxycarbonyl, carbamoyl, C2 ~ C7 alkylaminomethyl, which can be substituted, amine, ~ C6 alkylamino, which can be substituted, c2 ~ C7, amine, C2 ~ C8 oxofluorenylamino, C! ~ C 6 sulfosulfanyl, cyano, nitro, ci ~ C 6 sulfonyl, C! ~ C0 alkylsulfinyl sulfonyl, alkylsulfonyl, amine Sulfonyl group, Cl ~ C6 alkylaminosulfonyl group, sulfonic acid group, c3 ~ c6 alicyclic hydrocarbon group which may be substituted, and Ci ~ C6 acyclic aliphatic hydrocarbon group which may be substituted. The G1 is substituted The ring has 1 to 4 heterocyclic substituents selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, and specific examples thereof are the same as those of the substituted C3 to C of G 1 above. The specific examples of the substituent of the hydrocarbon group are the same as those shown in the substituted ring of G1! ~ 4 Cl selected from the substituents of the heterocyclic group consisting of oxygen atom, nitrogen atom and sulfur atom ~ c7 alkoxy, c2 to C7 fluorenyl, C2 to C7 alkylaminomethyl, Cl to 〇6 alkylamino, c2 to c7 amine, C3 to C6 alicyclic hydrocarbon group, and Cl to C6 acyclic Formula aliphatic hydrocarbon group, can be more (fluorine atom, Atom, bromine atom, monument atom, meridian, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, first butoxy, second butoxy, pentyl Oxygen, and cyclopropoxy etc. (: 1 ~ (: 6koxy, methoxymethyloxy, 2-methoxyethoxy, formamyl, shamyl ethyl alcohol, acetamidine C2 ~ c7fluorenyl, keto, carboxyl, methoxycarbonyl, ethoxylate, etc. C2 ~ ^ alkoxycarbonyl groups such as propoxyfluorenyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl and second butoxyquinyl, carbamoyl, methylcarbamate, N 'dimethyl Aminomethyl, N-ethylaminomethyl, N-ethyl-N-methylaminomethyl, n, ... diethylaminomethyl, propylaminomethanyl, N-iso Propylaminomethylammonyl, ... butylaminomethylammonyl, 1cyclopropylaminomethylamyl 'and N-cyclopropylmethylaminomethylammonyl, etc. c2 ~ C7 alkylaminomethylamyl, amine, Methylamino, ethylamino, propylamino'isopropylamino, dimethylamino, N-ethylmethylamino, diethylamino, N-methyl Amine groups such as propylamino, n-methylisopropylamine, cyclopropylamino and cyclopropylmethylamino, i-pyrrole D amidyl, hexahydro Dtt phenyl, 4_methylhexahydropyridinyl, N_hexa Hydropyridyl and morpholinyl, and other rings having C4 ~ C6 cyclic amine groups, acetamidotrifluoride, and formamidine selected from the group consisting of oxygen, nitrogen and sulfur atoms in the ring C ^ C7 amine, methylsulfonylamine, ethylsulfonylamine, propylsulfonylamine, butylsulfonylamine, butylsulfonylamine, butylsulfonylamine, butylsulfonylamine, butylsulfonylamine, butylsulfonylamine, sulfonylamine One or more substituents selected from the group consisting of C! ~ C 6 alkylsulfonamido, nitro, and cyano, such as sulfosulfonamido and butylsulfonamido. In the substituted ring of G], a substituent having 1 to 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a substituted ring. Preferred examples are a fluorine atom, a chlorine atom, a bromine atom, and a methoxy group. Group, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, second butoxy, third butoxy, pentoxy, isopentoxy, neopentyloxy, ^ ~ (: 6 alkoxy, cyano, nitro, carboxyl, hydroxyl, amine, methylamino , Ethylamino, propylamino, isopropylamine, butylamine-39- (35) (35) 200526665, isobutylamine, second butylamine, third butylamine, pentylamine, hexylamine , Dimethylamino, N-ethylmethylamino, diethylamine, ... methylpropylamino, N-methylisopropylamino, N-methylbutylamino, N-methyl tertiary butylamine (N-ethylisopropylamino, dipropylamino, diisopropylamino, and ethylbutylamino) and other straight or branched chain radicals and amine groups Methyl, carbamoyl, sulfamoyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclo C3 ~ C6 alicyclic hydrocarbon groups such as hexyl, ethylfluorenyl, propionyl, butylfluorenyl, isobutylfluorenyl, pentamyl, and hexyl, etc. C: 2 ~ c7 donkey, methylthio, ethylthio, propylthio, isopropyl C i ~ C 6 alkylthio, methylsulfonyl, ethylsulfonyl, propylthio, butylthio, isobutylthio, second butylthio, second butylthio, pentylthio, and hexylthio Ci, sulfenyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, second butylsulfonyl, third butylsulfonyl, pentylsulfonyl, and hexanesulfonyl ~ C6 Extender, Acetyloxy, Propyryloxy, Butyryloxy, Isobutyryloxy, Pentamyloxy, Isoamyloxy, Trimethylethoxyl and Caproate C2 ~ C7, such as oxamine, ethylamine, propylamine, butylamine, isobutylamine, pentamidine and hexamidine, etc. C2 ~ C7 amine, trifluoro Methyl, trifluoromethoxy and methyl, ethyl, ethylene, ethynyl, propyl, 1-propenyl, 2-propynyl, butyl, isobutyl, second butyl, Tributyl, 1-butenyl, 2-butenyl, 3-butenyl, methyl-1-propenyl, 2-methyl -1-propenyl, 1-methyl-2-propenyl, butenyl, 2-butenyl, pentyl, isopentyl, neopentyl, tertiary pentyl, pentyl, 2- Pentenyl, 3-pentenyl, 4-pentenyl, hexyl, 5-hexenyl, 4-methyl-3-pentenyl, isohexyl, 2-methylpentyl, and 1-ethyl Butyl, etc. may contain a linear or branched unsaturated bond C] ~ C6 acyclic aliphatic-40- (36) (36) 200526665 aliphatic hydrocarbon group. Wherein the substituted ring has 1 to 4 selected from Oxygen, nitrogen, and sulfur atom heterocyclic group substituents, preferred examples are fluorine ^ atom 'chlorine atom, bromine atom, C ^ C6 alkoxy group, cyano, nitro, residual Group, hydroxyl, amino group 'C ^ Ce—or dialkylamino group, carbamate group, c3 ~ c6 alicyclic nicotinyl group, C2 ~ C7 fluorenyl group, C] ~ C6 sulfone group, c2 ~ C7 Oxygen residues, methyl trifluoride, methoxy trifluoride, and methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second butyl, third butyl, pentyl Ci-C6, such as methyl, isopentyl, neopentyl, third pentyl, hexyl, isohexyl, 2-methylpentyl, and 1-ethylbutyl A particularly preferred substituent is, for example, a fluorine atom, a chlorine atom, a Cl ~ C6 alkyloxy group, a cyano group, a nitro group, a residue, a warp group, an amine group, Ci ~ C6—or a diamino group, C3 ~ C6 alicyclic hydrocarbon group, c2 to C7 fluorenyl group, methyl trifluoride, methoxy trifluoride, and academic group. In the present invention, G1 in the above formula (1) is formed by a single bond, c3 to C6 monocyclic alicyclic hydrocarbon group, phenylene group, and having 1 or 2 atoms selected from oxygen, nitrogen, and sulfur atoms in the ring. A monocyclic or bicyclic C3 to C9 aromatic heterocyclic group having a group of atoms is preferably a monocyclic C2 to C9 heterocyclic group having 1 or 2 oxygen atoms, nitrogen atoms, and sulfur atoms in the ring. In the above formula (I), G2 is a hydrogen atom, Cl ~ Cl0 acyclic aliphatic hydrocarbon group which may be substituted, C3 ~ C1G alicyclic hydrocarbon group which may be substituted, aromatic hydrocarbon group which may be substituted, or The substituted ring has 1 to 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. In the above formula (I), G2 represents an optionally substituted (^ ~ (: 1 () acyclic aliphatic hydrocarbon group, C of G2) ~ Cu). Examples of acyclic aliphatic hydrocarbon groups are methyl, -41. -(37) (37) 200526665 ethyl, propyl, isopropyl, butyl, isobutyl, second butyl, third butyl, pentyl, isopentyl, neopentyl, third pentyl , 2.methylpentyl, 4-methylpentyl, 1-ethylbutyl, hexyl, heptyl, 2-methylhexyl, 5-methylhexyl '1,1-dimethylpentyl, 6 -Alkyl such as methylheptyl, octyl, nonyl, decyl, vinyl, vinylvinyl, ethylvinyl, 1-propenyl, 2-propenyl, methyl-1-propenyl, butenyl , 2-butenyl, 2-methyl-1-butenyl, 1,3-butadienyl, 1-pentenyl, 2-pentenyl, 4-methyl-1-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1,5-hexadienyl, 2-heptenyl, 2-octenyl , Alkenyl such as 2-nonenyl, 2-decenyl, ethynyl, bupropynyl, 2-propynyl, 1-butynyl, 3-methyl-1-butynyl, 3, 3 -Dimethyl-1-butynyl, 1 -Pentynyl, 2-pentynyl, 3-pentynyl, hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 1-methyl-3 -pentynyl , 1-methyl-3 -hexynyl, 2-heptynyl, 2-octynyl, 2-nonynyl, 2-decynyl, and other alkynyl groups. The 0 2 of the acyclic aliphatic hydrocarbon group Preferred are methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, vinyl, 1-propenyl, 1-butenyl, ethynyl, and 1-propynyl. A linear or branched chain of an unsaturated bond. ^ ~ (: 6 alkyl, especially the most preferred are methyl, ethyl, propyl, isopropyl, butyl, and hexyl, etc. linear or branched (^ ~ 0: 6 alkyl group. The substituted acyclic aliphatic hydrocarbon group of G2 is fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxyl group, methoxy group, propoxy group, isopropyloxy group. Group, butoxy, isobutoxy, second butoxy, third butoxy-42 · (38) (38) 200526665 group, pentyloxy, isopentyloxy, neopentyloxy, secondpentyl Oxy, hexyloxy, isohexyloxy, 2-methylpentyloxy, 1-ethylbutoxy, cyclopropoxy, cyclobutoxy Linear or branched alkyl groups such as cyclopentyloxy, cyclohexyloxy, cyclopropylmethoxy, cyclopropylethoxy, cyclopentylmethoxy, and cyclohexylmethoxy, or C6 ~ Cio aromatics such as alkoxy groups formed by cycloalkyl and oxy groups, ethylene dioxy groups, etc.] ~ C4 alkylene dioxy groups, phenoxy groups, 1-naphthyloxy groups, and 2-naphthyloxy groups. C7 ~ C9 aralkoxy, ethoxyl, propyloxy, butyryloxy, phenylethoxy, α-phenethoxy, cold-phenethoxy, and phenylpropoxy Methyl, isobutyryloxy, pentyloxy, isopentyloxy, trimethylacetoxy, and hexamethyloxy, etc. C, ethanesulfonyloxy, propylsulfonyloxy, butylsulfonyloxy, and tertiary butylsulfonyloxy and the like ] ~ C6 alkylsulfonyloxy, ethylsulfonyl, propionyl, butylfluorenyl, isobutylfluorenyl, pentamyl, trimethylethylfluorenyl and hexamethylene, etc. C2 ~ C7 fluorenyl, carboxyl, methyl Oxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, Linear or branched alkyl groups such as dibutoxycarbonyl and tertiary butoxycarbonyl, and oxycarbonyl, carbamoyl, N-methylaminomethyl, N-ethylaminomethyl, N- Propylamine formamyl, N-isopropylaminoformamyl, N-butylaminoformamyl, N-isobutylaminoformamyl, N-second butylaminoformamyl, N · Tributylamine formamyl, N-pentylamine formamyl, N-cyclopropylamine formamyl, N-cyclobutylamine formamyl, N-cyclopentylamine formamyl, N-cyclo Hexylamine formamyl, N-cycloheptylamine formamyl, N-cyclopropylamine formamyl, N, N · dimethylamine formamyl, N-ethyl-N-methylamine formamidine Linear, -43- (39) (39) 200526665 or branched alkyl or cycloalkyl with amines, N, N-diethylamine formamyl and N, N-dipropylamine formamyl C2 ~ C7 alkylamine methylamine, amine, methylamine, ethylamine, propylamino, isopropylamine, butylaminoisobutylamine, second butylamine, third butyl Amine, pentylamino, hexylamine, cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine, cyclopropylmethylamino, dimethylamino, N-ethylmethylamine, Diethylamino N-methylpropylamino, N'methylisopropylamino, N-methylbutylamino, N-methyl tertiarybutylamino, N-ethylisopropylamino, dipropylamino, diisopropylamino Ci-q alkylamino, acetamido, propylamino, butylamino, isobutyl, etc. formed by linear or branched alkyl or cycloalkyl and amine groups such as ethylamine C2 ~ C7 amidino, pentamido, and hexamidine, C2 ~ C7 amidino, methoxycarbonylamino, ethoxycarbonylamino, and C2 ~ C8 alkoxycarbonylamino such as tertiary oxoamino, Methanesulfonylamino, ethylsulfonamido, butylsulfonamido, and alkylsulfonamido, cyano, nitro, methylthio, ethyl, etc. Thio, propylthio, isopropylthio, butylthio, isobutylthio, second butylthio, third butylthio, pentylthio and hexylthio, etc. (^ ~ 0: 6 alkylthio Methyl, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, second butyl Linear or branched chain such as sulfinyl sulfenyl, third butyl sulfinyl sulfinyl, pentyl sulfinyl sulfinyl and cyclopentyl sulfinyl sulfinyl Alkyl sulfinyl, methanesulfonyl, ethylsulfonyl, sulfonyl, isopropylsulfonyl, butanesulfonyl, isobutyl Sulfonyl, second butanesulfonyl, third butanesulfonyl, pentanesulfonyl, hexylsulfonyl, cyclopentylsulfonyl, and cycloalkyl formed with sulfonyl (^ ~ 0: 6 alkane Sulfonyl, Sulfonyl, Aminosulfonyl, Methylaminosulfonyl, Ethylaminosulfonyl, Alanaminosulfonyl, Isopropylaminosulfonyl, Dibutylamine-44- (40) (40) 200526665 sulfofluorenyl, pentylaminosulfonyl, dimethylaminosulfonyl, ethyl-N-methylaminosulfonyl, diethylaminosulfonyl, dipropylaminosulfonyl , Linear or branched alkyl or cycloalkyl groups such as cyclopropylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl and cyclopropylmethylaminosulfonyl Foundation made (:! ~ 〇 C3 ~ C6 aliphatic hydrocarbon groups such as sulfamoyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and methyl, ethyl, vinyl, ethynyl, propyl, 1-propenyl , 2-propenyl, isopropyl, isopropenyl, propynyl, 2-propynyl, isobutyl, second butyl, third butyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-butynyl , 2-butynyl, pentyl, isopentyl, neopentyl, third pentyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, hexyl, 5 -Hexenyl, 4-methyl-3-pentenyl, isohexyl, 2-methylpentyl, 1-ethylbutyl, and the like. Acyclic or branched Ci ~ C6 non-cyclic aliphatic hydrocarbon groups, benzene, naphthalene'indane, 1,2,3,4-tetrahydronaphthalene, and monocyclic such as manganese C6 ~ 14 aromatic hydrocarbon group of monovalent group guided by cyclic, bicyclic, or tricyclic aromatic hydrocarbon group, as well as furan, thiophene, pyrrole, pyrroline, pyrrolidine, humidazole, harmonica, and isoDf嗤, abnormal sound α sitting, 嚷 D sitting, tiwadine, furo, miguchi sitting, mizu sitting, mizu sitting, D (t D sitting, DU U sitting, D (t). Zidine, trisylidine, thiadiazole, Uf diazole, tetrazole, piperan, tetrahydropiperan, thiopiperan, tetrahydrothiopyran, tetrahydropyran, 1,3-dioxane Wu Yi, 1 '4-Dioxin, Pingding Ding, Biao Ding Ding, Nan Ding Ding, Da Ding Ding, Beni D Furan, Dibenzo D Furan, 1, 4-Dimethylcycloheptane, Benzene Benzothiophene, indole, 1,2-methylenedioxybenzene, benzimidazole, benzothiazole, benzoHfazole, pyrene, isopyrene, D | line, decahydroquinoline, -45- (41) (41) 200526665 iso-D-quinoline, perine, perylene-line, 1,8-pyridine, 1,2,3,4-tetrahydroiso-D-quinoline, quinazoline, Quinoxaline, purine, pyridine, acridine, morpholine, thiomorpholine, hexahydropyridine, homohexahydropyridine, hexahydropyridine, homohexahydropyridine, indoline, isoindole Monovalent, bicyclic or tricyclic heterocyclic compounds led by monocyclic, bicyclic, or tricyclic heterocyclic compounds such as morpholine, phenanthrene, phenanthrene, phenanthrene, phenanthrene, and pyridine (1 to 4 in the ring are selected from oxygen atoms, Atom group formed by nitrogen atom and sulfur atom.) As the substituted G2 (:! ~ (: 1G acyclic aliphatic hydrocarbon group, the preferred examples are fluorine atom, hydroxyl group, and substituted alkoxy group) Group, keto group, C2 ~ C7 alkyl group which can be substituted, carboxyl group, C2 ~ C7 alkoxycarbonyl group, carbamate group, C2 ~ C7 alkylamine group which can be substituted, amine group, which can be substituted ( ^ ~ 06 Alkylamino group, c2 ~ C7 amidino group which may be substituted, alkanesulfonylamino group, cyano group, alkanesulfonyl group, aminesulfonyl group, C6 ~ CM aromatic hydrocarbon group which may be substituted, and Substitutable heterocyclic group (with 1 to 4 atoms selected from the group consisting of oxygen, nitrogen and sulfur atoms in the ring). This G2 may be substituted by a substituted Cl ~ Cl () acyclic aliphatic hydrocarbon group Kyuga Examples are fluorine atom, hydroxyl group, C i ~ C 7 alkoxy group which may be substituted, carboxyl group, amine group, alkylamino group which may be substituted, cyano group, benzyl group, and heterocyclic group which may be substituted (ring It has 4 ~ 4 atoms selected from the group consisting of oxygen atom, nitrogen atom, and sulfur atom. It is a heterocyclic group (substituting in the ring with Cl ~ Cl () acyclic aliphatic hydrocarbon group as a substituent. 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom) are attached to a carbon atom or a nitrogen atom, and are combined with C] ~ C] 〇 acyclic aliphatic hydrocarbon group- 46-(42) (42) 200526665 A heterocyclic group bonded to a non-cyclic aliphatic hydrocarbon group of 02 on the carbon atom (the ring has 1 to 4 atomic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom The preferred examples are from furan, pyrrole, thiophene, pyrazole, humazole, thiazole, isoxazole, isothiazole, pyrazole, imidazole, pyridine, pyrimidine, pyrene, dagen, benzothiophene, benzofuran 1,1,2-methylenedioxybenzene, benzimidazole, indole, quinoline, isoquinoline, quinazoline, etc. have 1 to 2 selected from the group consisting of oxygen atoms and nitrogen atoms in the ring Atom and a sulfur atom as a group, one group is a divalent monocyclic or bicyclic aromatic heterocyclic compound C3~C9 the boot. On the other hand, a heterocyclic group (having 1 to 4 atoms selected from an oxygen atom, a nitrogen atom, and a sulfur atom in the ring) bonded to the C acyclic aliphatic hydrocarbon group of G2 on the nitrogen atom is preferred. Examples are pyrrolidine, hexahydropyridine, morpholine, thiomorpholine, homohexahydropyridine, homohexahydropyridine, 1,2,3,6-tetrahydropyridine, and hexahydropyridine The monovalent C2 to C9 heterocyclic compound guided by a monocyclic C2 to C9 heterocyclic compound having 1 to 2 atoms selected from the group consisting of oxygen, nitrogen, and sulfur atoms in the ring. Among the substituents of the substituted acyclic aliphatic hydrocarbon group of G2, ~ C7 alkoxy, fluorenyl, C2 ~ C7 alkylaminomethyl, Cl ~ C6, amino, C2 ~ C7, amine, C3 ~ C6 alicyclic hydrocarbon group, and acyclic aliphatic hydrocarbon group, C6 ~ C] 4 aromatic hydrocarbon group and heterocyclic group (the ring has 1 to 4 atoms selected from the group consisting of oxygen atom, nitrogen atom, and sulfur atom Group) is more suitable for (fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, second butadiene Oxy, tertiary butoxy, pentyloxy, and cyclopropoxy, etc. (^ ~ alkyloxy, methoxymethyloxy, 2-methoxyethoxy, formamyl, trifluoro Acetyl-47- (43) (43) 200526665, Ethyl, Propyryl, Butyryl, Isobutylamyl, Pentamyl and Isoamyl, etc. C2 ~ C 7 amidyl, keto, carboxyl: C2 ~ C7 alkoxycarbonyl, carbamoyl, N-methylamine formamidine, etc., such as oxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and third butoxycarbonyl N, N-dimethylamine formamidine , N-ethylamine formamyl, N-ethyl-N-methylaminoformamyl, N, N-diethylaminoformamyl, N-propylaminoformamyl, N-isopropyl C2 ~ C7 alkylaminomethyl, amino, etc., such as aminomethylamino, N-butylaminomethylamino, N-cyclopropylaminomethylamino, and N-cyclopropylmethylaminomethylamino Methylamino, ethylamino, propylamino, isopropylamino, dimethylamino, N-ethylmethylamino, diethylamino, N-methylpropylamino, N • methylisopropylamine, cyclopropylamine Ci ~ C6 alkylamino groups, such as alkyl and cyclopropylmethylamino groups, 1-Cyclopyridine, hexahydro D ratio, 4-methylhexahydropyridyl, N-hexahydropyridyl, and morpholine C4 ~ C6 cyclic amino groups, acetamidotrifluoride, formamidine, acetamidoamine, etc., having 1 to 2 atoms selected from the group consisting of oxygen, nitrogen and sulfur atoms in the ring Propylamino, butylamino, isobutylamido and pentamidine, etc. (^ ~ (: 7amido, methylsulfoamido ', ethylsulfoamido, propylsulfoamido Alkylsulfonylamino groups such as alkyl and butylsulfonylamino, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second Group and one or more substituents selected from the group consisting of an alkyl group such as a tributyl group, a trifluoromethyl group, and a trifluoromethoxy group. G2 in the above formula (1) is c3 ~ When c1 () is an alicyclic hydrocarbon group, the C3 ~ C1G alicyclic hydrocarbon group of G2 may be, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, Cycloheptenyl and cyclooctyl. C3 ~ C of this G2] Preferred examples of G alicyclic hydrocarbon groups are cyclopropyl-48- (44) (44) 200526665, cyclobutyl, cyclopentyl, cyclo Hexyl, 3-cyclopentenyl, cyclopentyl, 1-cyclohexenyl, 3-cyclohexenyl, heart cyclohexenyl, and cycloheptyl. G2's substituted C3 ~ C1G alicyclic hydrocarbon group is a substituent selected from the group consisting of gas atom, chlorine atom, bromine atom, iodine atom, hydroxyl group, and C which can be substituted] ~ C7 alkoxy group, C! ~ C4 butane Dioxy, C6 ~ C1G aryloxy, c ~ r 7 ~ L 9 aralkoxy, C2 ~ C7 methoxy, keto, c ^ c: 6 alkanesulfonyloxy, C2 ~ C? Fluorenyl, residue, C2 ~ C7 oxonyl, carbamoyl, C2 ~ C7 alkylaminomethyl, which can be substituted, amine, Ci ~ C6 ^ amino, which can be substituted, but Substituted C2 ~ C? Amine group, C: 2 ~ (: 8 alkoxycarbonylamino group, alkanesulfonylamino group, cyano group, nitro group, thio group, Cl ~ c6 ^ sulfinyl group, c] ~ C6 sulfonyl, sulfamoyl, C! ~ C6 amine sulfoxanthenyl, sulfonate, C3 ~ C6 alicyclic hydrocarbon group, C ^ C6 acyclic The aliphatic hydrocarbon group and the substituted group consisting of C6 ~ Cm aromatic nicotyl groups which can be substituted. Specific examples of the substituted group of C2 ~ C of G2 are the substituents of alicyclic hydrocarbon group as the substituted of G2 described above. The substituent of the acyclic aliphatic hydrocarbon group may be included in the above. Those in the range. ® The substituted C3 ~ C1G alicyclic hydrocarbon group of G2, Cl ~ c6 oxo, C2 ~ C7, and C2 ~ C: 7 oxamine, methylamine, amine, C2 ~ C7 amine group, C3 ~ C6 alicyclic hydrocarbon group, c! ~ C6 acyclic aliphatic hydrocarbon group 'and C6 ~ M aromatic hydrocarbon group can be further (fluorine atom, chlorine atom, bromine atom, iodine atom, Hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, second butoxy, third butoxy, pentoxy, and cyclopropoxy, etc. C] ~ C6 oxygen, methoxymethyloxy, 2- -49- (45) (45) 200526665 methoxyethoxy, formamyl, ethenyl trifluoride, ethenyl, C2 to C7 fluorenyl, keto, keto, carboxyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropyloxy, and butoxycarbonyl , Isobutoxycarbonyl and tertiary butoxycarbonyl, such as c2 ~ c7 alkoxycarbonyl, carbamoyl, N-methylaminomethyl, N, N-dimethylaminomethyl, N-ethylamine Formamyl, N-ethyl-N-methylamine Formamyl, N, N-diethylamine Formamyl, N-propylaminoformamyl, N-isopropylamineformamyl 'N-butylamineformamyl, N-cyclopropylamineformamyl, and N-cyclopropylmethyl C2 ~ C7 alkylamine methylamine, amine, methylamino, ethylamino, propylamino, isopropylamino, dimethylamino, N-ethylmethylamino, diethylamino , N-methylpropylamino, N-methylisopropylamino, cyclopropylamino, and cyclopropylmethylamino groups, such as Ci ~ C6 amine groups, 1 卩 th thoryl, hexahydropyridyl, 4 -C6 ~ C6 cyclic amine groups having 1 to 2 atoms selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom in the ring such as methylhexahydropyridyl, N-hexahydropyridyl and morpholinyl , Triethylamine, methylamine, methylamine, ethylamine, propylamino, butylamino, isobutylamino, and pentamidine, and other sulfonyl groups Ci ~ c6 alkylsulfonic acid amine, nitro, cyano, methyl, ethyl, propyl, isopropyl , Butyl, isobutyl, second butyl, and third butyl, etc.] ~ 06 alkyl, methyl trifluoride, and methyl trifluoride One or more substituents selected from the group consisting of oxy. When G2 in the above formula (I) is an aromatic hydrocarbon group of c6 to c14 which may be substituted, the aromatic hydrocarbon of C6 to C μ of G2 may be, for example, benzene, indene, hydroindene, naphthalene, 1,2-dihydro Naphthalene, 1,2 '3,4-tetrahydronaphthalene, molybdenum, naphthalene, fluorene-50- (46) (46) 200526665 naphthalene, manganese, phenanthrene, and anthracene have at least one aromatic ring in the molecule base. A preferred example of the C 6 to c 1 aromatic hydrocarbon of G 1 is phenyl. G 2 substituted C 6 to C 14 square aromatic nicotyl substituents may be from fluorine atom, chlorine atom, bromine atom, hydrogen atom, hydroxyl group, C! ~ C 7 alkoxy group, CrCA Alkyldioxy, C6 ~ CiG aryloxy, C7 ~ (: 9aralkoxy, C2 ~ C7 fluorenyloxy, keto, Cl ~ C6 alkylsulfonyloxy 'can be substituted C2 ~ C? Fluorenyl, carboxyl, C2 ~ C7 alkoxycarbonyl, carbamoyl, C2 ~ C7 alkylaminomethyl, which may be substituted, amine, alkaminoamino which may be substituted, C2 ~ C7, which may be substituted Amine group, C2 ~ C8 alkoxycarbonylamino group, Cl ~ c6 alkazine stilbene amine group, cyano group, nitro group, Ci ~ C6 alkanethio group, CrCs alkanesulfinyl group, c 1 ~ C 6 Group, amine fluorenyl group, C ~~ C6 amine sulfonyl group, sulfonic group, C3 ~ C6 alicyclic hydrocarbon group which can be substituted, and Cl ~ C6 acyclic aliphatic hydrocarbon group which can be substituted and can be substituted One or more substituents are selected from the group of substituted C6 to CM aromatic hydrocarbon groups. Specific examples of the substituents of the C 6 to C! 4 aromatic hydrocarbon groups which may be substituted for the G2 are the same as those of the acyclic groups which may be substituted for the G2 described above. The specific examples of the substituents of the aliphatic hydrocarbon group of formula A specific example of the substituent of the substituted C6 to CM aromatic hydrocarbon group of G2 is ^ ~ (^ 院 oxy ~ ^ ~ ^ 随 基 ~ ^ ~ ^ 院 基 胺 甲 醯Group, ^ ~ ^^^ hydrazine group, C2 ~ C? Amine group, C3 ~ C6 alicyclic hydrocarbon group, (^ ~ 匚 6 acyclic aliphatic hydrocarbon group and C6 ~ Cm aromatic hydrocarbon group, can be more (Fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy 'second butoxy' third but C] ~ C6 alkoxy, methoxymethyloxy-51-(47) (47) 200526665, 2-methoxyethoxy, formamidine Methyl, ethyl trifluoride, ethyl fluorenyl, propyl fluorenyl, butyl fluorenyl, isobutyl fluorenyl, pentyl fluorenyl and isopentyl fluorenyl etc. C2 ~ 07 fluorenyl, keto, carboxyl, methoxycarbonyl, ethoxycarbonyl , Propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and third butoxycarbonyl C2 ~ c7 alkoxycarbonyl, carbamoyl, N-methylaminoformyl, n, N- Dimethylamine formamyl, N-ethylaminoformamyl, N-ethyl-N -Methylaminomethylmethyl, N, N-diethylaminomethyl, N-propylaminomethyl, N-isopropylaminomethyl, N-butylaminomethyl, N- C2 ~ C7 alkylamine methylamido, amine, methylamine, ethylamino'propylamine, isopropylamine, Methylamino, N-ethylmethylamino, diethylamino, N-methylpropylamino, N-methylisopropylamino, cyclopropylamino, and cyclopropylmethylamino, etc. C] ~ C6 alkylamino groups '1-pyrrolidinyl, hexahydropyridyl, 4-methylhexahydropyridyl, N-hexahydropyridyl, and morpholinyl have 1 to 2 rings selected from oxygen, nitrogen, and C4 ~ C6 cyclic amine group, sulfur trifluoride acetamidoamine group, formamidine group, acetamido group, propylamino group, butylamino group, isobutylamine group and pentyl group Cl ~ C7 alkylamino groups such as fluorenylamino groups, methyl-5 luteimino groups, ethylsulfonamido groups, propylsulfonamido groups, and butylsulfonamido groups, etc. Cl ~ C6 alkylsulfonamido groups, Nitro, cyano, methyl, ethyl, propyl 'isopropyl, butyl, isobutyl, second butyl and third butyl, etc.

Cl ~ ^ 'substituted with one or more substituents selected from the group consisting of methyl trifluoride methyl group and trifluoromethoxy group. When G2 in the formula (I) is a heterocyclic group having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring that may be substituted, for example, furan, thiophene, pyrrole, and pyrrole Chloro, pyrrolidine, oxazole, oxazoline, -52- (48) (48) 200526665 isocrocodazole, isoxazoline, thiazole, thiazolidine, isothiazole, isothiazolidine, imidazole, imidazoline, imidazolidine , Pyrazole, pyrazoline, pyrazidine, triazole, thiadiazole, oxadiazole, tetrazole, piperan, tetrahydropiperan, thiopiperan, tetrahydrothiopiperan, pyridine, pyrazine, pyrimidine , Dagen, benzylfuran, dibenzofuran, benzothiophene, indole, 1,2-methylenedioxybenzene, benzimidazole, benzothiazole, benzimidazole, pyrene, isofluorene, quinone Quinoline, decahydroquinoline, isotiquinoline, Dquinazoline, Dquinoline, purine, pyridine, acridine, morpholine, thiomorpholine, hexahydropyridine, homohexahydropyridine, Monocyclic, bicyclic or tricyclic heterocyclic compounds such as hexahydropyrine, homohexahydropyrine, indolin, isoindolin, phlox, phlox, phlethio, and pyridine Lead out one The preferred examples of the heterocyclic group having 1 to 4 heterocyclic groups selected from the group consisting of oxygen, nitrogen, and sulfur atoms in the ring of G2 are 2-pyridyl, 3-pyridyl, and 4-pyridyl. Fluorenyl, N-hexamethylpyridyl, 2-hexamethylpyridinyl, 3-hexamethylpyridyl, 4-methylpyridyl, 4-hexahydropyridyl, morpholinyl, 1-homohexylpyridine , 1-pyrrolidinyl, 2-thiazolyl, 3-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-Dfazolyl, 5-humazolyl, 1-imidazolyl , 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-imidazolyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxalyl, 3 -Gallyl, 4-isohumidazolyl, 2-pyrimidyl, 4-pyrimidyl, 4-pyrimidyl, 2-pyrimidyl, 4-triazolyl, 5-tetrazolyl, 1-hexahydropyridine Hydrazyl, 4-tetrahydropiperanyl, 2-1,3,4-humidazolyl, 4-1,2,3-thiadiazolyl, 2-benzofuranyl, 2-benzothiazolyl , 2-indolyl, 3-indolyl, 5-benzimidazolyl, and 2-1,2,3,4-tetrahydroisoDquinolinyl. -53- (49) (49) 200526665 This G2 has 1 to 4 rings selected from oxygen A heterocyclic group consisting of a group of atoms, nitrogen atoms, and sulfur atoms is bonded to A4 on a carbon atom or a nitrogen atom. The ring bonded to A4 on the carbon atom has i ~ 4 selected from oxygen atoms, Preferred examples of the heterocyclic group of the nitrogen atom and the sulfur atom group G2 are from furan, pyriole, thiophene, D [t, t, t, t, t, t, t, t, t, Pyrazole, imidazole, pyridine, pyrimidine, pyrazine, dazine, benzothiophene, benzofuran, 1'2-methylenedioxybenzene, benzimidazole, indole, quinoline, iso-D-quinoline, D | The oxazoline and other rings have 1 to 2 monovalent or bicyclic C 3 to C 9 aromatic heterocyclic compounds selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms. . In addition, a preferable example of the heterocyclic group having G2 selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring bonded to A4 on a nitrogen atom is pyrrolidine, hexahydropyridine, Morpholine, thiomorpholine, homomorpholine, homohexahydropyridine, 1,2,3,6-tetrahydropyridine and hexahydropyrine, etc. have 1 to 2 rings selected from oxygen atoms in the ring, A monovalent group derived from a monocyclic C2 to C9 heterocyclic compound of an atomic group formed by a nitrogen atom and a sulfur atom. The best example of the heterocyclic group of G2 can be from hexahydropyridine, hexahydropyridine, morpholine, hexahydropyridine, or hexahydropyrine. A monovalent group derived from a monocyclic C4 to C6 heterocyclic compound of an atomic group consisting of an atom, a nitrogen atom, and a sulfur atom. The substituted ring of G1 which has 1 to 4 heterocyclic groups selected from the group consisting of oxygen, nitrogen and sulfur atoms is a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, and a radical. Substituted Ci ~ C7 alkoxy, Ci butane dioxy, C6 ~ C 丨 0 aryloxy, C7 ~ C9 aralkyloxy, C2 ~ C7 alkoxy (50) (50) 200526665, keto, 0! ~ (: 6 alkanesulfonyloxy group, c2 ~ c7 fluorenyl group which can be substituted, carboxyl group, C2 ~ C7 oxonyl group, carbamoyl group, C2 ~ C7 carbamoyl group which can be substituted , Amine group, c! ~ C6 alkylamino group which can be substituted, c2 ~ c7 amine group, C2 ~ c8 alkoxycarbonylamino group, sulfanylamino group, cyano group, nitro group, Cl ~ C6 alkylthio, α ~ (: 6 alkylsulfinyl sulfenyl group, alkyl sulfanyl group, amine sulfonyl group, C ^ C6 alkylamino sulfonyl group, sulfonic acid group, C3 ~ C6 alicyclic ring which can be substituted One or more substituents selected from the group consisting of a substituted hydrocarbon group, an acyclic aliphatic hydrocarbon group that may be substituted, and a substituted C6 to Cm aromatic hydrocarbon group. The substituted ring of G2 has 1 to 4 members selected from the group. Miscellaneous groups of oxygen, nitrogen and sulfur atoms A specific example of the substituent of the cyclic group is the substituted C] ~ C! Of the above-mentioned G 2. The specific examples of the substituent of the acyclic aliphatic hydrocarbon group may be included in the above range. The G2 In the substituted ring, there are! ~ 4 heterocyclic groups selected from the group consisting of oxygen atom, nitrogen atom, and sulfur atom in the substituent group <: 1 ~ (: 7 oxo group, C2 ~ C7 醯Group, c2 ~ C7 alkylaminomethyl group, (^ ~ (^ alkylamino group, c2 ~ C7 alkylamino group, C3 ~ & alicyclic hydrocarbon group, Cl ~ C6 acyclic aliphatic hydrocarbon group and CeX! 4 Aromatic hydrocarbon groups can be further modified by (fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, second C ^ C6 alkoxy such as butoxy, third butoxy'pentyloxy, and cyclopropoxy, methoxymethyloxy, 2-methoxyethoxy, formamyl, difluoro C2 to C7 fluorenyl, ethynyl, ethynyl'propionyl, butanyl isobutyryl, penthsyl and isopentyl, keto, residues, methoxycarbonyl, ethoxycarbonyl, propoxy Carbonyl, isopropoxycarbonyl, butoxy-55- (51 ) (51) 200526665 carbonyl, isobutoxycarbonyl and tertiary butoxycarbonyl C2 ~ C7 alkoxycarbonyl, carbamoyl, N-methylaminomethyl, N, N-dimethylaminomethyl , N-ethylamine formamyl, N-ethyl-N-methylaminoformamyl, N, N-diethylaminoformamyl, N-propylaminoformamyl, N-isopropyl C2 ~ C7 alkylaminomethane, amine, N-butylaminomethane, N-cyclopropylaminomethane, N-cyclopropylmethylaminomethane, etc. Methylamino, ethylamino, propylamino, isopropylamine, dimethylamino, N-ethylmethylamino, diethylamino, N-methylpropylamino, N-methylisopropylamine, cyclopropylamine Alkylamines such as alkyl and cyclopropylmethylamino, 1-pyrrolidinyl, hexahydropyridyl, 4-methylhexahydropyridinyl, N-hexahydropyridyl, and morpholinyl have 1 to 2 C4 ~ C6 cyclic amino groups, acetamidotrifluoride, formamidine, acetamido, propionamido, selected from the group consisting of oxygen, nitrogen and sulfur atoms Butylamino, isobutylamidino and pentamidine, methylsulfonamido, ethylsulfonamido, propylsulfonamido Alkylsulfonamido groups such as butylsulfonylamino, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second butyl, and third butyl, etc. One or more substituents selected from the group consisting of alkyl, trifluoromethyl, and trifluoromethoxy. When the substituents G1, G2, and G3 in this specification are a substituted aromatic hydrocarbon group, a substituted alicyclic hydrocarbon group, or a substituted heterocyclic group, the aromatic hydrocarbon group, alicyclic hydrocarbon group, or The heterocyclic group is selected from the group consisting of cyclopropane, cyclopentane, cyclohexane, cycloheptane, orthobornane, adamantane, benzene, naphthalene, indene, indole, 1,3-benzodioxane, benzene Benzimidazole, benzotriazole, pyrazole, imidazole, D-pyrazolinone, thiazole, tetrazole, 1,2,4-humidazole, -56- (52) (52) 200526665 isimidazole, furan, Thiophene, pyridine, pyridine, pyrrole, morpholine, benzofuran, benzothiophene, hexahydropyridine, pyrrolidine, hexahydropyridine, homohexahydropyridine, tetrahydroisoD | line, pyrimidine, and oxazoline Those in groups are better. Next, a description is given of a preferred combination of A1, A2, G1, A3, A4, and G2 in the above formula (I). When both A1 and A2 represent an acyclic aliphatic hydrocarbon group, at least either of A2 or G1 is not a single bond. The preferred combinations of A1, A2, G1, A3, A4, and G2, and the preferred combinations including these substituents when they have substituents are basically A1, A2, G1, A3, A4, and A4, respectively. G2 and these substituents are preferably combined. And in combination, it is better to combine each other with the better. In the formula (I), A1 is preferably a bivalent acyclic aliphatic hydrocarbon group, particularly one represented by-(CH2) 2- or-(CH2) 3-. Among them, it is best to use A2 as the other than a single bond, especially A2 as-C (= 〇)-, -c (= 0) · 0-,-(: (= 0) -NH-, -C (= 0) -NVle '-NH-, -NH-C (= 0)-, -NH-C (= 0) -〇-, -NH-C (20) -NH-, -NH-C ( = 〇) -NMe-, or -NH-C (= S)-. Among them, A2 is especially -C (= 〇) · ΝΗ-, -NH-, -NH-C (= 0)-, · NH-C (= 〇) -〇_, or -NH-C (= 〇) -NH- is preferred. When A1 is a single bond, a2 is preferably a single bond. G 1-G2 The preferred combination of G 1, A 3, A4, and G2 may be a combination of 1 to 10 in the following table. -57- (53) (53) 200526665 Combination G] A3 A4 G2 1 Single bond other than a single bond Single bond hydrogen atom 2 Single bond other than single bond Single bond hydrogen atom 3 Single bond other than single bond Single bond other than hydrogen atom 4 Single bond other than single bond hydrogen atom 5 Single bond Bases other than single bonds Bases other than single bonds Other than hydrogen atoms 6 Bases other than single bonds Single bases other than single bonds Other than hydrogen atoms 7 Bases other than single bonds Other than single bonds Other than single hydrogen atoms Base 8 other than single bond A radical other than a single hydrogen atom A radical other than a single hydrogen atom 9 A radical other than a single bond A radical other than a single bond A radical other than a single bond 10 A single bond single bond A single hydrogen atom A2 in combination 4 and combination 7 is shown as C ] ~ C3 alkylene is preferred. In combination 5, A4 is shown-c (= 0)-, -C (= 0) -NH ·, -Ο-, or -NH-C (= 0) -Is more suitable. Also, '4' is not suitable for combination 8 in combination 8. In addition, the following combinations (a) to (f) are suitable. (A) A] shows-(CH2) 2- or -(CH2) 3— Α2τκ -ΝΗ- (C = 0)-or -NH- (C = 0) -NH-, G] shows a single bond, A3 shows ("((:) 〇Bivalent acyclic (B) A1 is-(CH2) 2- or (CH2) 3-, A2 is -NH- (C = 〇) -NH- (C = 0) · NΗ-, _NH_, or ≪: (= 〇). NH- and G 1 are groups other than a single bond. (54) 200526665 C} A is Cl ~ C6 divalent acyclic aliphatic hydrocarbon group, (ch2) 2- or-( CH2) ", a2 represents a single bond, and Ql is a heterocyclic group (but the heterocyclic group of G1 is a heterocyclic group of a monocyclic 1 to 6-membered ring representing $ to 6-membered ring, or A, G 2 Some are outside the table). (d) ^ is a bivalent non-cyclic aliphatic hydrocarbon group, (CH2) 2- or · (CH2) 3_, 8-2 shows a single bond other than a single bond, G is an aromatic hydrocarbon group, and C7 ~ C1G lipids which may be substituted Heterocyclic group substituted by cyclic hydrocarbon group (except when the aromatic hydrocarbon group of G 1 is phenyl group, or when the group is a single ring of five or six-membered ring, the phenyl group or five or six heterocyclic ring group of G 1 is substituted , Or A3-G2 part represents a hydrogen atom 0 (e) a divalent acyclic aliphatic hydrocarbon group, (CH2) 2- or-(CH2) 3-, A2 represents a single bond other than a single bond, A3 It is an irreplaceable (:! ~ (:! () Acyclic aliphatic 'G2 is a C5 ~ ClG aliphatic hydrocarbon group which can be substituted, which can be a group hydrocarbon group, or a heterocyclic group which can be substituted. (F ) A 1 shows C] ~ C 6 divalent acyclic aliphatic hydrocarbon group ': CH2) 2-, or-(Ch2) 3-, A2 shows other than a single bond, and G1 A3 shows an acyclic fat which can be substituted Group hydrocarbyl 'A4 is

) ...- C (= 0) -NR 丨 21-, -C (= S) -NR122-, -C) ...- 0-C (= 0)-, -NR] 25-C (= 0)-, -nr126_, -NR] 27-C (= 0) -〇-, -NR] 28-C (= 0) -NR] 29- c (= S) •, -NR] 3] -C (= S) -NR132-, -S-, -S (=

In particular, when-'is substituted, 5 of G1 <Specifically, hydrogen atom is represented by 1; 1 can be taken, or can be; heterocyclic ring of G1: other than the single ring section), especially-, Gi and A4 fatty acids The aromatic group of the hydrocarbon group is especially-(showing a single bond, showing -C (= 0: (= NR123 S (0) 2-, -NR) 30-: 0)-, _ S -59- (55) (55) 200526665 (= 0) 2-, -S (= 〇) 2-NR133 ... or-S (= 〇) 2-0-. In the above (d) to (f), A2 is -C (= 〇)- , -C (= 0) _ O-, -C (= 0) -NH-, -C (= 0) -NMe-, -NH-, -NH_C (= 〇)-, -NH-C (= 0 ) '-NH-C (= 〇) -NH- &gt; -NH-C (= 0) -NMe-, or -NH-C (= S)-When "W * -c (= 〇) -NH- , -NH ·, -NH-C (= 0)-, -NH-C (= 0) -0 ... or _NH-C (= 〇) · NH- is preferred. In the above formula (I), A5 is A single bond or a group bonded to a carbon atom of the pyrrole ring that binds R2 and a5 in the form of a carbon atom of R2-nr2 () 1-pyrrole ring (R20i represents a hydrogen atom or an acyclic aliphatic hydrocarbon group). A5 is the carbon atom of the pyrrole ring bonded to R2 and A5. When bonded as the carbon atom of R2-NR2G1-pyrrole ring, an example of the acyclic aliphatic hydrocarbon group of R2 ^ may be R 1 G with the above A2. The examples shown in Figure 1 are the same. The preferred examples of R 1 G2 are a hydrogen atom, methyl, ethyl, and propyl, especially a hydrogen atom and a methyl group. The preferred examples of A5 are single Bonds, -NH-, and -N (CH3)-, especially single bonds are preferred. R2 in the formula (I) may be a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, or may be substituted. Acyclic aliphatic hydrocarbon group, C3 ~ C8 alicyclic hydrocarbon group which can be substituted, C6 ~ C14 aromatic hydrocarbon group which can be substituted, or 1 ~ 4 selected from oxygen atom and nitrogen atom in the ring which can be substituted ' A heterocyclic group of an atomic group formed by a sulfur atom. A fluorine atom, a chlorine atom, a bromine atom, and an iodine atom of R2 in the above formula (I) are preferably a chlorine atom and a bromine atom. In the above formula (I), R2 is (:! ~ 0] which can be substituted. When the acyclic aliphatic-60- (56) (56) 200526665 group hydrocarbon group, the example of the acyclic aliphatic group may be the same as the example of the acyclic aliphatic hydrocarbon group of G2 above. The same is shown. Preferred examples of the C ^ Cio acyclic aliphatic hydrocarbon group of 112 are methyl, ethyl, isopropyl, butyl, isobutyl, third butyl, third pentyl, ethylene Base, 2-C Alkenyl, 2-methylpropyl and 2-propargyl. The substituent of the acyclic aliphatic hydrocarbon group which may be substituted for R2 may be a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a Cl ~ C7 alkyloxy group, a C6 ~ CiG square oxygen group, C7 which may be substituted ~ C9 aryloxy, C2 ~ C7Coxy, keto, CrC6 alkylsulfonyloxy, C2 ~ c7 醯 yl which can be substituted, carboxyl group, (: 2 ~ (: 7alkoxycarbonyl group, aminomethyl) Fluorenyl, c2 ~ c7 ^ amino carbamoyl, amine groups that can be substituted, alkamino groups that can be substituted, C2 ~ C7 amine groups that can be substituted, C2 ~ C8 alkoxycarbonylamino groups, C ] ~ C6 alkylsulfonylamino, cyano, nitro, Cl ~ C6 alkylsulfanyl, Cl ~ C6 alkylsulfinyl, Ci ~ C6 alkylsulfonyl, sulfamoyl, C ^ c6 alkylsulfanyl Fluorenyl group, sulfonic acid group, c3 ~ c6 alicyclic hydrocarbon group which may be substituted, and CrC6 acyclic aliphatic hydrocarbon group which may be substituted, aromatic hydrocarbon group which may be substituted, and heterocyclic group which may be substituted ( The ring has one to four substituents selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom). The substituent of the acyclic aliphatic hydrocarbon group which may be substituted for R2 is specific Example with the above G The substituents of the C ^ Cio alicyclic hydrocarbon group which may be substituted are the same as those shown in the specific examples.

Specific examples of the substituents of the substituted acyclic aliphatic hydrocarbon group of R2 are oxy group, C2 to C7 fluorenyl group, C2 to C7 fluorenylaminomethyl group, alkylamino group, C2 to C7 fluorino group, C3 ~ C6 alicyclic hydrocarbon group, and CrQ -61-(57) 200526665 acyclic hydrocarbon group, hydroxyl group, isobutoxyoxy group, etc. C] ~ (, methylamyl, butanyl, pentamyl ,,, Isobutoxycarbonyl, N-methylformamyl, N-, N-propylamine, N-cyclopropylalkylamine formamyl, dimethylamine, N-methylisoamine, 1 Hydrogen radicals and thio-aminyl groups, formamidine and pentamidine groups, amido groups, nitrates, isobutyl groups, and trifluoro groups are more acceptable (fluorine atom, chlorine atom, bromine Atoms, Protomethoxy, Ethoxy, Propoxy, Isopropoxy, Butoxy, First Butoxy, Third Butoxy, Pentoxy, and Cyclo-6oxy, Methyl With methylmethyloxy, 2.methoxyethoxy difluorinated ethylfluorenyl, ethyldonyl, propanyl, butylfluorenyl, isofluorenyl, isopentyl, etc. C2 ~ C7fluorenyl, keto, Residues, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl C2 ~ c, such as butoxy end group and second butoxycarbonyl group, oxycarbonyl group, carbamate, carbamate, N, N-dimethylamine carbamate, N_ethylamine ethyl-N- Methylamine formamyl, N, N-diethylaminomethylformamyl, N-isopropylamineformamyl, N-butylaminoformamylaminoformamyl, and N-cyclopropyl Methylmethylaminomethylamino, etc. (32 ~ (: 7 groups, amino groups, methylamino groups, ethylamino groups, propylamino groups, isopropylamino groups, N-ethylmethylamino groups, diethylamino groups, N-formyl groups) Propylpropylaminopropylamino, cyclopropylamino, cyclopropylmethylamino, etc. (:! ~ &Lt;: 6-alkrolidinyl, hexahydropyridyl, 4-methylhexahydropyridyl, N _ and? Fluorolinyl and other rings having 1 to 2 C4 ~ C6 cyclic amino groups selected from the group consisting of oxygen atoms and nitrogen groups, acetamidotrifluoride, acetamidoamino, propylamidoamine, butylamine Alkylamino groups such as amidino group and isobutylammonium group, methylsulfonamido groups, alkylsulfonyl groups such as ethylpropylsulfonamido group and butylsulfonamido group, cyano, methyl, ethyl , Propyl, isopropyl, butyl second butyl and third butyl, etc. (^ ~ alkyl, trifluoromethylated methoxy group -62- (58) 200526665 in the above formula (i), when R2 is a C3 ~ c8 alicyclic hydrocarbon group which may be substituted, the C3 ~ C8 alicyclic hydrocarbon group of R2 Examples may be the same as those shown in the C3 ~ C8 aliphatic hydrocarbon group of the above 02. Preferred examples of the C 3 ~ c 8 aliphatic hydrocarbon group of R 2 are cyclopropyl, cyclobutyl, cyclopentyl, and cyclo Hexyl, of which cyclopropyl is preferred

The substituents of C3 ~ C8 alicyclic hydrocarbon group substituted by R2 may be from fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxyl group, alkoxy group which may be substituted, c6 ~ c1G aryloxy group, c7 ~ C9 Aralkyloxy, C2 ~ c7 fluorenyloxy, keto, alkylsulfonyloxy, C2 ~ C7 fluorenyl, carboxyl, c2 ~ c7 alkoxycarbonyl, carbamoyl 'can be substituted C2 ~ C7 alkylamine formamidine group, amine group, CrC6 alkylamine group which can be substituted, which can be substituted (: 2 ~ (: 7 amine group, C2 ~ C8 oxamine amine group, Ci ~ C6) Mining Amine Group, Aromatic Group, Nitro, Cl ~ C6 Compound Sulfuric Group, Cl ~ C6 Compound Subspreading Group, Cl ~ C6 Compound Mining Group, Amine Sulfonyl, C] ~ C6 Alkylamine Sulfonyl, Sulfonic acid group, c3 ~ (: 6 alicyclic hydrocarbon group that can be substituted, and c Γ ~ C 6 acyclic aliphatic hydrocarbon group that can be substituted, and C6 ~ Cm aromatic hydrocarbon group that can be substituted, and can be substituted Heterocyclyl (having 1 to 4 atomic groups selected from oxygen, nitrogen, and sulfur atoms in the ring) selected from one or more substituents. The substituted C3 to C8 alicyclic ring of R2 Specific examples of substituents of formula The substitution of the substituted acyclic aliphatic hydrocarbon group of G2 is the same as that shown in the stomach system. The substituted group of the substituted C3 ~ C8 alicyclic hydrocarbon group of R2 may be a oxo group and a C2 ~ C? Group. , C2 ~ C7 alkylaminomethyl, C] ~ C6 alkylamino-63-i (59) (59) 200526665, C2 ~ C7 alkylamino, c3 ~ C6 alicyclic hydrocarbon group, and acyclic fat Group hydrocarbon groups, C6 to C14 aromatic hydrocarbon groups, and heterocyclic groups (with 1 to 4 atomic groups selected from oxygen, nitrogen, and sulfur atoms in the ring) can also be used (fluorine, chlorine, bromine Atom, iodine atom, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, second butoxy'th. Tributoxy, pentyloxy, And cyclopropoxy, etc. (^ ~ (^ alkoxy, methoxymethyloxy, 2-methoxyethoxy, formamyl, triethyl fluoride, ethenyl, propionyl) , Butanyl, isobutylfluorenyl, pentamyl, isopentamyl, etc. C2 ~ c7fluorenyl, keto, carboxyl, methoxycarbonyl, ethoxycarbonyl, propoxy-, isopropyloxycarbonyl, butoxycarbonyl, isobutyl C2 such as oxycarbonyl and tertiary butoxy C7 alkoxycarbonyl, carbamoyl, N-methylaminomethyl, N, N-dimethylaminomethyl, N-ethylaminomethyl, N-ethyl-N-methylamine Methyl methyl, N, N-diethylamine methylamino, N-propylaminomethylmethyl, N-isopropylaminomethylmethyl, N-butylaminomethylmethyl, N-cyclopropylamine C2 ~ C7 alkylamines such as methylamino and N-cyclopropylmethylamine methylamidino, methylamine, methylamine, methylamino, ethylamino, propylamino, isopropylamine, dimethylamino, C ^ C6 alkylamino groups such as N-ethylmethylamino 'diethylamino, N-methylpropylamino, N-methylisopropylamino, cyclopropylamino and cyclopropylmethylamino, 1-pyrrolidine Group, hexahydroorphinyl group, 4-methyl /, chlorosulfonyl, N-hexachloro D [^ B amidinyl group and morpholinyl group, etc. have 1 to 2 selected from the group consisting of an oxygen atom, a nitrogen atom and C4 ~ C6 cyclic amine group, sulfur trifluoride acetamidoamine group, formamidine group, acetamido group, diamine group, butylamino group, isobutylamino group and pentyl group醯 Amino group and so on C] ~ C7 醯 Amino group 'methylsulfonamido group, ethyl sulfonamido group, propylsulfonase S female group and butyl sulfonium group_ C 1 ~ C6 Alkyl, nitro, cyano-64-(60) (60) 200526665, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second butyl, and third butyl alkyl groups One or more substituents selected from the group consisting of methyl trifluoride, methyl trifluoride, and trifluoromethoxy. When R2 in the above formula (I) is a c6 to c14 aromatic hydrocarbon group which may be substituted, examples of the C6 to Cm aromatic hydrocarbon group of R2 may be the same as those shown in the example of the C6 to C14 aromatic hydrocarbon group of G2 described above. A preferable example of the C 6 to C µ aromatic hydrocarbon group of R 2 is a phenyl group. The substituent of the substituted C6 ~ Cm aromatic hydrocarbon group of R2 may be a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, an alkyl group, a Cl ~ C7 alkoxy group, C6 ~ CiQ aryloxy group which may be substituted , C7 ~ C9 aramoxy, c2 ~ C7 alkoxy 'keto, C! ~ C6 alkylsulfonyl oxy, c2 ~ C7 fluorenyl, carboxyl, C2 ~ C7 alkoxycarbonyl, amine which can be substituted Formamidine, C2 ~ C7 alkylamine methylamine which may be substituted, amine group, alkylamine amino group which may be substituted, C2 ~ c7 methylamine group which may be substituted, c2 ~ c8 alkoxycarbonylamino group, c ] ~ C6 Alkylsulfonamido, cyano, nitro, hydrazone! ~ (: 6 alkylthio group, CrC6 alkylsulfinyl group, (^ ~ (: 6 alkylsulfonyl group, amine sulfonyl group, alkylamine sulfonyl group, sulfonate group, c3 ~ C6 alicyclic ring which can be substituted) Formula hydrocarbon group, which can be substituted (^ ~ 06 acyclic aliphatic hydrocarbon group, which can be substituted 4 aromatic hydrocarbon group, and which can be substituted heterocyclic group (having 1 to 4 selected from oxygen atom and nitrogen atom in the ring) , And an atomic group formed by a sulfur atom) selected from one or more substituents. Among them, an alkyl group, 〇 ~~ (: 6 alkoxy group, fluorine atom, and chlorine atom are preferred. The R2 is substituted Specific examples of the substituents of C6 to C! 4 aromatic hydrocarbon groups are the same as those shown in the specific examples of the substituted C of G2 to C1G acyclic aliphatic hydrocarbon groups. -65- (61) (61) 200526665 Ci ~ c7 alkoxy, C2 ~ C7 fluorenyl, C ~ C7 alkoxy, C2 ~ C7 aryl, C2 ~ C6 amine, C2 ~ C醯 Amine group, C3 ~ C6 alicyclic hydrocarbon group, C] ~ C6 acyclic hydrocarbon group, C] ~ 06 acyclic aliphatic hydrocarbon group, Ce ~ C 14 aromatic hydrocarbon group and heterocyclic group (1 ~ 4 selected from the group consisting of oxygen source , And atomic groups formed by sulfur atoms) can be more. (Fluorine, chlorine, bromine, hydrogen, hydroxy, methoxy, ethoxy, propoxy, isopropoxy, butoxy, Isobutoxy, second butoxy, third butoxy, pentyloxy, and cyclopropoxy, such as alkoxy, methoxymethyloxy, 2-methoxyethoxy, formamidine C2 ~ C7fluorenyl, keto, carboxyl, methoxycarbonyl, ethoxycarbonyl, etc. C2 ~ C, such as propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl 'isobutoxycarbonyl, and tertiary butoxymine &lt; 7 oxonyl group, carbamate group, N · methylamine carbamate group, N, N-dimethylamine carbamate group, N-ethylamine carbamate group, N-ethyl-N-formamidine Methylaminomethane, N, N-diethylaminomethane, N-propylaminomethane, N-isopropylaminemethane, N-butylaminomethane, cyclopropylamine C 2 ~ C7 alkylamines such as methylamino and N-cyclopropylmethylaminomethylamido, methylamino, methylamino, ethylamino, propylamino, isopropylamino, dimethylamino , N-ethylmethylamino, diethylamino, N · methylpropylamino, methylisopropylamino, cyclopropylamino, and cyclopropylmethylamino, etc. Ci-Cs amine groups, i_D [troπ Anthyl, hexahydropyridyl, 4-methylhexahydropyridyl D well group, N-hexahydropyridyl and morpholinyl have 1 to 2 rings selected from oxygen, nitrogen and sulfur atoms in the ring. C4 ~ C6 cyclic amino group, acetamido trifluoride, formamidine, acetamido, propylamino, butylamino, isobutylamido, and pentamidine -66- (62) (62) 200526665 and other C] ~ C 7 sulfonylamino, methylsulfonamido, ethylsulfonamido, propylsulfonamido, and butylsulfonamido C] ~ c 6 alkylsulfonamido, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second butyl, and dibutyl etc. Ci ~ C6 courtyard group, trifluoromethyl group and trifluoromethoxy group selected by one or more substituents). When R2 in the formula (I) is a heterocyclic group having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring which may be substituted, an example of the heterocyclic group of R2 may be The examples of the heterocyclic group of G2 are the same. The heterocyclic group of R2 is bonded to A5 on a carbon atom or a nitrogen atom. Preferred examples of the heterocyclic group bonded to A5 at the carbon atom may be furyl, thienyl, pyrrolyl, pyrazolyl, humazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyridine Pyridyl, pyrimidinyl, pyridinyl, daphnyl, benzofuranyl, indolyl, benzothienyl, quinolinyl, isoquinolinyl, quinazolinyl, benzimidazolyl, and benzohumazole In the ring such as a group, there are 1 to 3 monocyclic or cyclic C3 to C9 aromatic heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. Preferred bases are 2-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 2-imidazolyl, 5-imidazolyl, 4-pyrazolyl, 2-Dfazolyl, 5-humazole , 5-isothiazolyl, 2-thiazolyl, 5-thiazolyl, 5-isothiazolyl, 3-isothiazolyl, 2-pyridyl, 2-pyrimidyl, 2-benzofuranyl, and 2- The benzothienyl group and the like have 1 to 2 monocyclic or bicyclic C3 to C9 aromatic heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. Among them, the most preferable base ring has 1 to 2 monocyclic C3 to C5 aromatic heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. Among them, 2-furanyl, 2-thienyl, 2-pyrrolyl, 2-67- (63) (63) 200526665 pyridyl, and 4-pyrazolyl are preferred. On the other hand, a preferable example of a heterocyclic group having 1 to 4 heterocyclic groups selected from an oxygen atom, a nitrogen atom, and a sulfur atom in a ring bonded to A 5 on a nitrogen atom is a 1-pyrazolyl group, Bimizolyl, 1-pyrrolidinyl, N-hexahydropyridyl, morpholinyl, 1-hexahydropyridyl, and 1-hexahydropyridyl. A heterocyclic group having 1 to 4 atomic groups selected from an oxygen atom, a nitrogen atom, and a sulfur atom in the ring of R2 is a single bond when A5 is bonded to a nitrogen atom. The substituted ring of R2 has 1 to 4 substituents selected from the heterocyclic group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. The substituent is a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, Substituted C! ~ C 7 alkoxy, C6 ~ C1G aryloxy, C7 ~ C9 aralkyloxy, C2 ~ C7 alkoxy, keto, (^ ~ 0: 6 alkanesulfonyloxy, can be Substituted C2 ~ C7 alkyl groups, carboxyl groups, C2 ~ C7 alkoxycarbonyl groups, carbamoyl groups, C2 ~ C7 alkylaminomethyl groups which can be substituted, amine groups, C which can be substituted] ~ C6 alkylamino groups C2 ~ C7 fluorenylamino, C2 ~ C8 alkoxycarbonylamino, alkanesulfonamido, cyano, nitro, alkylthio, (^ ~ (: 6 alkylsulfinyl sulfenyl, D-Alkanesulfonyl, amidino-sulfonyl, alkylaminosulfonyl, sulfonate, c3 ~ c6 alicyclic hydrocarbon groups that can be substituted, and (^ ~ cardiac acyclic aliphatic Hydrocarbon group, C6 ~ c14 aromatic hydrocarbon group which can be substituted, and heterocyclic group which can be substituted (having 1 to 4 atoms selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom in the ring) More than one substituent. The R2 Specific examples of the substituent having a heterocyclic group selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the substituted ring are the substituents of the substituted acyclic aliphatic hydrocarbon group of the above G2 Specific examples are shown in -68- (64) (64) 200526665. The substituted ring of R2 has a substitution of ~ 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. C] ~ C7 alkoxy, C2 ~ C7 fluorenyl, C2 ~ C7 alkylaminomethyl, Cl ~ C6 alkamino, C2 ~ C7 amine, C3 ~ C6 aliphatic hydrocarbon, c] ~ C6 acyclic aliphatic hydrocarbon group and C6 ~ cM aromatic hydrocarbon group and heterocyclic group (with ι ~ 4 selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom in the ring) can be further modified (fluorine atom, Chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, second butoxy, third butoxy, pentyl Oxygen, and cyclopropoxy, etc. (^ ~ (: 6 alkoxy, methoxymethyloxy, 2-methoxyethoxy 'formamyl, trifluoride ethenyl, ethenyl) , Propionyl, Fluorenyl, isobutylfluorenyl, pentamyl, isopentyl, etc. c2 ~ c7 fluorenyl, keto, carboxyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxy Carbonyl and tertiary butoxycarbonyl groups, such as C2 ~ C7, oxymethyl, carbamoyl, N-methylaminomethyl, N, N-dimethylaminomethyl, N-ethylaminomethyl , N-ethyl-N-methylaminomethylmethyl, N, N-diethylaminomethylmethyl, N-propylaminomethylmethyl, N-isopropylaminomethylmethyl, N-butyl C2 ~ C7 alkylamine methylamine, amino, methylamino, ethylamino, propylamine, N-cyclopropylaminomethylmethyl, and N-cyclopropylmethylaminomethylmethyl Methyl, isopropylamino, dimethylamino, N-ethylmethylamino, diethylamino, N-methylpropylamino, N-methylisopropylamino, cyclopropylamino, and cyclopropylmethylamino C 1 ~ C 6 amine group, 1-sullopyridinyl 'hexahydropyrrolyl, 4-methylhexahydropyridyl, N-hexahydropyridyl and morpholinyl have 1 to -69- (65) (65) 200526665 C4 ~ C6 cyclic amine group selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom, Cl ~ c7 fluorenylamine, methylsulfonylamine, and other fluorinated amines, methylformamide, acetamide, propylamino, butylamino, isobutylamino, and pentamidine, etc. C i ~ C6 alkylsulfonamido, nitro, cyano, methyl, ethyl, propyl, isopropyl One or more substituents selected from the group consisting of C ^ C6 alkyl such as propyl, butyl, isobutyl, second butyl, and third butyl, methyl trifluoride, and trifluoromethoxy group) . As the substituent of R2 of the present invention, 1 to 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the ring which can be substituted are exemplified. The preferred substituent is fluorine. Atom, chlorine atom, bromine atom, iodine atom, hydroxyl group, cyano group, nitro group, amine group, methylamino group, ethylamino group, propylamino group, isopropylamine group, butylamine group, isobutylamine group, Second butylamino, third butylamino, pentylamino, hexylamine, dimethylamino, N-ethylmethylamino, diethylamino, N-methylpropylamino, N-methylisopropyl Linear or branched chains such as propylamino, N-methylbutylamino, N-methyl tertiarybutylamino, N-ethylisopropylamino, dipropylamino, diisopropylamino, and ethylbutylamino C ^ C 6 —or dialkylamino, carboxyl, substituted methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second butyl Saturated, tributyl, pentyl, isopentyl, neopentyl, tertiary pentyl, hexyl, isohexyl, methylpentyl, and 1-ethylbutyl &lt; ^ ~ 0: 6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, etc. C3 ~ C6 alicyclic hydrocarbon groups, optionally substituted methoxy, ethoxy, propoxy, Isopropoxy, butoxy, isobutoxy, second butoxy, third butoxy, pentyloxy, isopentyloxy, neopentyloxy, tertiary pentoxy and hexyloxy, etc. C! ~ C6 alkoxy group formed by a linear or branched alkyl group and -70- (66) (66) 200526665 oxy group, ethyl ethenyl, propionyl, butyl fluorenyl, isobutyl fluorenyl, trimethyl C2 to C7, such as methyl ethylfluorenyl and hexamethylene, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, second butylthio, Tertiary butylthio, pentylthio, and hexylthio, etc. Cl ~ C6 thio, methyl trifluoride, trifluoromethoxy, acetylamino, propylamino, butyl C2 ~ C7 amidino groups such as fluorenylamino, isobutyramine, trishenylacetamido, and hexamethyleneamine, and Nβ methylaminoformamyl, N-ethylaminomethyl which can be substituted Fluorenyl, N-propylaminomethylmethyl, N-propylaminomethylmethyl, N-butylaminomethylmethyl, N- Butylaminomethane, second butylaminomethane, N-pentylaminomethane, N, N-dimethylaminomethane, N-ethyl-N-methylaminomethane And C2 ~ C7 alkylamine formyl groups formed by linear or branched alkyl groups such as N, N-diylaminomethyl and carbamoyl groups. The substituted ring of R2 has 1 to 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom +, and a sulfur atom. Preferred examples are a fluorine atom, a chlorine atom, a bromine atom, and a C2 to C4 fluorenyl group. , A hydroxyl group, a carboxyl group, an alkoxycarbonyl group, an alkyl group that may be substituted, a hydroxyl group, and a CrQ alkoxy group that may be substituted. The preferred combination of R2 and A5 in the above formula (1) is explained here. In the present invention, in the combination of R2 and A5 of the formula (I), when R2 is a fluorine atom, a chlorine atom, or an iodine atom, A5 represents a single bond. In the present invention, the combination of R2 and A5 of the above formula (I) is that A5 is a single bond and R2 is a substitutable (:! ~ &lt;:! () Acyclic aliphatic hydrocarbon group, C 6 ~ μ aromatic hydrocarbon group which may be substituted, or heterocyclic group which may be substituted, especially a5 is a single bond and R2 is (:) ~ ( : 〇 Acyclic aliphatic hydrocarbon group, C3 ~ C 8 alicyclic smoke-71-(67) (67) 200526665 group, phenyl group which can be substituted, or 1 ~ 2 options in the ring which can be substituted A combination of a heterocyclic group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom is preferable. Among them, R2 is particularly shown as cyclopropyl, cyclobutyl, cyclopropylmethyl, methyl, ethyl, and ethylene. It is suitable for isopropyl, isopropyl, isobutyl, or 2-methyl-1-propenyl, and A5 is a single bond, and R2 is a alkoxy group, Cl ~ C4 alkoxy group, and C2 ~ C4 fluorenyl, hydroxy, carboxyl, alkoxycarbonyl, fluorine, or any or a plurality of substituted thiophene, pyridyl, furyl, pyrrolyl, pyrazolyl, or phenyl groups of a chlorine salt are also suitable In addition, a combination of -NR2 () 1- and A2 in A5 which represent a hydrogen atom or an acyclic aliphatic hydrocarbon group which may be substituted is also preferable. In the above formula (I), A6 represents a single bond, or R3 and Carbon atom of pyrrole ring bound to A6 R3-NR3 () 1-pyrrole ring, R9-C (= 0), pyrrole ring, R3-NR302-C (= 〇) -D than pyrrole ring, R3-NR303-C (= S) -pyrrole ring, R3-NR3 () 4_C (= 〇) -NR3G5-pyrrole ring, R3-C (= 0) -NR306-pyrrole ring, R3-NR307-CH = N-role ring, R3-C (= 0) -〇 -Pyrrole ring, R3-〇-C (= 〇) -pyrrole ring, R3-0-pyrrole ring, R3-S-pyrrole ring, R3-S (= 0) -pyrrole ring, R3-S (= 0) 2 -Pyrrole ring, R3-CR308 = CR309-pyrrole ring, r3-CeC-pyrrole ring, or R3-S (= 0) 2-C tri-C-pyrrole ring in the form of a bond (... ㈡ to R3 09 are respectively Independently shown hydrogen atom or Cl ~ C4 acyclic aliphatic hydrocarbon group). When r3 and carbon atom of pyrrole ring are bonded as carbon atom of R3-NR3G1 pyrrole ring, 'R3 (Ci ~ C4 acyclic aliphatic hydrocarbon group of n Examples may be the same as those shown for the above-mentioned examples of R 1G1 of A2. The preferred examples of R3 G 1 are hydrogen atom -72- (68) (68) 200526665, methyl and ethyl, especially hydrogen atom. When the carbon atom of R3 and the pyrrole ring is bonded as the carbon atom of r3-nr3G2-c (= 0) -pyrrole ring, an example of the acyclic aliphatic hydrocarbon group of R3G2 may be the same as R1 of A2 ( Example phase of n Were Preferably R3 embodiments of the system a hydrogen atom, methyl and ethyl, particularly preferably a hydrogen atom. 1 ^ 3 of the pyrrole ring with the carbon atoms to 113 ^ 113 () 3- &lt;: When the carbon atom form of the (^)-pyrrole ring is bonded, examples of the acyclic aliphatic hydrocarbon group of R3 () 3 may be the same as those shown in the above-mentioned example of R1G1 of A2. Preferred examples of the R3G3 are a hydrogen atom, a methyl group and an ethyl group, and a hydrogen atom is particularly preferred. When the carbon atom of R3 and the pyrrole ring is bonded as the carbon atom of r3-nr3G4-c (= 0) -nr3G5-pyrrole ring, the c! ~ C4 acyclic aliphatic hydrocarbon group of R3G4 and R3G5 can be exemplified as The examples of R 1 G 1 of A 2 described above are the same. Preferred examples of the R3C) 4 and R3G5 are a hydrogen atom, a methyl group and an ethyl group, and a hydrogen atom is particularly preferred. When R3 and the carbon atom of the pyrrole ring are bonded in the form of R3_ (c = 0) -NR3G and the carbon atom of the pyrrole ring, an example of the acyclic aliphatic hydrocarbon group of R3 062 Cl to c4 may be the same as R1 of A2 ( ) 1 shows the same example. Preferred examples of the R3G6 are a nitrogen atom, a methyl group and an ethyl group, and a hydrogen atom is particularly preferred. In the case where the carbon atom of the role ring is bonded as the carbon atom of the-^^^ 彳 ^^ pyrrole ring, the example of R3072 Cl ~ c4 acyclic aliphatic hydrocarbon group may be the same as the example of A2 above. Shown the same. Preferred examples of this R307 are a chlorine atom, a methyl group, and an ethyl group, and a methyl group is particularly preferred. When the carbon atom of R3 and the pyrrole ring is bonded in the form of r3_cr3g8-CRm and the carbon atom of the pyrrole ring, C of R3G8 and R3G9] ~ C4 (69) (69) 200526665 of the acyclic aliphatic hydrocarbon group can be combined with The above example of R1G1 of A2 shows the same. In the formula (I), R3 represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a nitro group, or a substituted C! ~ C! 〇 Acyclic saturated aliphatic hydrocarbon group, or a substituted C3 ~ C8 alicyclic hydrocarbon group, C 6 ~ Ci 4 aromatic hydrocarbon group which may be substituted, heterocyclic group having 1 to 4 atomic groups selected from oxygen atom, nitrogen atom, and sulfur atom in the ring which may be substituted. In the formula (I), R3 is preferably a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom, preferably a chlorine atom, a bromine atom, and an iodine atom. When R3 in the above formula (I) is an acyclic saturated aliphatic hydrocarbon group which can be substituted, examples of the acyclic saturated aliphatic hydrocarbon group are methyl, ethyl, propyl, isopropyl'butyl, iso Butyl, second butyl, third butyl, pentyl, isopentyl, neopentyl, third pentyl '2-methylpentyl, 4-methylpentyl, 丨 -ethylbutyl, Alkyl groups such as hexyl, heptyl, 2-methylhexyl, 5-methylhexyl, 1'h dimethylpentyl, 6-methylheptyl, octyl, nonyl, and decyl. The 113C] ~ (:! 〇 A preferable example of the acyclic aliphatic hydrocarbon group is a methyl group, an ethyl group, an isopropyl group, a butyl group, a third butyl group, and a third pentyl group. R3 is substituted ( :! ~ 〇! 〇 The substituent of the acyclic saturated aliphatic hydrocarbon group may be a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a C! ~ C7 alkoxy group, C6 ~ ClG aryloxy group which may be substituted. , C7 ~ C9 aralkyloxy, C2 ~ C7 donkeyoxy, keto, C2 ~ C7 fluorenyl which can be substituted, C2 ~ C7 alkoxycarbonyl, carbamoyl, C = 2 ~ C7 Alkylamine methylamine, amine, K6 alkylamine which can be substituted, c2 ~ c7 methylamine which can be substituted, C2 ~ (: 8 alkoxycarbonylamino, C ^ C: 6 alkylsulfonamide Group, cyano group, nitro group, Ci ~ C6 alkylthio group, c! ~ C6 alkylsulfinylfluorenyl group, c3 ~ c6 alicyclic hydrocarbon group which may be substituted, may be substituted by -74- (70) (70) 200526665 Non-cyclic aliphatic hydrocarbon group, c6 ~ c14 aromatic hydrocarbon group which can be substituted, and heterocyclic group which can be substituted (the ring has 1 to 4 atom groups selected from oxygen atom, nitrogen atom, and sulfur atom ) More than one substituent selected from the group. The R3 Specific examples of the substituent of the substituted 0 acyclic saturated aliphatic hydrocarbon group are the same as the specific examples of the substituent of the acyclic aliphatic hydrocarbon group which may be substituted in the above G2. The substituted acyclic of R3 Substituents for saturated aliphatic hydrocarbon groups, alkoxy groups, c2 to c7 fluorenyl groups, c2 to C7 alkylamine fluorenyl groups, K6 alkylamine groups, C 2 to C 7 fluorenylamine groups, C 3 to C 6 alicyclic hydrocarbon groups , C] ~ C 6 acyclic hydrocarbon group, Ci ~ C1G acyclic aliphatic hydrocarbon group, c6 ~ C14 aromatic hydrocarbon group, and heterocyclic group (with 1 to 4 members selected from oxygen atom, nitrogen atom, and sulfur in the ring The atomic group formed by the atom) can be further modified by (fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy'isopropoxy, butoxy, isobutoxy , C-C6 alkoxy, methyl-butoxy, tertiary butoxy, pentyloxy, and cyclopropoxy, methoxymethyloxy, 2-methoxyethoxy, formamyl , Trifluoride ethenyl, ethenyl, propionyl, butyl fluorenyl, isobutyl fluorenyl, pentyl fluorenyl and isopentyl fluorenyl, etc. C2 ~ C7 alkoxycarbonyl groups such as carbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl and tertiary butoxycarbonyl, carbamoyl, N-methylaminomethyl, N, N-dimethyl Carbamate, N-ethylcarbamate, N-ethyl-N-methylcarbamate, n, N-diethylcarbamate, N-propylcarbamate, N -Isopropylamine formamyl, butylaminoformamyl, N-cyclopropylaminoformamyl, and N-cyclopropylmethylaminoformamyl etc. 02 ~ (: 7 -75- (71 200526665 Alkylaminomethyl, amino, dimethylamino, N-ethyl, N-methylisopropylamino, amino, b-pyrrolidinyl, hexahydropyridyl, and morpholine atoms and sulfur atoms The resulting groups of sulfonamido, methylamido, acetamido, and pentamido, sulfoamido, propylsulfoamido, nitro, cyano, isobutyl, second butyl, and In the above formula (I), the same as those shown in the examples of C3 to C8 alicyclic hydrocarbon groups of R2 are cyclopropyl, cyclobutyl, and substituted C3 protons and chlorine of R3. Atom, bromine atom, alkoxy, C6 ~ C1G aryloxy; C2 ~ C7 醯 3 which can be substituted, C2 ~ which can be substituted c7 CrQ alkylamino, can be eryl, cyano, nitro, can, methylamino, ethylamino, propylamino, isopropylaminomethylamino, diethylamino, N-methylpropylaminocyclopropylamine C1- ~ 6-alkanehexahydropyridyl, 4-methylhexahydropyridyl, N-yl and other groups having 1 to 2 selected from oxygen and nitrogen atoms in the ring C4 ~ cyclic amine group, acetamido trifluoride group, propylamino group, butylamino group, isobutyl group &lt; ^ ~ (: Ci ~ C6 alkylsulfonyl, methyl, ethyl, propyl, isopropyl, etc. Butyl, and second butyl, such as C ~~ C6, molybdenum, trifluoride group selected by one or more substituents) R3 is a C3 ~ C8 alicyclic hydrocarbon group which can be substituted [the example of the group may be C3 ~ C8 fat type with the above G2. Preferred examples of the C3 to C8 aliphatic hydrocarbon group of R2 are cyclopentyl and cyclohexyl. The substituent of ~ C 8 alicyclic hydrocarbon group may be self-fluorination, iodine atom, hydroxyl group, substitutable group, C7 ~ C9 aralkoxy group, c2 ~ C7 alkoxy group,; carboxyl group, C2 ~ C7 alkane group Oxycarbonyl, carbamoylamine, carbamoyl, amine, C2 ~ C? Amine, which can be substituted, 〇: 2 ~ 〇8 alkoxycarbonylamine substituted C3 ~ C6 alicyclic Formula hydrocarbon group, non-cyclic aliphatic hydrocarbon group which can be taken as -76- (72) (72) 200526665 and C6 ~ c14 aromatic hydrocarbon group which can be substituted and heterocyclic group which can be substituted (with 1 ~ 4 in the ring) ~~ substituents selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom). Specific examples of the substituents of the substituted C3 to C8 alicyclic hydrocarbon group of R3 are the same as the specific examples of the substituents of the substituted C! To C! G2 of the acyclic aliphatic hydrocarbon group described above. The substituted C3 ~ C8 alicyclic hydrocarbon group of R3 may be Cl ~ c7 alkoxy, C2 ~ C7 fluorenyl, C2 ~ C7 alkylaminomethyl, C! ~ C6 amine, C2 ~ C7 amine group, C3 ~ C6 alicyclic hydrocarbon group, and CrQ acyclic aliphatic aziridinyl group, C6 ~ Cm scented nicotinyl group, and heterocyclic group (with 1 ~ 4 selected from oxygen atom, nitrogen in the ring Atoms and atomic groups formed by sulfur atoms) can be further modified by (fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, Isobutoxy, second butoxy, di-butoxy, pentyloxy, and cyclopropoxy% = Ci ~ C6 alkyloxy, methoxymethyloxy, 2-methoxyethoxy C2 ~ C: 7-methyl, keto, carboxyl, methoxy, etc. C2 ~ C: 7-methyl, keto, carboxyl, methoxy, etc. C2 ~ c7 alkoxycarbonyl, carbamoyl, N · methylaminoformamyl, carbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl and tertiary butoxycarbonyl, etc. , N, N-dimethylamine formamyl, N- Methylamine formamyl, N-ethyl-methylaminoformamyl, N, N-diethylamine formamyl, N-propylaminoformamyl, N-isopropylamine formamyl, N C2-C7 alkylamine formamidine, amine, methyl-77- (73 ) (73) 200526665 Amino, ethylamino, propylamino, isopropylamino, dimethylamino, N-ethylmethylamino, diethylamino, N-methylpropylamine, N-methylisopropylamine Cl, C6 alkylamino groups such as amino, cyclopropylamino, and cyclopropylmethylamino, 1-pyrrolidinyl, hexahydropyridyl, 4-methylhexahydropyridyl, N-hexahydropyridyl and others C4 ~ 06 cyclic amine groups, acetamidotrifluoride, formamidine, and acetamidine having 1 to 2 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring such as a phospholine group Group, propylamine, butylamino, isobutylamino, and pentamidine, etc. (^ ~ amine, methylsulfonamido, ethylsulfonamido, propylsulfonamido And butylsulfonylamino groups C] ~ C6 alkylsulfonylamino, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl , Isobutyl, second butyl, and third butyl groups such as C to C6 alkyl groups, trifluoro groups, and trifluorooxy groups selected from one or more substituents). In the case where 113 is a C6 to C14 aromatic hydrocarbon group which may be substituted, an example of the C6 to C14 aromatic hydrocarbon group of R3 may be the same as that shown in the above-mentioned example of the C6 to C14 aromatic hydrocarbon group of G2. The C of R3 A preferred example of the 6 to C14 aromatic hydrocarbon group is a phenyl group. The substituted C6 to C of the R3] 4 aromatic hydrocarbon group may be a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, or a substituted one. C, ~ C7 alkoxy, C6 ~ Cio aryloxy, C7 ~ C9 aryloxy, c2 ~ c7 fluorenyloxy, keto, alkylsulfonyloxy, C2 ~ C7 fluorenyl , Carboxyl, C2 ~ C7 alkoxycarbonyl, carbamoyl, C2 ~ C7 alkylaminomethyl which can be substituted, amine, Ci ~ C6 alkylamino which can be substituted, C2 ~ C7 which can be substituted Fluorenylamino, C 2 ~ C 8 oxonamine amine, C 1 ~ C 6 sulfonyl amine, cyano, nitro, C! ~ C6 alkylthio, sulfinyl sulfonyl, (^ ~ ( ^ Alkylsulfonyl, amine-78- (74) 200526665 , C ^ C: 6 alkylamine sulfonyl, sulfonic group, C3 ~ alicyclic hydrocarbon group which can be substituted, C ^ C6 acyclic aliphatic hydrocarbon group which can be substituted, C6 ~ Cm aromatic which can be substituted One or more substituents selected from the group consisting of a hydrocarbon group and a heterocyclic group which can be substituted (the ring has 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom). Specific examples of the substituent of the substituted C6 to Cm aromatic hydrocarbon group of R3 are the same as the specific examples of the substituent of the substituted acyclic aliphatic hydrocarbon group of G2 described above. The substituted C6 ~ μ aromatic hydrocarbon group substituents of R3 ^ ~ ... Hydroxy, C2 ~ C7, G2, C2 ~ C7, Fl female, Glyceryl, C2 ~ C7 Group, C3 ~ C6 alicyclic hydrocarbon group, c! ~ C 6 acyclic aliphatic hydrocarbon group, C6 ~ I4 aromatic hydrocarbon group and heterocyclic group (the ring has 1 to 4 selected from oxygen atom, nitrogen atom, and sulfur The atomic group formed by the atom) can be further modified by (fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy C ^ C6 alkoxy, second butoxy, third butoxy, pentyloxy, and cyclopropoxy, methoxymethyloxy, 2-methoxyethoxy, formamyl , Ethyl trifluoride, Ethyl fluorenyl®, Propyryl, Butyryl, Isobutylamyl, Pentamyl and Isoamyl, etc. C2 ~ C7 Amidino, Keto, Carboxyl, Methoxy, Ethoxycarbonyl C2 ~ C7 alkoxycarbonyl, carbamoyl, N-methylamine formamyl, N, propionyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl and tertiary butoxycarbonyl, etc. … Dimethylaminomethyl, N-ethylaminomethyl , N-ethyl · ν_methylaminomethylmethyl, N, N · diethylaminomethylmethyl ', N-propylaminomethylmethyl, N-isopropylaminomethylmethyl, N-butyl C 2 ~ C7 alkylamine methylamine, amines such as methylaminomethylmethyl, N-cyclopropylaminomethylmethyl, and 1-ring-79- (75) (75) 200526665 propylmethylaminomethylmethyl Methyl, methylamino, ethylamino, propylamino, isopropylamino, dimethylamino, N-ethylmethylamino, diethylamino, N-methylpropylamino, N-methylisopropylamine, Cyclopropylamino and cyclopropylmethylamino groups, such as C! ~ C, 6-amino groups, 1-D [t amidinyl group, hexahydro D ratio group, 4-methylhexahydropyridyl group, N-hexahydro C4 ~ C6 cyclic amino groups, acetamidotrifluoride, and formamidinyl groups having 1 to 2 atoms selected from the group consisting of oxygen, nitrogen and sulfur atoms in the ring such as pyridyl and morpholinyl , Acetamido, propylamido, butylamido, isobutylamido, and pentamido, etc. C! ~ C 7 amido, methylsulfonamido 'ethylsulfonamido, Ci ~ c6 fluorenyl ammonium, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl , An isobutyl group, a second of the groups selected butyl tert-butyl and like C ^ C6 alkyl, and methyl trifluoride trifluoride methoxy or more substituents) substituted. In the above formula (I), when R3 is a heterocyclic group having 1 to 4 selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring that may be substituted, R3 has 1 to 4 in the ring Examples of heterocyclic groups selected from the group consisting of oxygen, nitrogen, and sulfur atoms are heterocyclic rings having 1 to 4 atoms selected from the group consisting of oxygen, nitrogen, and sulfur atoms in the ring of G2. The base shows the same. The heterocyclic group having 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the ring of R3 is bonded to A6 on a carbon atom or a nitrogen atom, and bonded to A6 on a carbon atom. Preferred examples of the heterocyclic group having 1 to 4 selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the ring are an uranyl group, a thienyl group, a pyrrolyl group, a pyridyl group, an nf fluorenyl group, Isopropyl group, eg D group -80- (76) (76) 200526665, isothiazolyl, imidazolyl, pyridyl, pyrargyl, pyrimidinyl, tower 11 yl, benzofuranyl, indole Group, benzothienyl, D | Porphyrinyl, isoxolinyl, quinazolinyl, benzimidazolyl, and benzoxazolyl have 1 to 3 selected from the group consisting of an oxygen atom, a nitrogen atom, and A monocyclic or cyclic C3 ~ C9 aromatic heterocyclic group in an atomic group formed by a sulfur atom. Preferred bases are 2-pyranyl, sulfanyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 2-henazolyl, 2-thiazolyl, 2-pyridyl, 3-pyridyl , 4-pyridyl, 2-N-hydroxypyridyl, 3-N-hydroxypyridyl, 4-N-hydroxypyridyl, 3-pyrazolyl, cardiac pyrazolyl, 4-imidazolyl, 2-pyrimidine And 5-pyrimidinyl are preferred. On the other hand, a preferable example of a heterocyclic group having 1 to 4 heterocyclic groups selected from an oxygen atom, a nitrogen atom, and a sulfur atom in a ring bonded to A6 on a nitrogen atom is 1-imidazolyl, 1- Pyrazolyl, 1-pyrrolidinyl, pyrrolidinyl, N-hexahydropyridyl, morpholinyl, 1-hexahydropyridyl, and 1.hexahydropyridyl, with 1-imidazolyl as should. The heterocyclic group having 1 to 4 atomic groups selected from oxygen, nitrogen, and sulfur atoms in the ring of R3 is a pyrrole ring in which A6 represents a single bond or R3 and A6 are bonded when a nitrogen atom is bonded to A6. The carbon atom on is a group bound as a carbon atom on the R3-C (= 0) -pyrrole ring. The substituent of R3 having 1 to 4 heterocyclic groups selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom in the substituted ring may be fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxyl group, or Substituted alkoxy, c 6 ~ C 1 G aryloxy, C 7 ~ C 9 aryloxy, C 2 ~ C 7 methoxy, keto, Cl ~ C6 Substitutable C2 ~ C7 alkyl groups, residues, C2 ~ C7 alkoxycarbonyl groups, carbamoyl groups, substitutable C2 ~ C7 alkylamine methylformamidine-81-(77) (77) 200526665 groups, amines Group, C ^ C: 6 alkylamino group which may be substituted, c2 ~ C7 alkylamino group which may be substituted, c2 ~ C 8 alkoxycarbonylamino group, C! ~ C 6 alkylsulfonamido group, cyano group, Nitro, C ^ C: 6 alkylthio, C! ~ C6 alkylsulfinyl, Cl ~ c6 alkylsulfinyl, amine sulfanyl, C 1 ~ C 6 amine sulfanyl, acid expansion Group, C3 ~ C6 alicyclic hydrocarbon group which may be substituted, Cl ~ c6 acyclic aliphatic hydrocarbon group which may be substituted, 4 aromatic hydrocarbon group which may be substituted, and heterocyclic group which may be substituted (having 1 in the ring) ~ 4 selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom) More substituents. The substituted ring of R3 has 1 to 4 heterocyclic groups selected from the heterocyclic group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the substituted ring. Specific examples are the same as those of the substituted C of the above G2] to C1G. Specific examples of the substituent of the cyclic aliphatic hydrocarbon group are the same as those shown. The substituted ring of R3 has an alkoxy group, a c2 to C7 fluorenyl group, a substituent group having 1 to 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, (2 to 2 〇7 alkylamine formyl, Ci ~ C6 alkylamine, c2 ~ c7 I, I3, c3 ~ c6 alicyclic hydrocarbon group, c1 ~ c6 acyclic aliphatic hydrocarbon group and C6 ~ M aromatic hydrocarbon group and Heterocyclic groups (with 1 to 4 atomic groups selected from the group consisting of oxygen, nitrogen, and sulfur atoms in the ring) can be further modified (fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, Ci ~ C6, such as ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, second butoxy, third butoxy, pentyloxy, and cyclopropoxy , Methoxymethyloxy '2 -methoxyethoxy, formamyl, ethenyl trifluoride, ethenyl, propionyl, butylamyl, isobutylamyl, pentamyl, and isopentamyl C2 ~ (: 7 ethyl group, keto group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropyl-82- (78) (78) 200526665 oxocarbonyl, butoxycarbonyl, isobutoxycarbonyl C3 ~ c7 alkoxy Carbonyl, carbamoyl, N-methylaminoformamyl, N, N-dimethylaminoformamyl, N-ethylaminoformamyl, N-ethyl-N-methylaminoformamyl , N, N-diethylamine formamyl, N-propylaminoformamyl, isopropylamine formamyl, N-butylamine formamyl, N-cyclopropylamine formamyl, And N_cyclopropylmethylaminomethyl, and other C2 ~ C7 alkylamine methylamido, amine, methylamino, ethylamino, propylamino, isopropylamino, dimethylamino, N_ethyl Alkylamino groups such as methylamino, diethylamino, N-methylpropylamino, N-methylisopropylamino, cyclopropylamino, and cyclopropylmethylamino '1-pyrrolidinyl, hexahydropyridyl , 4-methylhexahydropyridyl, N-hexahydropyridyl, and morpholinyl, and other rings having 1 to 2 rings selected from the group consisting of oxygen, nitrogen, and sulfur atoms Amine group, acetamido trifluoride, formamidine, acetamido, propylamino, butylamido, isobutylamido and pentamidine, etc. Cl ~ C7 amidoamine, methylamine Sulfonylamino, ethylsulfonamido, propylsulfonamido, and butylsulfonamido, etc. C] ~ C6 alkylsulfonamido, nitro, cyano, C6 ~ C6 alkyl, trifluoromethyl, and trifluoromethoxy One or more substituents selected by the group) are substituted. As an example of a substituent having i to 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the ring in which R3 may be substituted The preferred substituents are a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a cyano group, a nitro group, an amine group, a methylamine group, an ethylamine group, an propylamino group, an isopropylamine group, and a butylamine group which may be substituted. Group, isobutylamino group, second butylamino group, third butylamino group, pentylamino group, hexylamine group, dimethylamino group, N-ethylmethylamino group, diethylamine-83- (79) ( 79) 200526665, N-methylpropylamino, N-methylisopropylamino, N-methylbutylamino, N-methyl tertiarybutylamino, N-ethylisopropylamino, dipropylamino, CrCe—or dialkylamino, carboxyl, substituted methyl, ethyl, propyl, etc. formed by linear or branched alkyl and amine groups such as diisopropylamino and ethylbutylamino Isopropyl, butyl, isobutyl Saturated Ci-Q alkane such as second butyl, third butyl, pentyl, isopentyl, neopentyl, third pentyl, hexyl, isohexyl, 2-methylpentyl, and ethylbutyl C3 ~ C6 alicyclic hydrocarbon groups such as alkyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, substituted methoxy, ethoxy, propoxy, isopropoxy, butoxy , Isobutoxy, second butoxy, third butoxy, pentyloxy, isopentyloxy, neopentyloxy, third pentyloxy and hexyloxy And oxy groups (^ ~ 06 alkoxy groups, acetyl groups which can be substituted, propionyl groups, butyl fluorenyl groups, isobutyl fluorenyl groups, trimethylethyl fluorenyl groups, and hexamethylene groups, such as C2 to C7 fluorenyl groups, Thio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, second butylthio, third butylthio, pentylthio, and hexylthio, etc. C] ~ C6 Alkylthio, methyl trifluoride, trifluoromethoxy, triethylamine, propylamino, butylamino, isobutylamino, trimethylacetamido ' C2 ~ C7 amines such as hexamidine, and N-methylamine which can be substituted Formamyl, N-ethylaminoformamyl, N-propylaminoformamyl, N-isopropylamineformamyl, N-butylaminoformamyl, isobutylamineformamyl, Dibutylamine methylsalyl, N-pentylamine methylamyl, N, N-dimethylamine methylamyl, N-ethylmethylamine methylamyl, and N, N-diethylamine methyl C2 ~ C7 alkylamine formamidines formed by straight or branched alkyl groups such as fluorenyl groups and carbamoyl groups. The substituted ring of this R has four to four substituents selected from the group consisting of an oxygen atom 'nitrogen atom -84- (80) (80) 200526665 and a sulfur atom. A preferred example is a fluorine atom' chlorine atom. , Bromine atom, C2 ~ C4 fluorenyl group, hydroxyl group, carboxyl group, alkoxycarbonyl group, alkyl group which may be substituted, hydroxyl group, and alkoxy group which may be substituted. Methyl and ethyl are preferred. In the above formula (I), A6 is a group that binds R3 to a carbon atom of a pyrrole ring in the form of R3-CR3_8-CR3Q9 · pyrrole ring or C-pyrrole ring. R3 represents & In the case of a substituted C2 to C7 fluorenyl group, a carboxyl group, a C2 to C7 alkoxycarbonyl group, a carbamoyl group, a C2 to C7 alkylaminomethyl group which may be substituted, or a cyano group, the preferred examples are a methyl group, Ethyl, carboxyl, oxycarbonyl, ethoxyhydroxy, or cyano. The preferred combination of R3 and A6 in the above formula (1) is explained here. In the present invention, in the combination of R3 and A6 of the formula (I), when R3 is a fluorine atom, a chlorine atom, or an iodine atom, A3 represents a single bond. R3 is a trimethylsilyl group, a methylamino group, a C2 to C7 methyl group which may be substituted, a residue, a C2 to C7 alkyl group, a carbamoyl group, or a substituted C2 to C7 alkyl group. In the case of carbamoyl, or cyano, A6 is a carbon atom of the pyrrole ring that binds R3 and A6 in the form of R3-CR3G8 = CR3G9-pyrrole carbon atom or R3-C ^ C-pyrrole carbon atom. base. In the present invention, the preferred combination of R3 and A6 of the above formula (I) is that A6 shows a single bond 'R3 is a C6 ~ C! 4 aromatic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted. Among them, R3 is one or a plurality of (^ ~ (: ^ alkyl groups are preferably substituted. Epithienyl, pyridyl, furyl, pyrrolyl, pyrazolyl, or phenyl is wide and A6 is shown Single bond, R3 is Cl ~ C * alkyl or pyridyl or hydroxypyridyl, or pyrazolyl or methylazolyl substituted with one halogen atom -85- (81) 200526665. In addition, A6 is a single bond and R3 is a combination of a fluorine atom, a chlorine atom, bromogen ten, or virginium, A6 is a single bond, and R3 is a C that can be substituted. ~ ClG acyclic saturated fat A6 is a combination of a group of hydrocarbon groups, A6 is a single bond, and R3 is a combination of C3 ~ C8 alicyclic hydrocarbon groups that can be substituted, a6 is a single bond, and R3 is a combination of C6 ~ CM aromatic hydrocarbon groups that can be substituted, a Is a single bond, and R3 is a combination of a monocyclic C3 to C8 aromatic heterocyclic ring having 1 to 2 atomic groups selected from an oxygen atom, a nitrogen atom, and a sulfur atom in a ring which may be substituted, A6 ^ In order to make the carbon atom of the pyrrole ring bound to R3 and A6 be a group bonded in the form of the carbon atom of (= 0) -pyrrole ring, and R3 is a combination of hydrogen atoms, A6 is the carbon atom of the pyrrole ring bound to R3 and A6 R3-C (= 〇) -NH-pyridine ring carbon atom bonding group, and R3 is a group that can be substituted C] ~ C1G acyclic saturated aliphatic hydrocarbon group combination, A6 is the combination of R3 and A6 The pyrrole ring carbon atom is a group bonded in the form of R3-C (= 0) -NH-pyrrole ring carbon atom, and R3 is a combination of C3 ~ C8 alicyclic hydrocarbon group which can be substituted, and A6 is the combination of R3 and a6 ^ The carbon atom of the bonded pyrrole ring is a group bonded in the form of a carbon atom of r3-C (= 0) -NH-pyrrole ring, and R3 is a C6 ~ C! 4 aromatic hydrocarbon group combination that can be substituted. A6 is to make R3 The carbon atom of the pyrrole ring bonded to A6 is r3-c (= 〇) -NH-the carbon atom of the pyrrole ring forms a bonding group, and R3 is a ring that can be substituted and has 1 to 2 selected from oxygen atoms and nitrogen A6 is a combination of a monocyclic C3 ~ C5 aromatic heterocyclic group consisting of an atom and a sulfur atom. A6 is a pyrrole ring carbon atom in which R3 and A6 are bonded to each other in the form of R, NH · pyrrole ring carbon atoms. And R3 is a combination of hydrogen atoms. • 86- (82) (82) 200526665 A6 is a carbon atom in which R3 and A6 are bonded to the pyrrole ring as R, NH-pyrrole ring carbon atoms, and R3 Can be Instead of a combination of Cl ~ Cl () acyclic aliphatic hydrocarbon group, A6 is a group in which the carbon atom of the pyrrole ring that binds R3 and A6 is bonded as a carbon atom of the r, nh_pyrrole ring, and R3 is a group that can be substituted A combination of C3 to C8 alicyclic hydrocarbon groups, A6 is a group in which the carbon atom of the pyrrole ring that is bound to 113 and A6 is a carbon atom in the form of a pyrrole ring, and R3 is a combination of c6 to c14 aromatic hydrocarbon groups that can be substituted , A6 is the base that binds R3 and A6 to the carbon atom of the pyrrole ring as a carbon atom of R3-NH-pyrrole ring, and R3 has 1 to 4 in the ring which can be substituted! A monocyclic c3 to C 5 aromatic heterocyclic group selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, and A6 is a pyrrole ring carbon atom in which R3 and A6 are bonded as R3-HC = CH -A pyrido ring carbon atom bonded group, and R3 is a combination of hydrogen atoms, A6 is a pyrrole ring carbon atom bonding R3 and a6 is a group bonded in the form of R3-HC = CH-pyrillo ring carbon atom, and R3 is a combination of Cl ~ ClG non-cyclic saturated aliphatic hydrocarbon groups which can be substituted, A6 is a pyrrole ring carbon atom which binds R3 and A6 is a group which is bonded in the form of R3-HC = CH-pyrrole ring carbon atom, and R3 can be replaced by C3 ~ &lt;: A combination of 8 alicyclic hydrocarbon groups, A6 is a pyrrole ring carbon atom that binds R3 and A6 is a group bonded in the form of RlHC = CH-pyrrole carbon atom, and R3 is a C6 ~ C which can be substituted! The combination of 4 aromatic hydrocarbon groups, -87- (83) (83) 200526665 A6 is the D (t-ring carbon atom that binds R3 and A6). And R3 is a combination of monocyclic C3 ~ Cs aromatic aromatic heterocyclic groups which can have 1 to 2 atomic groups selected from oxygen, nitrogen, and sulfur atoms in the ring, and A6 is a combination of R3 and The carbon atom of the pyrrole ring bonded to A6 is a group bonded in the form of a carbon atom of the R3-C three C-pyrrole ring, and R3 is a combination of hydrogen atoms. The carbon atom of the pyrrole ring bonded to R3 and A6 is R3-Ce. C-pyrrole ring is bonded to the carbon atom form, and R3 is a combination that can be substituted (^ ~ (: 1 () acyclic saturated aliphatic hydrocarbon radicals, A6 is a pyrrole ring carbon that binds R3 and A6 The atom is a group bonded in the form of a carbon atom of R3-Ce C-pyrrole ring, and R3 is a combination of alicyclic hydrocarbon groups of C3 to C8 which can be substituted, and A6 is a pyrrole ring carbon atom in which R3 and A6 are bonded. C-pyrrole ring Carbon atom in the form of a bond, and R3 is a combination of C6 ~ C! 4 aromatic hydrocarbon groups that can be substituted, A6 is a pyrrole ring carbon atom that binds R3 and A6 is a carbon with R, C three C-pyrrole ring Atomically bonded groups, and R3 is a combination of monocyclic C3 ~ C5 aromatic heterocyclic groups having 1 or 2 atomic groups selected from oxygen, nitrogen, and sulfur atoms in the substituted ring , Or A6 is a combination of R3 and A5 in which the D-pyro ring fe atom is a group bonded in the form of a C-fluorenyl ring carbon atom, and R3 is a combination of a dimethylsilyl group or a cyano group. A description of the preferred combination of the r2_A5 part and the r3-A6 part in the formula (I). The combination of the part and the r and a6 parts, and A6 is a single bond is • 88- (84) (84) 200526665 R2 is acyclopropyl, cyclobutyl, cyclopropylmethyl, methyl, ethyl, ethyl, isopropyl, isobutyl, or 2-methyl-1-propanyl And R3 is more preferably a combination of pyridyl or b-hydroxypyridyl, or pyrazolyl or N-methylpyrazolyl substituted by a Ci ~ C4 alkyl or a halogen atom. Furthermore, both A5 and A6 Shows a single bond, R2 is be (^ ~ (^ The alkyl group, alkoxy group, C2 to C4 fluorenyl group, hydroxy group, carboxyl group, alkoxycarbonyl group, fluorine atom, or chlorine atom may be substituted by any one or a plurality of them, and may also represent thienyl, pyridyl, furyl, Pyrrolyl, pyrazolyl, or phenyl, and R3 is pyridyl or 1-hydroxypyridyl, or pyrazolyl or N-methylpyridyl substituted with a C! ~ C4 alkyl or a halogen atom The combination of the azole group is also good. In addition, the preferred combination of the A ^ G2 part, R2-A5 part and R3 · A6 part in the above formula (I) will be described. Basically, the combination of parts A ^ G2, R2-A5, and R3-A6 is better, and the best combination is also better. More specifically, among the combinations (a) to (f) listed below in the preferred combinations of A ^ G2, it is better to use A5 and A6 as single bonds. (a) A1 shows-(CH2) 2- or-(CH2) 3-, A2 shows -NH- (C = 0) or -NH- (C = 0) -NH-, G1 shows a single bond, A3 is Shown is a bivalent acyclic aliphatic hydrocarbon group. (b) A1 is--(CH2) 2-or (CH〗) 3 ·, A2 is -NH- (C = 0)-, -NH · (C = 0) · ΝΗ-, -NH ·, or -C (= 〇) -NH- and G1 are groups other than a single bond. (c) A1 is &lt; ^ ~ (: 6 divalent acyclic aliphatic hydrocarbon group, especially represents (CH2) or-(CH2) 3-, A2 represents a single bond, G1 is -89- (85) 200526665 heterocyclic ring which can be substituted (However, the $ 0 heterocyclic group is a single ring 0 # representing a 5 to 6-membered ring, the heterocyclic group of the 5 to 6-membered ring of G1 is substituted, or the A3-G2 moiety represents a hydrogen atom other than) d) A is Ci ~ c, valence acyclic aliphatic hydrocarbon group, especially-(ch2) 2 · or-(CH2) 3_, A2 is other than a single bond, it is an aromatic nicotyl group which may be substituted, may be Substituted c7 ~ c1 () alicyclic hydrocarbon groups, or heterocyclic groups that can be substituted (but when the aromatic hydrocarbon group of G1 is phenyl, or when the heterocyclic group of ^ is a single ring of five or six members, The phenyl group of G1 or a five- or six-membered monocyclic heterocyclic group is substituted, or the part of A3_G2 is other than a hydrogen atom.) (E) A1 is (^ ~ 〇: 6 divalent acyclic fat Group hydrocarbon groups, especially-(CH2) 2- or-(CH2) 3-, A2 is other than a single bond, G1 and A4 are single bonds, A3 is an irreplaceable Ci ~ Ci () acyclic fat Group hydrocarbon group, G2 is C5 ~ C1Q aliphatic hydrocarbon group which can be substituted, aromatic group which can be substituted (F) A1 represents a divalent acyclic aliphatic hydrocarbon group, especially-(CH2) 2-, or-(CH2) 3-, and A2 represents any other than a single bond, G1 shows a single bond, A3 shows an acyclic aliphatic hydrocarbon group which can be substituted, and A4 shows -C (= 0)-, -C (= 0) -NR121-, -C (= S) -NR122-,- C (= NR123)-, -0-C (= 0)-, -NR125-C (= 0)-, -NR126-S (0) 2-, -NR127-C (= 0) -0,- NR128-C (= 〇) -NR129-, -NR130- C (= S)-, -NR] 31-C (= S) -NR] 32-, -S-, -S (= 0)-,- S (= 0) 2-, -S (= 0) 2-NR133-, or-S (= 0) 2-0-. In the above (d) to (f), A2 is shown as-C (= 0) -, -C (= 0)--90 »(86) (86) 200526665 0 ·, -C (= 0) -NH-, -C (= 0) -NMe-, -NH-, -NH-C (20)-, -NH-C (= 0) -〇-, -NH-C (= 〇) -NH-, -NH-C (20) -NMe-, or -NH-C (= S )-Is especially indicated when-C (= 〇) -NH-, -nh,, -NH-C (= 0)-,-NH-C (= 〇)-〇-, or -NH · C (= 〇 ) NH- is appropriate. In each of these combinations, R2 is further shown as an acyclic aliphatic hydrocarbon group which may be substituted, a C3 ~ C8 alicyclic hydrocarbon group which may be substituted, a C6 ~ CM aromatic hydrocarbon group which may be substituted, or It is more preferred that the substituted heterocyclic group and R3 are a substituted aromatic hydrocarbon group or a substituted heterocyclic group. Further, in these cases, with 112 as (: 1 ~ € 1 () acyclic aliphatic hydrocarbon group, C3 ~ C8 alicyclic hydrocarbon group, phenyl group that can be substituted, or having 1 to 2 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, and R3 is a thienyl group, a pyridyl group, a furyl group, a pyrrolyl group, and a pyrazole group substituted with one or more alkyl groups A combination of phenyl groups or phenyl groups is preferred. In particular, R2 is acyclic propyl, methyl, ethyl, ethyl, isopropyl, isobutyl, or 2-methyl-]-propenyl, and R3 is When a Ci ~ C4 alkyl group or a halogen atom is substituted by a pyridyl or hydroxypyridyl group, or a Dtt pyridyl group or an N-methylpyrazolyl group, and R2 is an alkyl group, a Ci ~ cui endoxy group, or a chloro group Any or multiple substituted thienyl, pyridyl, pyranyl, pyrilyl, D [tn phenyl or phenyl, R2 is pyridyl substituted by a Ci ~ C4 alkyl group or a halogen atom or 1 · Hydroxypyridyl, or oxo, or N · methylpyrazolyl. The 'G1 -A 3 β A 4 -G2 moiety in the pyrrolopyrimidinone derivative represented by the above formula (I) A specific example of a preferable combination may be a base represented by the following chemical formula: K ^ Κ4 31 (87) 200526665. In the structure of each chemical formula, the symbol "... 一" means that A2 is combined with -G 1-A 3-A2-G2 CHj-+ ch3 CH3 ch3 K004 K005 .. ·· 〇--cf3 K010 K011 -¾ K015 F K016

--CH3 * 'Λ ch3 K001 K002 ch3 · &lt;-&lt; 3 K006 K007 -〇 -〇-F K012 K013' h3 K003 〇 -〇 K008 K009 • · θ K014

K017 K018 K019 K020 K021 K022 K023

92- (88) 200526665

〇h -〇- OCHs NH CH3

H2N

Vc% CH5 HN HN K042 K043 K044 K045 K046

H2N Cl HaN H3C-N

,. \ Jl Cl ch3

H2N F H2N H2 (SI H ^ N

K047 K04B

HZN CHa H2N

K049 H2N

K050 K051 H2N OCH3 H2N F K052 F K053

K054 Λ / Γ0Η3

H2N CFs

ch3 OCH3 K058 K059 K055 K056 K057

j) ’· Qj N &quot; H K065

-93 (89) 200526665

K077 K078 K079 K080 K081 h3c

H3C K087 K088 K082

K083 K084 K085 K0B8

K090 -0 -Os K091 K092 K089

K096

\ &gt; 〇H

F

K101 K102 K098 K099 K100 ^ y〇cH3 'K &quot; b K103 K104 K105 K106 -94- (90) 200526665

K107 K10B K109 -nP &quot; O --n [^-ch5 h3c ch3 K110 K111 K112

K143 K144 K145

-95- (91) 200526665

Ο Κ149 Κ150 Ο

cf3 Ο Κ151 Κ152 Κ153 --ί \ ~ F —N -och3 “· ν · Κ154 Κ155 Κ156 ΚΙ 57 OCH〇-Ν Ν ^ ΝΚ158 Κ159 Κ160 Κ161 —N Ν_ Γ. · Ν Ν ·

-〇 CH3 ί ~ \ dead ten CH3 ** Ν Ν— ^ CHs ^ Λ 162

Ο • Ν Ν—-λ--Ν Ν

Ο Ο Κ166 Κ167 Κ168 K169 K170 • Ν V-NH ch3-\-ch3 ch3 0. VCH3 —N V-NH —N V-NH ch3 Eight ch3 / -X Vn One -Ν V—NH (Κ171 Κ172 Κ173 Κ174 — Λ Ν) —ΝΗ / &gt; -Ν &gt; ~ ΝΗ 0 · Ο. • Ν: Κ175 Κ176 Κ177 Κ178 96- (92) 200526665 N ^ CH3 VN K179 • &lt; rcHs -q K180

Cl Κ1Θ1 K182

= \

CH, H3C C! K183 K1B4 Cl &lt; N

Cl F K186 C! K185 K1B7 K1B8 K189 K190

--H K191 K192 K193 K1S4 K195 K196 K197

--V h3c -ch3 K198 • b CH3 H3C CH3 K199 K200 CH3 -CH_ -v -¾ &quot; b K201 K202 K203 K204 〇-c -o ^! Ch3 Two ch3 K205 K206 K207 K208 K209 CH3 H3C K210 K211 &lt; ch3 ch3 ch3 fCH3 ch3 K212 K213 K214 K215 K216 K217 K218 ° -CH ^ H3C K219 K220 Λ yCHa, N-CH3 HN-^ (0 —1 K226Cl. CH3 -ch3

o-ch3 222 H3C b K223 h3c K227

Cl H3C K228 F,

H3C-O _λ-〇 Κ22Δ K225 CFa f3c

K230 K231 ch3 K232 ch3 One N CH3 K237 K233 K234 K235 K236 Factory CH3 N ^ CH3

K23B

… N K239 CH2 ch3 K240 K241 97- (93) 200526665 CH,

= CH K242 K243 〇-N K248 O CH3 K244 ../〇 K249 K250 ch3 '〇 &gt;-K245〇

S CH3 CH3 K246 F, Η

F

K247 F F

F F K251 K252 K253 CH3 K254 K255 K266 K259 &lt; CH3 CHa '-^ ch3 K260 K261 s ~ f ^ -CHa OH3 K257 K256 -Cxs: --〇 &lt; -〇3 K262 K263 K264 h3c, h3c Γ

OCH3 O K265 K266 OH / ~ v NH2 K267 K268 N-CH3 i. NH i K269 K270 -owing ~) &gt; = 〇 · _ai -owing &quot; &quot; &quot; ^ 〇chf2 ~ ^ ~ 〇cf3 • 隹 <~ K271 K272 K273 K274 K275 K276 CH3 ch3 ch3 _ch3 h3c ch3 K277 K278 K279 Κ2Θ0 K281 K2B2 b h3cn / ch3

.ch3 h3c ch3

CH3 K285 K283 K284 K286 K267 K288 -98 (94) 200526665 Κ289 o-ch3 ν 一 / ο- Κ290 Κ291 CHa 〇 ·· 〇 &lt; ΡΗο ~ VCHS CH3 Κ292 Κ293

-c ^: P &quot; S

O K294 K295 ch3 ch3 household ch3 h °

: Ί! Ch3 C3 ch3 ch3 K297 K293-· 〇 又 -〇 {CH3 h3c h3c ch3 ch3 c CH3 fCH3 CH3

K299 K300 K301 K302 K303 K304

K308

.. &lt; X

K308 n-ch3 'Ό K309 CH3 λ- * r' —CHa K310 K311 K312 K313-· \ N — \ VCH3 HjC CH3

-〇- \ -〇-y0CH3-〇- h3c —7 ch3 o ch3 ch3 h3c —7 ch3 och3

K314 K315 K316 K317 K318 K319 K320 K321 K322 K323 -99- (95) 200526665

K324 K325 K326 K327 K320 K329 K330 &quot; bCF3 1 · \ — o V cf3 ocf3 K331 K332 K333 K334 K335 K336-^ C) CH3 〇 谷 CH3 — ^ · ^ y ~ 〇CH3 och3 g &gt; ch3 h3c〇 / K338 K339 K340 K341 K342 K343 &quot; bCH3 \ — b ^ -3 A ch3 ch3 N-CHj h3c 'K344 K345 K346 K347 K348 K349

K350 K351 K352

K357 K358 K359 K360 NH2 NH2 HN-ch3 ^

K368

K365 K366. Cl K371 K372, cf3 K377 K378

K367

K373 K374

K379 K3B0 K381 Κ36δ K370

'Vcp3 &quot; VCFs f3c oh K582 K303 K364 -100 (96) 200526665 h3c -ch3 -ch3 h3c K385

H3C ^ hP K336 -CHa

I N h K387 K388 K369 ^ 〇Λί) CXCF3 K391 K392 CN K393 I ch3 K394 K390

CF3 CF3

K397 K395 K396 η3Λ ° νΗ3 h3XSH3 X »ch3 h3c och3

K401 h3c ch3 K407 CN

K402 H3C

K408 CH,

K414 K403 € H3 K409 V ^ 3 f3c och3 K413 K415

h3} ^ c3h3 H3c ch3 K398 K399 K400 'V〇H3 VCH3 * &gt; CH3 CH3 h3c 〇- \ 〇H3C NH 0 == ^ ch3 K404 K405 K406 • T T3 K410 K411 K412 CHS F -Female F ^ -ch3 F l 〇CH3 K416 K417 K41B

F

F h3c K419 -CH3 X-CH3 HnC CH3 K420 -ch3 o K421 KA22 K423 K424 K425 cf3 〇cf3

CF. K429 3 (/

OCFa K430 K426 K427 K428 K431 -101-(97) (97) 200526665 Among the pyrrolopyrimidinone derivatives represented by the above formula (I), a specific example of a preferable combination of -A5-R2 can be represented by the following chemical formula '166 Show base. The ‘symbol’ in each chemical formula indicates the binding site between the carbon atom of the ring and _ A5-R2. One -H… Cl… Br ——I-• ch3 one cf3 J001 J002 J003 J004 J005 J006 Λη3 ch3 ch3 ch3 —ten ch3 CHa '&quot; Vch3 ^ -ch3 _ · &lt;] HSC J007 J008 J009 J010 J011 J012 -ο -.Ο -〇-〇-〇H -O ^ oh J013 J014 J015 J016 J017 J018

J019 J020 J021 J022 J023 J024 HO OH H3CO 〇CH3 -〇-0H -〇-o-Tiller 3 J025 J025 J027 J028 J029 J030 Q-OH -o ^ OCHa 'ch3-• Office F -¾ J031 J032 J033 J034 J035 J036 H3C -Co h3c CH3-&lt; 3 Η3〇Λη3 A J037 J038 J039 J040 J041 J042 -102- (98) 200526665 h3c

J044 h3c

Cl \ V J045

H3C

J046 H3C h3c

0 J048 J047

/ == &lt; ch3 — J049 J050 J051 J052 J053 H-N: HHHH —N • -N-N… N 'ch3 ch3 ^ \ h3 &gt; ^ ch3 h3c J055 J056 J057 J058 J059 HHHHH —N' —rsf OCH3 One N —N —N ^ -CN 0) &gt; ta b J061 J062 J063 J064 J065 CH3 &quot; ΙΝΠohC J054 H -N CH3 CH3 J060 H — 〉〉 J066

J073 J074 CH2 ch3 -CHa J070 J071 CH3 -N ^ -CHg J076

… N CH3 ch2 J077 H3C J072 Factory CH3 One N ^ -CHs J078 -103- (99) 200526665 J079 ―Guang J086 JD93

r JOBO

CHS

H3C h3c ^ -ch3 H3VCH3 .. ^ CH2 J ch3 h3c -ch3 J0B1 JD82 J083 J084 J〇85 J〇87 J0B8 J089 J090 J091, CH3 CH3 -Si-CH3 ch3 CH〇 J092 0— J094 J095 J096 J097 J096 〇 och3

J099 XI J100 J101 J102 u ch3

CH, J106

Ns = \ &lt; T -〇 J103 J104 ch3 J105

J107 J10B 0) = N / = N (

CH3 / = N &quot; Oh J109 J110

Hac-o J111 J112 J113 CH3 J116 J117 CH3 Q-% &lt; J118 J119 J114 丨 a CH3 J115 OH NH2 0 J123 • 〇-CH3 PH J »J --CN J124 J125 J126; Ki HN \ J120 J121 J122

J127

-104- (100) 200526665

V h3c -CH3 h3c ch3 • ch3 -ch3 ch3 <ch3

• ch3 ch3 h3c J146 J147 J148 J149 J150 J151 J152 —b &quot; b -winter ch3 h3c ch3 F ^ C! Cl J153 J154 J155 J156 J157 J158 J159 Factory CH3

-N 'V ~ CH3

… O J160 J161 J162 J163 J164 J165 J166 Among the pyrrolopyrimidone derivatives represented by the above formula (I), a specific example of a preferable combination of the -a6-r3 moieties may be a group represented by the following chemical formula TOO bTl 81. In the structural formulae of each chemical formula, the symbol "..." indicates the binding site of the carbon atom of the pyrrole ring to -A6-R3. -105- 101200526665 T001 "CHa • -F but 002 -Ci T003 --f --Br T004 --I T005 --N〇2 T006 CF3 T007 CH3 Human CH3 -CHb CH3 T008 T009 T010 T011 CH3 but 012 T013 T014 .0 , 0 OCHb NH2 N-CH3 OH OChb T015 T016 T017 T018 h3c T019 T020 T021 -OCI ^ T022 T023 T024 OH k 0 Γ

^ N CH3 T025 T026 h3c T027 ΤΌ28 H2 — 'N-CHg… OH OCHb • CN 0 0 T029 Ding 030 T031 T032 T033 T034 T035 -V CH3 -V Λ Μ \ &quot; b Ding 036 T037 T038 T39 39 T040 T041 D042

Me CF3 T043 T044

OCHfe CN

F T045 T046 T047 T048 T049 -106- (102) 200526665 --OCH3 —SCHs -sP \ CHa CH Τ051 Τ052 T053 T054-· 〇Η Τ050 --NH • -M CHa --NH LCHs ch3 ch2 D057057 T058 T059- -ΝΗ2 "ΝΗ CH3 Τ055 Τ056

&quot; ^ X3 H --NH --NH fcH3 T070 T071 T072 T〇73 T074 T075 T076 --ΝΗ --ΝΗ --ΝΗ --ΝΗ 0 OH 0 OCHj 0 N-CHa h3c T077 T078 T079 T080

Τ081 Τ082 Τ083 -107- (103) 200526665 -NH Ο T084

1 NH 〇 T085

--NH NH &quot; NHcKi

--NH T086 ding 087 Τ0ΘΘ T0S9

-NH

-NH

-NH -NH / = \--NHK &gt; 0.

T094

—NH

T090 T091 Ding 092 • hVh 1ch3 ^ V〇h3 h3c Ding 096 T097 T098 T102 T103 T104 T093 T095 ch3 ch3 CHa o T099 T100 T101 f 1CN ·· T105 T106 T107 -CHa T106 T * J〇9 OH T110 T111 ch3

-CN T112 Λ 〇ch3 T113 h2n T114 ΊΓ115 F T116 T117 T118 • ch3 ch3 T119 120

Cl T121 T122 H2N ^ -CHs T122 <ch3 ch3 c ch3 ch3 CH3 4-ch3 T124 ding 125 T126 ch3 T127 ch3-=-Si-CH3 CH3 T128 -108- (104) 200526665 _〇-〇-cn Τ129 1Ί 30 Τ131 Τ132 Τ133 Τ134 Τ135 -_ύ OCF ^ Cl c -〇Λ —Γ \

och3 och3 CH3 T136 T137 D 138 T139 T140 ch3 V • Free -0 -ch3 / = N-^ /) -ο T142 T143 144 T145 D 146 N ch3 T141 -〇 T147 ch3

&quot; Ο -O &quot; O "O &quot;. 'T148 T149 T15D T151 D 152 T153 T154 CHa h3c-o

CN T155 T156 T157 T158 T159 T160 NC F F '0 T161 T162 T163 T164 T165 T166

H3C

0 0 H3C {_ · / ^ Η _ · / ^ Η \ ^ N \ ^ N \ ^ N CH3 ch3 T167 T168 T169 Ding 170 T171 T172 T173 '◊ΝΗ ^ T174 T175 T176 T177 T17B T179 T180 T181

A specific example of the pyrrolopyrimidinone derivative represented by the above formula (I) is A1 as a compound having the group shown in Table 1 below, and A2 as a compound having the group shown in Table 1 below as _G ] -A3-A4-G2 is a compound having the group represented by the above formula K001-K431, as -A5-R2 is a compound having the group represented by the above formula J0 :: 66 Compounds of the group shown by -109- (105) 200526665 TOO 1-T181, and any combination thereof. Among them, preferred specific examples are the compounds described in Table 1. Table 1 Compound numbersA1--A2- -G, A3-A4-G2 -A £ .R2 -a6-r3 1-(ch2) 2- -c (= o)-K002 J001 T148 2-(ch2) 2 -C (= 0) K002 J001 T151 3-(CH2) 2- -C (= 0)-K003 J001 T148 4 _ (CH2h · -C (= 0)-K003 J001 T151 5-(CH2) 2- -c (= o)-K004 J001 T148 6-(ch2> 2- • C (= 0)-K004 JD01 T151 7-(CH2) 2- -C (= 0). K005 J001 T148 8-(CH2) 2 --c (= o)-K005 J001 T151 9-(CH2) r -C (= 0)-K007 J001 T148 10-(CH2) 2- -c (= o)-K007 J001 Ding 152 11-(CH2) 2- -C (= 0)-K008 J001 T148 12-(CH2) 2- -C (= 0)-K008 J001 T152 13-(ch2) 2- -C (= 0)-K009 J001 T148 14-(CH2 ) 2- -C (= 0)-K009 J001 T152 15-(CH2) r -C (= 0)-K012 J001 T148 16 • (CH2) 2 · -c (= o) · K012 J001 T152 -1 * 7 -(CH2) 2- -C (sO)-K107 J0Q1 T14S 18-(CH2) 2- -C (= 0)-K107 J001 T168 19-(ch2) 2- • c (= o)-K108 J001 T148 20 -(CH2) 2. -C (= o)-K108 J001 T169 21-(CH2) 2 · -C (= 0)-K112 J001 T148 22-(CH2) 2- • c (= o)-K112 J001 T170 23-(ch2) 2 · -C (= 0). K129 J001 T148 24-(CH2) 2- -C (= 0)-K129 J001 T171 25 • (ch2) 2 · -c (= o)-K133 J001 T148

-110- 200526665 (106) Compound number -A1 · -A2- -g1-a3-a4-g2 -A, R2 -A, R3 26 • (CH2) 2- -C (= 0)-K133 J001 T172 27- (CH2) 2. -C (= o)-K137 J001 T148 28-(CH2) 2- -C (-0)-K137 J001 T173 29-(CH2) 2- -C (= 0) -NH- K007 J001 T148 30-(CH2) 2- -C (= 0) -NH- K012 J001 T148 31-(CH2) 2- -0 (= 0) -0 · K001 J001 T148 32 • (CH2) 2. -C (= 0) -0- K002 J001 T151 33-(CH2) 2 · -C (= 0) -0- K193 J001 T152 34 • (ch2> 2- ~ 0 (= O) -O- K227 J001 T169 35-(CH2 ) 2- -C (= 0) -0- K002 J001 T148 36-(CH2) 2- -NH- K181 J012 T148 37-(CH2) 2- -NH- K181 J012 T151 38-(CH2) 2_ -NH- K181 J012 T152 39-(CH2) 2- -NH- K181 J012 T169 40-(ch2) 2 · -NH- K181 J045 T148 41 ， (CH2) 2 · -NH- K181 J045 T151 42-(CH2) 2 ·-- NH · K181 J045 T152 43-(CH2) 2- • NH- K181 J045 T169 44-(ch2) 2. -NH · K181 J045 T170 45-(CH2) 2, • NH- K181 J045 T172 46-(CH2) 2 -• NH- K182 J012 Ding 148 47-(CH2) 2 · -NH- K182 J012 T151 48-(ch2) 2. -NH- K182 J012 T152 49-(ch2) 2 · -NH · K182 J012 T169 50-( CH2) 2- -NH- K182 J045 T148 -111-200526665 ( 107) Compound No.-A1- -A2- -G1-A3-A4.G2 -a5-r2 -Ae_R3 51, (CH2) r -NH- K182 J045 T151 52-(CH2) 2- -NH- K182 J045 T152 53 -(CH2) 2- -NH- K182 J045 T169 54-(ch2) 2- -NH- K182 J045 T170 55 _ (ch2) 2 '-NH- K182 J045 T172 56-(CH2) 2- • NH- K183 J012 T148 57-(CH2) 2 · • NH · K183 J012 T151 58-(CH2) 2. -NH- K183 J012 T152 59-(CH2) 2. • NH- K183 J012 T169 60-(CH2) 2- -NH · K183 J045 T148 61-(CH2) 2- -NH- K183 J045 T151 62-(CH2) 2 · -NH- K183 J045 T152 63-(CH2) 2- -NH- K183 J045 T169 64-(CH2) 2- • NHK183 J045 T170 65-(CH2) 2- • NH- K183 J045 T172 66-(CH2) 2- -NH- K184 J012 T148 67-(CH2) 2. -NHK184 J012 T151 68-(CH2) 2 --NH- K184 J012 T152 69-(ch2) 2 · -NH- K184 J012 T169 70 _ (ch2) 2- • NH- K184 J045 T148 71-(ch2) 2- • NH- K184 J045 T151 72 • (CH2 ) 2- -NH- K184 J045 T152 73 _ (CH2) r -NHK184 J045 T169 74 • (ch2) 2 · -NH- K184 J045 T170 75-(CH2) 2- • NH- K184 J045 T172 -112- 200526665 (108) Compound No.-A1- -A2. • G, A3-A4-G2 -As-R2 • Ae-R3 76-(ch 2) 2- • NH- K185 J012 T148 77 • (CH Shi, -NH- K185 J012 T151 78 _ (CH2) r -NH- K185 J012 T152 79-(CH2) 2 · -NH- K185 J012 Ding 169 80- NH- K185 J045 T004 81-(CH2) 2- -NH- K185 J045 T005 82-(CH2) 2- -NH- K185 J045 T090 83-(CH2) 2- • NH- K185 J045 T129 84-(CH2) 2 ^ -NH- K185 J045 T148 85 • (ch2) 2 · -NH · K185 J045 T151 86-(CH2) 2- -NH- K185 J045 T152 87 _ (ch2) 2- • NH- K185 J04S T169 88-(CH2 ) 2 · NH- K185 J045 T170 89-(ch2) 2- -NH- K185 J045 T172 90 _ (CH2) 2_ -NH- K186 J012 T148 91-(ch2) 2 · • NH- K186 J012 T151 92-( CH2) 2- -NH · K186 J012 T152 93-(CH2) 2- • NH- K186 J012 T169 94-(ch2) 2. -NH- K186 J045 T148 95-(CH2) 2- -NH · K186 J045 T151 96 _ (CH2) 2 · • NH · K186 J045 T152 97 '(CH2) 2_ -NH- K186 J045 T169 Θ8-(CH2) 2- -NH- K186 J045 T170 99-(ch2) 2 · -NH- K186 J045 T172 100-(CH2) 2 · -NH- K187 J012 T148 -113- (109) Compound number -A1- • A2 · -g, a3-a4-g2 -A, R2 • A, R3 101-(CH2) 2, -NH- K187 J012 T151 102-(CH2) 2- -NH- K187 J012 T152 103-(CH2) r -NH- K187 J012 T169 104-(CH2) 2 · -NH- K187 J045 T148 105 • (CH2〉 2- -NH- K187 J045 T151 106-(ch2) 2- -NH- K187 J045 T152 107-(CH2 ) 2- -NH- K187 J045 T169 108 • (ch2) 2 · -NH · K187 J045 T170 109-(CH2) 2_ -NH- K187 J045 T172 110-(CH2) 2- • NH- K188 J012 T148 111-( ch2) 2 · -NH- K188 J012 T151 112-(CH2) 2- • NH- K188 J012 T152 113 • (ch2〉 2 · -NH- K188 J012 T169 114-(CH2) 2- • NH- K188 J045 T148 115 -(ch2) 2- -NH- Κ18Θ J045 T151 116 • (ch2) 2 · -NH- K188 J045 T152 117-(CH2) 2- -NH- K188 J045 Ding 169 118-(CH2) 2- -NH- K188 J045 T170 119-(CH2) 2- • NH- K188 J045 T172 120 _ (CH Shi · -NH- K189 J012 T148 121-(CH2) 2- -NH- K189 J012 T151 122-(ch2) 2--NH- K189 J012 T152 123 • (CH2) 2- -NH- K189 J012 T169 124-(CH2) 2 · -NH- K189 J045 T148 125 • (ch2) 2- • NH- K189 J045 T151 -114- 200526665 (110) -A, -A2- -g, a3-a4-g2 -a5-r2 -A, R3 126-(CH2) 2_ -NH- K189 J045 T152 127-(ch2) 2- -NH- K189 J045 169 128-(CH2) 2- -NH- K189 J045 T170 129-(CH2 ) 2_ -NH- K189 J045 T172 130-(ch2) 2- -NH- K190 J012 T148 131-(CH2) 2- -NH- K190 J012 T151 132-(CH2) 2 · -NH- K190 J012 T152 133 • ( CH2) 2- -NH- K190 J012 T169 134-(CH2) 2- -NH- K190 J045 T148 135-(CH2) 2- -NHK190 J045 T151 136-(CH2) 2- -NHK190 J045 T152 137 • (CH2) 2. • NH- K190 J045 T169 138-(CH2) r -NH · K190 J045 T170 139-(CH2) 2- • NH · K190 J045 T172 140-(ch2) 2- -NH- K191 J012 T148 141-(CH2) 2- • NH- K191 J012 T151 142 • (ch2) 2- -NH- K191 J012 T152 143-(CH2) 2--NH- K191 J012 T169 144-(CH2) 2- -NH · K191 J045 T148 145 • (CH2) 2- -NH- K191 J045 T151 146-(CH2) 2, -NH · K191 J045 T152 147-(CH2) 2- -NH- K191 J045 T169 148-(CH2) r -NH- K191 J045 T170 149-(ch2) 2- -NH- K191 J045 T172 150-(CH2) 2 ·· NH · K192 J012 T148 -115- 200526665 (111) Compound No.-A1- • A2- -a5-r2 -a6 -r3 151-(ch2) 2- -NH · K192 J012 T151 152-(ch2) 2 · -NH- K192 J012 T152 153-(CH2) 2- -NH- K192 J012 T169 154-(CH2) 2- -NH -K192 J045 T148 155-(CH2) 2- -NHK192 J045 T15 1 156 • (CH2) 2- -NH- K192 J045 T152 157 • NH · K192 J045 T169 158 • (ch2) 2- -NH · K192 J045 T170 159-(CH2) 2 · • NH- K192 J045 T172 160 • ( CH2) 2- -NH- K193 J012 T148 161-(CH2) 2 · -NH- K193 J012 T151 162 • (ch2) 2- -NH- K193 J012 T152 163 -_2 · • NH · K193 J012 T169 164-(CH2 ) 2. -NH- K193 J045 T148 165-(CH2) 2_ -NH- K193 J045 T151 166-(CH2) r -NHK193 J045 T152 167 、 (ch2) 2 · NHNH K193 J04S T169 168-(ch2 ) 2--NH · K193 J045 T170 169 • (CH2) 2- -NH- K193 J045 T172 170-(CH2) 2- -NH- K194 J012 T148 171 • (CH2) 2- -NH- K194 J012 T151 172 _ (CH2) 2- -NH- K194 J012 Ding 152 173-(CH2) 2 · • NH · K194 J012 T169 .174-(ch2) 2. • NH- KH94 J045 T148 175-(CH2) 2- • NH- K194 J045 T151 -116 200526665 (112) Compound number -A1- -A2- -G, A3-Aa-G2 -A, R2 • A, R3 176-(CH2) 2 ~ -NH- K194 J045 T152 177 • (ch2) 2- -NH- K194 J045 T169 178-(CH2) 2. -NH- K194 J045 T170 179 •-(ch2) 2 · -NH · K194 J045 T172 180-(CH2) 2_ • NH- K195 J012 T148 181-( CH2) 2. -NH- K195 J01 2 T151 182-(CH2) 2- -NH- K195 J012 T152 183-(CH2) r -NH- K195 J012 T169 184-(CH2) 2- -NH · K195 J045 T148 185-(CH2) 2, • NH- K195 J045 T151 186-(CH2) 2- -NH- K195 J045 Ding 152 187-(CH2) 2 · -NH- K195 J045 T169 188 • (ch2) 2- -NH- K195 J045 T170 189-(ch2) 2_- NH- K195 J045 T172 190-(ch2) 2. -NHK196 J012 T148 191-(CH2) 2_ -NH- K196 J012 T151 192-(CH2) 2- -NH- K196 J012 T152 193-(CH2) 2- -NH- K196 J012 T169 194-(CH2) 2- -NH- K196 J045 T148 195-(ch2) 2- -NH- K196 J045 T151 196-(CH2) 2- -NHK196 J045 T152 197 • (ch2) 2 · -NH · K196 J045 T169 198-(CH2) 2- • NH- K196 J045 T170 199-(CH2) 2- • NH- K196 J045 T172 200, (CH2) 2- -NH- K197 J012 T148 -117- 200526665 (113) Compound number-A1- • A2 · -g, a3-a4-g2 -A, R2 -A6-R3 201-(CH2) 2- -NH- K197 J012 T151 202-(ch2) 2- -NH -K197 J012 T152 203-(CH2) 2- -NH- K197 J012 T169 204-(CH2): r. -NH · K197 J045 T003 205-(ch2) 2- -NH- K197 J045 T004 206-(CH2) r -NH- K197 J045 T005 207 &quot; (CH2) 2 · NH- K197 J045 T077 208-(ch2) 2. -NH- K197 J045 T090 209-(CH2) 2- -NH- K197 J045 T148 210-(CH2) 2- -NH- K197 J045 T151 211-(CH2) 2. -NH · K197 J045 T152 212-(ch2) 2- -NH- K197 J045 T161 213-(CH2) 2- -NH- K197 J045 T169 214 • (ch2) 2- -NH- K197 J045 T170 215-(CH2) 2- • NH, K197 J045 T172 216-(ch2) 2. -NH-C (= 0)-K001 J001 T129 217 • (CH2) 2- -NH-C (= 0)-K001 J045 T148 218-(ch2) 2- • NH-C (= 0) K002 J002 T130 219 • (CH2) 2- -NH-C (= 0)-K002 J045 T148 220-(CH2) 2- -NH-C (= 0) ^ K003 J001 T148 221 • (ch2) 2- -NH-C (= 0). K003 J001 T169 222-(CH2) 2- • C (= 0) K003 J008 T134 223-(CH2) 2- -NH-C (= 0) -K003 J008 T148 224-(CH2) r -NH-C (= 0) K003 J009 T148 225-(CH2) 2- -NH-C (= 0)-K003 J012 T148 118- (114) Compound number A1- -A2- -g, a3-a4-g2 -A, R2 -A6.R3 226-(CH2) 2. • NH-C (= 0〉-K003 J018 T148 227-(CH2) 2 · -NH-C ( = 0)-K003 J018 T152 228-(CH2) 2- -NH-C (= 0)-K003 J035 T148 229-(CH2) 2- -NH-C (= 0)-K003 J035 T151 230-(CH2) r · -NH-C (= 0)-K003 J045 T148 231-(CH2) 2- -NH-C (= 0)-K003 J052 T148 232-(CH2) 2- -NH-C (= 0)-K003 J052 T169 233-(CH2) 2- -NH-C (= 0)-K003 J069 T148 234 (CH2) 2- -NH-C ( = 0)-K003 J069 T152 235-(CH2> 2- -NH-C (= 0)-K004 J003 T148 236-(ch2) 2 · -NH-C (= 0) · K004 J003 T152 237-(CH2) 2- -NH-C (= 0)-K004 J008 T148 238-(CH2) 2. -NH-C (= 0)-K004 J009 T135 239-(CH2) 2- -NH-C (= 0)-K004 J009 T148 240-(CH2) r -NH-C (= 0)-K004 J012 T148 241-(CH2) 2- -NH-C (= 0)-K004 J020 T148 242-(ch2) 2- -NH-C (= 0). K004 J020 T151 243-(CH2) 2- -NH-C (= 0)-K004 J037 T148 244-(CH2) 2- -NH-C (= 0)-K004 J037 T169 245-(ch2 ) 2- -NH-C (= 0)-K004 J045 T148 246-(ch2) 2- -NH-C (= 0)-K004 J054 T148 247 • (ch2) 2. -NH-C (= 0) · K004 J054 T152 248-(CH2) 2- -NH-C (= 0)-K004 J071 T148 249 • (CH2) 2 · -NH-C (= 0). K004 J071 T151 250-(CH2) 2- -NH -C (= 0)-K005 J008 T148 • 119- (115) Compound number -A1 · -A2- -g, a3-a4-g2 • A5.R2 • A, R3 251-(CH2) 2 · • NH- C (= 0)-K005 J009 T148 252-(CH2) 2- -NH-C (= 0)-K005 J012 Ding 145 253-(CH2) 2 · -NH-C (= 0). K005 J012 Ding 148 254 -(CH2) r -NH ~ C (= 0) -K005 J045 T148 255-(CH2) 2- -NH-C (= 0) K006 J008 T148 256-(CH2) 2_ -NH-C (= 0)-K006 J009 T148 257-(CH2) r -NH- C (= 0). K006 J012 T148 258-(CH2) 2 · -NH-C (= 0)-K006 J014 T148 259-(ch2) 2- -NH-C (= 0). K007 J004 T148 260-( ch2) 2- -NH-C (= 0). K007 J004 T169 261-(CH2) 2_ _NH-C (= 0)-K007 J008 T148 262 _ (CH2); t -NH ~ C (= 0)-K007 J009 T148 263-(CH2) 2 · -NH-C (= 0)-K007 J012 T148 264-(CH2) z- -NH-C (= 0) · K007 J015 T149 265-(QH2) 2, -NH- C (= 0)-K007 J021 T148 266-(CH2) 2- -NH-C (= 0). K007 J021 T152 267 • (ch2) 2- • NH-C (O)-K007 J038 T148 268-(ch2 ) 2- -NH-C (= 0)-K007 J038 T151 269-(CH2) 2- -NH-C (= 0)-K007 J045 T148 270-(CH2) 2- -NH-C (= 0). K007 J055 T148 271-(ch2) 2. -NH-C (= 0)-K007 J055 T169 272-(CH2) 2_ -NH-C (= 0)-K007 J072 T148 273-(CH2) r -NH-C (= 0)-K007 J072 T152 274-(CH2) 2- -NH-C (= 0)-K008 J005 T148 275-(CH2) 2- -NH-C (= 0). K008 J005 T151 -120- ( 116) Compound No.A1- • A2- -G, A3-A4-G2 -As-R2 -As-R3 276-(CH2) 2_ -NH-C (= 0)-K008 J008 T148 277-(ch2) 2 --NH-C (= 0) -K008 J008 T152 278-(CH2) 2--NH-C (= 0)-K008 J009 T148 279-(CH2) 2- • NH-C (= 0)-K008 J009 T152 280-(CH2) 2-- NH-C (= 0)-K008 J012 T148 281-(CH2) 2_ -NH_C (= 0) _ K008 J012 T152 282 _ (CH2) r -NH-C (= 0)-K008 J018 T151 283-(ch2) 2 · -NH-C (= 0)-K008 J022 T148 284-(ch2) 2. -NH-C (= 0)-K008 J022 T169 285-(ch2) 2- -NH-C (= 0) · K008 J039 T148 * 286 • (CH2) 2- -NH-C (= d)-K008 J039 T152 287 • (CH2) 2- -NH-C (= 0)-K008 J045 T148 288-(CH2) 2- -NH -C (= 0) K008 J045 T152 289 _ (CH2) 2 · -NH-C (= 0)-K008 J056 T148 290-(CH2) 2_ -NH-C (= 0)-K008 .J056 T151 291- (CH2) 2 · -NH-C (= 0) · K008 J073 T148 292 • NH-C (= 0)-K008 J073 T169 293 _ (ch2) 2- -NH-C (= 0). K009 J006 T148 294 -(CH2) 2- -NH-C (= 0)-K009 J006 T152 295-(ch2) 2 · -NH-C (= 0)-K009 J008 T148 296-(ch2) 2. -NH-C (= 0)-K009 J009 T148 297-(ch2) 2--NH-C (= 0). K009 J012 T148 298-(ch2) 2, -NH-C (= 0 &gt; K009 J023 T148 299-(CH2) 2- -NH-C (= 0). K009 J023 T151 300-(CH2) 2 · -NH-C (= 0). K009 J040 T148 -121 · (117) 200526665 Compound No.-A1- -a2 _ -g1-a3-a4-g2 -As-R2 -Ae-R3 301-(ch2) 2- -NH-C (= 0)-K009 J040 T169 302 • (ch2) 2_ -NH-C (= 0) -K009 J043 Ding 152 303-(CH2) 2 · -NH-C (= 0)-K009 J045 T148 304-(CH2) r -NH-C (= 0) K009 J057 Ding148 305-(ch2) 2_ • NH-C (= 0)-K009 J057 T152 306 • (ch2) 2- -NH-C (= 0). K009 J074 T148 307-(〇h2) 2- -NH-C (= 0)-K009 J074 D 151 308-(CH2) 2 · • C (= 0)-K010 J045 T157 309-(CH2) 2- -NH-C (=. ) K011 J007 T148 310 _ (CH2) r -NH-C (= 0)-K011 J007 T169 311-(ch2) 2_ -NH-C (= 0)-K011 J008 T148 312 * (CH2) 2- -NH -C (= 0)-K011 J009 T148 313-(CH2) 2- -NH-C (= 0)-K011 J012 T148 314-(ch2) 2- -NH-C (= 0)-K011 J024 T148 315- (CH2) r -NH-C (= 0). K011 J024 T152 316 • (CH2) 2- -NH-C (= 0)-K011 J041 T148 317-(CH2) 2. -NH-C (= 0) -K011 J041 T151 318-(CH2) 2- -NH-C (= 0)-K011 J045 T003 319-(CH2) 2- -NH-C (= 0). K011 J045 T004 320-(CH2) 2- -NH-C (= 0)-K011 J045 T005 _ 321-(CH2) 2- -NH-C (= 0)-K011 J045 T148 322-(CH2) 2 · NH-C (= 0 K011 J058 T148 323-(CH2) 2 · -NH-C (= 0)-K011 J058 T169 324-(CH2) 2- -NH-C (= 0)-K011 J063 T158 325-(CH2) 2 · -NH-C ( = 0) K011 J075 T148 -122- (118) Compound number_A1 • A2- -g1-a3-a4-g2 -a5-r2 -a6-r3 326-(CH2) 2 * -NH-C (= 0)-K011 J075 T152 327-(CH2) 2- -NH-C (= 0)-K012 J008 T148 328-(CH2) 2- -NH-C (= 0)-K012 J008 T151 329-(ch2) 2 -• MH-C (= 0)-K012 J009 T148 330-(CH2) 2- .NH-C (= 0)-K012 J012 T148 331-(CH2) 2 · -NH-C (= 0)-K012 J025 T148 332-(ch2) 2- -N HC (= 0)-K012 J025 T169 333-(CH2) 2 · -NH-C (= 0) · K012 J042 T148 334-(CH2) 2- -NH-C (= 0)-K012 J042 T152 335-( CH2) 2- -NH-C (= 0)-K012 J045 T148 336-(ch2) 2. -NH-C (= 0)-K012 J059 T148 337 • (CH2) 2- -NH-C (= 0) -K012 J059 T151 338 • (CH2) 2_ -NH-C (= 0)-K012 J076 T148 339-(ch2) 2 · -NH-C (= 0) · K012 J076 T169 340-(CH2) 2- -NH -C (= 0)-K012 J081 T164 341-(CH2) r -NH-C (= 0)-K013 J001 Ding 168 342-(CH2) 2- -NH-C (= 0)-K013 J008 T148 343- (CH2) 2. -NH-C (= 0)-K013 J012 T148 344-(CH2) 2- -NH-C (= 0)-K013 J045 T005 345-&lt; ch2) 2_ -NH-C (= 0 )-K013 J045 Ding 077 346-(CH2) 2- -NH-C (= 0)-K013 J045 Ding 090 347 • (ch2) 2- -NH-C (= 0)-K013 J045 T129 348 • (ch2) 2- -NH-C (= 0)-K013 J045 T148 349-(CH2) 2- -NH-C (= 0). K014 J002 T169 350-(CH2) r -NH-C (= 0) K015 J008 T170 -123- 200526665 (119) Compound number -A, • A2- -G, A3-A4_G2 -a5-r2 -AS'R3 351-(ch2) 2- -NH-C (= 0)-K016 J009 T173 352 • (CH2) 2_ -NH-C (= 0)-K017 J012 T176 .353-(CH2) 2- -NH-C (= 0)-K018 J014 T178 354-(ch2) 2- -NH-C (= 0)-K019 J015 T129 355-(ch2) 2- -NH-C (= 0)-K020 J018 T130 356-(CH2) 2_ -NH-C (= 0)-K021 J043 T134 357-(CH2) 2 · -NH-C (= 0)-K022 J045 T135 358-(cm -NH-C (= 0)-K023 J063 T145 359-(ch2) 2_ -NH-C (= 0)-K024 J081 T148 360-(CH2) 2 ·-- NH-C (= 0)-K025 J001 T149 361-(ch2) 2. K025 J045 T148 362-(CH2): r -NH-C (= 0)-K026 J002 Ding 151 363-(CH2) 2- -NH -C (= 0)-K027 J008 T152 364-(ch2) 2- -NH-C (= 0)-K028 J009 T157 365 • (ch2) 2- -NH-C (= 0)-K029 J012 T158 366- (CH2) 2. -NH-C (= 0)-K030 J014 T164 367 * (CH2) 2 · -NH-C (= 0)-K031 J015 T168 368-(CH2) 2- -NH ~ C (= 0 )-K032 J018 T169 369-(ch2) 2- -NH-C (= 0)-K033 J043 T170 370-(CH2) 2- -NH-C (= 0)-K033 J045 T004 371-(ch2) 2. • NH-C (= 0〉 K034 J045 T173 372-(CH2) 2- -NH-C (= 0)-K035 J063 T176 373 • (CH2) r -NH-C (= 0) K036 J081 T178 374 • (ch2) 2- -NH-C (= 0)-K037 J001 Ding 129 375-(CH2): r .NH-C (= 0). K038 J002 T130

124 (120) Compound No.-A1- -A2 · G, A3-A Gas G2 • As-R2 -a6-r3 376-(ch2) 2- -NH-C (= 0)-K039 J008 T134 377-( ch2) 2 · -NH-C (= 0)-K040 J009 T135 378 ， (CH2) 2- -NH-C (= 0)-K041 J012 T145 379-(CH2) 2- -NH-C (= 0) -K042 J014 T148 380-(ch2) 2 · -NH-C (= 0) · K043 J015 T149 381-(CH2) 2- • NH-C〇 = 0)-K044 J010 T148 382-(CH2) 2-. NH-C (= 0). K044 J010 T169 383-(ch2) 2. • NH-C (= 0)-K044 J018 T151 384-(CH2) 2- -NH-C (= 0)-K044 J027 T148 385 -(CH2) 2- • NH-C (= 0)-K044 JD27 T152 386 • (CH2) 2. -NH-C (= 0)-K044 J044 T148 387-(CH2) 2- -NH-C (= 0)-K044 J044 T151 388 • (CH2) 2 · -NH-C (= 0)-K044 J061 T148 389-(CH2) 2- -NH-C (= 0)-K044 J061 T169 390-(CH2) 2 --NH-C (= 0) K044 J078 T148 391-(ch2) 2- -NH-C (= 0) ^ K044 J078 T152 392-(CH2) 2, _NH-C (= 0)-K045 J043 T152 393-(CH2) 2- 'NH-C (= 0)-K046 J045 T157 394-(CH2) 2 · -NH-C (= 0)-K047 J063 T158 395 • (CH2) 2_ • NH-C (O )-K048 J081 T164 396-(CH2) 2. -NH-C (= 0)-K049 J001 T168 397-(CH2) 2- -NH-C (= 0). K050 J002 T169 398-(CH2) 2- -NH-C (= 0)-K051 J008 T170 399 • (CH2) 2- -NH-C (= 0). K052 J009 T173 400 _ (ch2) 2- -NH-C (= 0)-K053 J012 T176 -125- (121) Compound number-A1- -A2- -g1-a3-a4-g2 -a5-r2 -a6_r3 401-(CH2> 2 · -NH-C (= 0) «K054 J014 T178 402-(CH2) 2- -NH -C (= 0)-K055 J015 T129 403-(ch2) 2. -NH-C (= 0) K056 J018 T130 404 • (ch2) 2- -NH-C (= 0)-K057 J043 T134 405- (ch2) 2- -NH-C (= 0)-K058 J045 T135 406-(CH2) 2- -NH_C (= 0)-K059 J063 T145 407 &gt; (CH2) 2- -NH-C (= 0) -K060 J081 T148 408-(CH2) 2- -NH-C (= 0)-K061 J001 T149 409-(ch2) 2- -NH-C (= 0)-K062 J002 T151 410,-(CH2) 2- -NH-C (= 0)-K063 J008 T152 411-(CH2) r * -NH-C (= 0)-K064 J009 T157 412 • (CH2) r -NH-C (= 0)-K065 J012 T158 413 -(CH2) 2- -NH-C (= 0)-K066 J014 T164 414-(CH2) r -NH-C (= 0)-K067 J015 T168 415-(CH2) 2- -NH-C (= 0 ) «K068 J018 Ding 169 416-(CH2) 2- &gt; NH-C (= 0)-K069 J043 T170 417-(CH2) 2. -NH-C (= 0)-K070 J011 T148 418-(CH2) 2--NH-C (= 0)-K070 J011 T151 419-(CH2) 2- -NH-C (= 0)-K070 J028 T148 420-(ch2) 2- -NH-C (= 0)-K070 J028 T169 421-(ch2) 2_- NH.C (= 0), K070 J045 T148 422 • (ch2) 2- -NH-C (= 0) K070 J045 T152 423 • (CH2) 2- -NH-C (= 0) K070. J045 T173 424-(CH2) 2 · -NH-C (= 0)-K070 J062 T148 425-(ch2) 2- -NH-C (= 0)-K070. J062 T151 -126- (122) Compound number A1-- A2- -g1-a3-a4-g2 • a5-r2 -A $ -R3 426-(CH2) r -NH-C (= 0)-K070 J079 T148 427-(CH2) 2- -NH-C (= 0) · K070 J079 T169 428-(CH2) r -NH-C (= 0)-K071 J063 T176 429-(CH2) 2- &gt; NH-C (= 0). K072 J012 T148 430-(CH2) 2 --NH-C (= 0)-K072 J012 T152 431-(CH2) 2- -NH-C (= 0)-K072 J029 T148 432-(CH2) r -NH-C (= 0)-K072 J029 T151 433-(CH2) 2- -NH-C (= 0)-K072 J046 T148 434 _ (ch2) 2- -NH-C (= 0) K072 J046 T169 435 _ (ch2) 2- -NH-C ( = 0)-K072 J063 T148 436-(ch2) 2- -NH-C (= 0 K072 J063 T152 437 -NH-C (= 0)-K072 J080 T148 438-(CH2) 2_ -NH-C (= 0)-K072 J080 T151 439-(CH2) 2- -NH-C (= 0)-K072 J081 T178 440-(CH2) 2 · -NH-C (= 0)-K073 J001 T129 441-(CH2) 2_ -NH-C (= 0)-K074 J002 T130 442-(CH2) 2- -NH-C (= 0 Bu K075 J008 T134 443-(CH2) 2- -NH-C (= 0)-K076 J009 T135 444 -(CH2) 2 · -N HC (= 0)-K077 J012 T145 445-(CH2) 2- -NH-C (= 0)-K078 J014 T148 446-(ch2) 2- -NH-C (= 0)-K079 J015 T149 447-( CH2) 2 · -NH-C (= 0)-K080 J018 T151 448-(ch2) 2_ -NH-C (= 0) · K081 J043 T152 449-(ch2) 2 · -NH-C (= 0)- K082 J045 T157 450-(CH2) 2. -NH-C (-O)-K083 J063 T158 -127 (123) Compound number -A1- • A2 · -g1-a3-a4-g2 -A, R2 -a6- r3 451-(ch2) 2- -NH-C (= 0)-K084 J081 T164 452 • (CH2) 2 · -NH-C (= 0) · K085 J001 T168 453-(CH2) 2- -NH-C (= 0)-K086 J002 T169 454-(CH2) 2- -NH-C (= 〇K K087 J008 T170 455-(CH2) 2- -NH-C (= 0)-K088 J009 T173 456-"ch2) 2- -NH-C (= 0) K089 J012 T176 457-(CH2) 2. .NH-C (= 0)-K090 J014 T178 458-(ch2) 2 · -NH-C (= 0)-K091 J015 T129 459-(CH2) 2_ -NH-C (= 0)-K092 J018 T130 460-(CH2) 2- -NH-C (= 0)-K093 J043 T134 461 • (CH2) r -NH-C ( = 0)-K094 J045 T135 462-(CH2) 2- -NH-C (= 0)-K095 J063 T145 463 • (ch2) 2_ -NH-C (= 0) K096 J081 T148 464-(CH2) 2_ -NH-C (= 0)-K097 J001 T149 465-(CH2) 2- -NH-C (= 0)-K098 J002 T151 466-(CH2 &gt; 2. -NH-C (= 0)-K099 J008 T152 467-(C H2) 2- .NH-C (= 0)-K100 J009 T157 468-(CH2) r -NH-C (= 0)-K101 J012 T158 469-(CH2) 2 · -NH-C (= 0)- K102 J014 T164 470-"ch2) 2- -NH-C (= 0) K103 J015 T168 471-(CH2) 2 · -NH-C (= 0)-K104 J018 Ding 169 472-(CH2) r -NH -C (= 0)-K105 J043 T170 473-(CH2) 2 · -NH-C (= 0)-K106 J045 T173 474-(CH2) 2 · -NH-C (= 0)-K107 J013 T148 475 • (CH2) r -NH-C (= 0)-K107 J013 T169 -128- 200526665 (124) Compound number -A1--A2 · -g, a3-a4-g2 -As-R2 -Ae-R3 476-( CH2) 2- -NH-C (= 0)-K107 J030 T148 477-(CH2) r -NH-C (= 0)-K107 J030 T152 478-(CH2) 2- • NH-C (= 0)- K107 J047 T148 479-(CH2) 2_ -NH-C (= 0)-K107 J047 T151 480 • (ch2) 2- -NH-C (= 0)-K107 J063 T176 481-(ch2) 2- • NH- C (= 0) _ K107 J064 T148 482-(CH2) 2- -NH-C (= 0) &gt; K107 J064 T169 483-(CH2) r -NH «C (= 0)-K107 J081 T148 484-( CH2): r -NH-C (= 0)-K107 J081 T152 485-(CH2) 2- -NH-C (= 0)-K108 J008 T148 486 _ (CH2) r -NH-C (= 0)- K108 J009 T148 487-(CH2) 2- -NH-C (= 0)-K108 J012 T148 488 ， (CH2) 2 · -NH-C (= 0)-K108 J014 T148 489-(CH; 2) 2_- NH-C (= 0)-K 108 J014 T151 490-(CH2) 2- -NH-C (= 0)-K108 J031 T148 491-(CH2) 2- -NH-C (= 0)-K108 J031 T169 492-(CH2) 2. -NH -C (= 0). K108 J045 T148 493-(CH2) 2_ -NH-C (= 0)-K108 J048 T148 494-(ch2) 2- -NH-C (= 0)-K108 J048 T152 495-( CH2) 2- .NH-C (= 0)-K108 J065 T148 496-(CH2) 2. -NH-C (= 0)-K108 J065 T151 497-(CH2) 2- -NH.C (= 0) K108 J081 T178 498 _ (ch2) 2- -NH-C (= 0). K108 J082 T148 499 • (CH2) 2- -NH-C (= 0)-K108 J082 T169 500-(CH2) 2 · • NH-C (= 0)-K109 J001 T129

129- (125) Compound number -A1- -A2- -G, A3-Aa-G2 -a5-r2 -a6-r3 501-(CH2) 2- • NH_C (= 0)-K109 J008 T148 502 • (ch2 ) 2- -NH-C (= 0)-K109 J009 T148 503-(CH2) r -NH-C (= 0)-K109 J012 T148 504-(CH2) 2. -NH-C (= 0) K109 J045 T148 505-(CH2) 2- -〇 (= 〇) K110 J002 T130 506-(CH2) 2- -NH-C (= 0)-K111 J008 T134 507-(CH2) 2- -NH-C ( = 0)-K112 J009 T135 508-(CH2) 2, -NH-C (= 0)-K113 J012 T145 509-(ch2) 2- -NH-C (= 0)-K114 J014 T148 510-(CH2) 2- -NH-C (= 0)-K115 J015 T149 511-(CH2) 2- • NH-C (= 0) K116 J018 T151 512-(ch2) 2. -NH-C (= 0). K117 J043 T152 513 • (CH2) 2, -NH-C (= 0)-K118 J045 T157 514-(CH2) r -NH-C (= 0)-K119 J063 T158 515-(CH2) 2 · -NH-C (= 0)-K120 J081 T164 516-(CH2) 2- -NH-C (= 0)-K121 Guang J001 T168 517-(CH2) 2- -NH-C (= 0)-K122 J002 T169 518-( CH2) 2- -NH-C (= 0)-K123 J008 T170 519 _ (CH2) 2 · -NH-C (= 0)-K124 J009 T173 520-(CH2) 2- -NH-C (= 0) K125 J012 T176 521-(ch2) 2. -NH-C (= 0)-K126 J014 T178 522-(CH2) 2- • NH-C (= 0) _ K127 J015 T129 523 • (CH2) 2 ·- NH-C (; 0)-K128 J018 T130 524-(CH2) 2- • NH-C (= 0)-K129 J043 T134 525 • (CH2) r -NH-C (= 0). K130 J045 T135 • 130- 200526665 (126) Compound No.-A1 -A2- .g1-a3-a4-g2 -A, R2 -a6-r3 526-(ch2) 2- -NH-C (= 0)-K131 J063 T145 527-(CH2) 2- -NH-C (= 0)-K132 J081 Ding 148 528-(CH2) 2 · NH-C (= 0)-K133 J001 T149 529-(ch2) 2- -NH-C (= 0)-K134 J002 T151 530-( ch2) 2- -NH-C (= 0)-K135 J008 T152 531-(ch2) 2 · -NH-C (= 0)-K136 J009 T157 532-(CH; 2) 2- -NH-C (= 0)-K137 J008 T148 533-(CH2) 2- -NH-C (= 0)-K137 J009 T148 534-(CH2) 2- -NH-C (= 0)-K137 J012 T148 535 • (ch2) 2_ -NH-C (= 0)-K137 J012 T158 536 -NH-C (= 0) K137 J045 T148 537-(CH2) 2- -NH-C (= 0)-K138 J014 T164 538-(CH2) 2 --NH-C (= 0)-K139 J015 T168 539-(CH2) 2 · -NH-C (= 0)-K140 J018 T169 540-(ch2) 2- -NH-C (= 0)-K141 J043 T170 541-(CH2) 2- -NH-C (= 0)-K142 J045 T173 542-(ch2) 2- -NH-C (= 0)-K143 J063 T176 543 _ (ch2) 2- -NH-C (= 0)-K144 J008 T148 544-(CH2) 2- -NH-C (= 0)-K144 J009 T148 545 • (CH2) 2- • NH-C (= 0)-K144 J012 Ding 148 546-( CH2) 2- • NH-C (= 0)-K144 J015 T148 547-(CH2) 2_ -NH-C (= 0)-K144 J015 Ding 152 548 • (CH2) 2 · -NH ^ C (= 0)-K144 J032 T148 549-(CH2) 2- -NH-C (= 0)-K144 J032 T151 550-(ch2) 2. -NH-C (= 0)-K144 J045 T148 -131 (127) Compound No.-A1--A2 --gW-g2 -A, R2 -a6-r3 551-(CH2) 2- -NH'C (= 0)-K144 J049 T148 552-(CH2) 2. -NH-C (= 0)-K144 J049 T169 553-(CH2) 2- -NH-C (= 0) K144 J066 T148 554-(CH2) 2- -NH-C (= 0)-K144 J066 T152 555 • (ch2) 2- -NH-C (= 0) K144 J081 T178 556-(CH2) 2_ -NH-C (= 0)-K144 J083 T148 557-(CH2) 2- -NH-C (= 0)-K144 J083 T151 558-(CH2) 2- -NH-C (= 0) K145 J001 T129 559-(CH2) 2- -NH-C (= 0)-K146 J002 T130 560-(CH2) 2 · -NH.C (= 0)-K147 J008 T134 561-(CH2) 2. -NH-C (= 0). K148 J009 T135 562-(CH2) 2- -NH-C (= 0). K149 J012 T145 563-(ch2) 2. -NH- C (= 0)-K150 J014 T148 564-(CH2) 2- -NH-C (= 0)-K151 J015 T149 565-(CH2) 2- -NH-C (= 0)-K152 J018 Ding 151 566- (CH2) 2- -NH-C (= 0)-K153 J043 T152 567, (CH2) r -NH-C (= 0)-K154 J045 T157 568-(CH2) 2 · -NH-C (= 0) -K155 J063 T158 569-(CH2) r -NH-C (= 0)-K1S6 J081 T164 570-(CH2) 2- -NH-C (= 0)-K157 J001 T168 571-(CH2) 2- -NH-C (= 0)-K158 J002 T169 572-(ch2) 2- -NH-C (= 0). K159 J008 T170 573-(CH2) r -NH-C (= 0). K160 J009 T173 574 • (CH: 2) 2- • NH-C (= 0), K161 J012 T176 575-(CH2> 2- -NH-C (= 0)-K162 J014 T178 -132- (128) Compound number -A1--A2- -G, A3-A4-G2- a5_r2 -A, R3 576-(ch2) 2- -NH-C (= 0)-K163 J015 T129 577 _ (CH2) 2- • c (= o) K164 J018 T130 578-(ch2) 2- &gt; NH-C (= 0)-K165 J043 T134 579, (ch2) 2_ -NH-C (= 0)-K166 J045 T135 580-(CH2> 2- -NH-C (= 0)-K167 J063 T145 581- (ch2) 2_ -NH-C (= 0)-K168 J081 T148 582-(CH2) 2, -NH-C (= 0). K169 J001 T149 583-(CH2) 2- -NH-C (= 0) -K170 J002 T151 584-(CH2) 2- -NH-C (= 0)-K171 J008 T152 585-(ch2) 2 · -NH-C (= 0) · K172 J009 T157 586-(CH2) 2-- NH-C (= 0)-K173 J012 T158 587-(ch2) 2- -NH-C (= 0). K174 J014 T164 588 • (ch2) 2- -NH-C (= 0)-K175 J015 T168 589 -(CH2) 2. -NH-C (= 0)-K176 J018 T169 590-(CH2) 2 '-NH-C (= 0)-K177 J043 T170 591-(ch2) 2 · -NH-C (= 0)-K178 J045 T173 592-(CH2) 2. -NH-C (= 0)-K197 J063 T176 593 (ch2) 2- -NH-C (= 0)-K198 J008 T148 594, (ch2) 2- -NH-C (= 0). K198 J009 Ding 148 595-(ch2) 2- -NH-C (= 0). K198 J012 T148 596-(ch2) 2_ -NH-C (= 0)-K198 J045 T148 597-(ch2) 2 --NH-C (= 0)-K198 J081 T178 598-(CH2) 2- .NH-C (= 0)-K199 J001 T129 599-(CH2) 2_ -NH-C (= 0) K199 J008 T148 600 • "ch2) 2 · -NH-C (= 0). K199 J009 T148 -133- 200526665 (129) Compound number -A1- -A2- -g, a3-a4_g2 -As-R2 -a6-r3 601 • (ch2) 2 · -NH-C (= 0)-K199 J012 T148 602-(ch2) 2- -NH-C (= 0)-K199 J045 T148 603-(CH2) 2- -NH-C (= 0 )-K200 J002 T130 604-(ch2) 2- -NH-C (= 0)-K200 J008 T005 605-(CH2) 2- -NH-C (= 0)-K200 J008 T148 606-(CH2) 2_- NH-C (= 0)-K200 J008 T151 607-(CH2) 2- -NH-C (= 0)-K200 J008 T152 608-(CH2) 2- -NH-C (= 0)-K200 J008 T169 609 -(CH2) 2- -NH-C (= 0)-K200 J009 T005 610-(CH2) 2. -NH-C (= 0)-K200 J009 T148 611-(CH2) 2 · -NH-C (= 0)-K200 J009 T151 612 • (ch2) 2 · -NH-C (= 0)-K200 J009 T152 613-(ch2) 2- -NH-C (= 0)-K200 J009 Ding 169 614 • (C &quot; 2) 2 -N HC (= 0)-K200 J012 T005 615-(CH2) 2 · NH-C (= 0)-K200 J012 T148 616-(CH2) 2- -NH-C (= 0)-K200 J012 T151 617-( ch2) 2 · -NH-C (= 0)-K200 J012 T152 618-(CH2) 2- -NH-C (= 0)-K200 J012 T169 619-(CH2) r -NH-C (= 0)- K200 J016 T005 620-(CH2) 2- -NH-C (= 0)-K200 J016 T148 621 _ (ch2) 2- -NH-C (= 0). K200 J016 T169 622-(CH2) 2 · -NH -C (= 0)-K200 J033 T005 623-(ch2) 2 · -NH-C (= 0)-K200 J033 T148 624-(CH2) 2- -NH-C (= 0)-K200 J033 T152 625- (CH2) 2--NH-C (= 0) K200 J045 T005

-134- 200526665 (130) Compound No.A1 · -A2 · -g1-a3-a4-g2 -a5-r2 -a6-r3 626-(CH2) 2- -NH-C (= 0) &gt; K200 J045 T148 627-(CH2) 2- -NH-C (= 0)-K200 J045 T151 628-(CH2) 2 · -NH-C (= 0)-K200 J045 T152 629-(CH2) 2- • NH-C (= 0)-K200 J045 T169 630-(CH2) r -NH ~ C (= 0)-K200 J050 T148 631 • (ch2) 2- -NH-C (= 0)-K200 J050 T151 632-(CH2) 2- -NH-C (= 0)-K200 J067 T148 633-(ch2) 2--c (= o)-K200 J067 T169 634-(CH2) 2- -NH-C (= 0)-K200 J084 T148 635 _ (CH2> 2, -NH-C (= 〇)-K200 J084 T152 636-(ch2) 2- -NH-C (= 0)-K201 J008 T134 637-(CH2) 2_ -NH-C (= 0)-K202 J009 T135 638-(CH2) 2- -NH-C (= 0)-K203 J008 T148 639 _ (CH2) 2- -NH-C (= 0)-K203 J009 T148 640-(ch2) 2 --NH-C (= 0)-K203 J012 T145 641-(CH2) 2, -NH-C (= 0)-K203 J012 T148 642-(CH2) r -NH-C (= 0)-K203 J017 Ding 148 643-(CH2) 2. -NH-C (= 0)-K203 J017 T151 644-(CH2) r -NH-C (= 0)-K203 J034 T148 645 ** (CH2) 2- -NH-C (= 0)-K203 J034 T169 646-(ch2) 2. -NH-C (= 0)-K203 J045 T148 647-(CH2) 2- -NH-C (= 0)-K203 J051 T148 648-(CH2 ) r -NH-C (= 0). K 203 J051 T152 649-(ch2) 2- .NH-C (= 0)-K203 J068 T148 650-(CH2) 2- -NH-C (= 0)-K203 J068 T151 -135- 200526665 (131) Compound number -A1- -A2- -g, a3-a4-g2 -AS.R2 -a6-r3 651 • (CH2) r • NH-C (= 0)-K203 J085 T148 652-(CH2) r -NH-C (= 0)-K203 J085 T169 653-(CH2) 2- -NH-C (= 0)-K204 J014 T148 654 • (CH2) 2 ~ -NH-C (= 0)-K205 J015 T149 655-(CH2 ) 2- -NH-C (= 0)-K206 J008 T148 656-(CH2) r -NH-C (= 0). K206 J009 T148 657-(CH2> 2- .NH-C (= 0)-K206 J012 T148 658-(CH2) 2- -NH-C (= 0)-K206 J018 T151 659-(CH2) 2. -NH-C (= 0> K206 J045 T148 660-(CH2) 2- -NH- C (= 0)-K207 J008 T148 661-(CH2) 2- -NH-C (= 0)-K207 J009 T148 662-(ch2) 2- -NH-C (= 0)-K207 J012 T148 663-( CH2) 2- -NH-C (= 0)-K207 J043 T152 664-(CH2) 2- -NH-C (= 0)-K207 J045 T148 665-(CH2) 2 · -NH-C (= 0) K208 J008 T148 666-(CH2) 2- -NH-C (= 0)-K208 J009 T148 667-(CH2) 2- -NH-C (= 0)-K208 J012 T148 668-(CH2) 2.-- NH-C (= 0). K208 J045 T148 669 • (CH2) 2- -NH-C (= 0)-K208 J045 T157 670-(CH2) r -NH ”C (= 0) · K209 J008 T148 671- (ch2) 2-- NH-C (= 0)-K209 J009 T148 672-(CH2) r -NH-C (= 0). K209 J012 T148 673-(CH2) 2 · -NH-C (= 0)-K209 J045 T148 674- (CH2) 2- -NH-C (= 0)-K209 J063 T158 675 • (ch2) 2- -NH-C (= 0)-K210 J008 T148 -136- 200526665 (132) Compound No.-A1- -A2 · -G1-a3-a4-g2 -As-R2 -a6-r3 676-(CH2) 2- -NH ， C (= 0)-K210 J009 T148 677 ， (CH2) 2_ -NH-C (= 0) -K270 J012 T148 678-(CH2) 2- -NH-C (= 0)-K210 J045 T148 679-(ch2) 2- -NH-C (= 0)-K210 J081 T164 680 _ (ch2) 2-- NH-C (= 0)-K211 J001 T168 681-(CH2) 2- -NH-C (= 0)-K211 J008 T148 682-(CH2) 2- -NH-C (= 0). K211 J009 T148 683 -(CH2) 2 · -NH-C (= C〇- K211 J012 T148 684 _ (ch2) 2- -NH-C (= 0)-K211 J045 T148 685-(CH2) 2.-NH-C (= 0)-K212 J002 Ding 169 686-(CH2) 2- -NH-C (= 0)-K212 J008 T148 687-(ch2) 2 · • NH-C (= 0)-K212 J009 T148 688 • (CH2) 2 · -NH-C (= 0) · K212 J012 T148 689 -NH-C (= 0)-K212 J045 T148 690-(CH2) 2 · -NH-C (= 0)-K213 J008 T170 691 &quot; ( CH2) 2- -NH-C (= 0)-K214 J009 T173 692 • (CH2) 2 · -NH-C (= 0)-K215 J008 T148 693 • (CH2) 2- -NH-C (= 0) -K215 J009 T 148 694-(ch2) 2- -NH-C (= 0). K215 J012 T148 695 • (ch2) 2- • NH-C (= 0)-K215 J012 T176 696 _ (CH2) r -NH-C ( = 0). K215 J045 T148 697-(CH2) 2- -NH-C (= 0)-K216 J014 T178 698-(CH2) 2- -NH-C (= 0)-K217 J015 T129 699 _ (CH2> 2. · NH-C (= 0)-K218 J018 T130 700-(CH2) 2- .NH-C (= 0). K219 J008 T148 -137- (133) Compound No.A1- -A2- _g, a3 -a4-g2 -a5-r2 -a6-r3 701-(CH2) 2- -NH-C (= 0)-K219 J009 T148 702-(ch2) 2- -NH-C (= 0)-K219 J012 T148 703-(CH2) 2- -NH, C (= 0)-K219 J043 T134 704-(CH2) 2- -NH-C (= 0)-K219 J045 T148 705-(CH2) 2- -NH-C ( = 0)-K220 J008 T148 706-(CH2) 2- -NH-C (= 0)-K220 J009 T148 707 • (CH2) 2 · -NH-C (= 0)-K220 J012 T148 708-(CH2) 2- -NH-C (= 0)-K220 J045 T135 709-(ch2) 2- -NH-C (= 0)-K220 J045 T148 710-(CH2) 2. -NH-C (= 0)-K221 J008 T148 711-(CH2) 2- -NH-C (= 0)-K221 J009 T148 712-(ch2) 2- -NH-C (= 0)-K221 J012 T148 713-(CH2) 2- -NH- C (= 0)-K221 J045 T148 714-(CH2) 2- -NH-C (= 0)-K221 J063 T145 715-(CH2) 2 · -NH-C (= 0)-K222 J008 T148 716-( CH2) 2 · -NH-C (= 0)-K222 J00 9 T148 717 • (CH2) 2- -NH-C (= 0)-K222 J012 T148 718 • (CH2) 2_ -NH-C (= 0)-K222 J045 T148 719-(CH2) 2 · -NH-C (= 0)-K222 J081 T148 720-(ch2) 2- -NH-C (= 0)-K223 J001 T149 721-(ch2) 2- -NH-C (= 0)-K223 J008 T148 722-(CH2 ) 2--NH-C (= 0)-K223 J009 T148 723-(ch2) 2- -NH-C (= 0)-K223 J012 T148 724-(CH2) 2 · -NH-C (= 0)- K223 J045 T148 725 • (CH2) r -NH-C (= 0) K224 J002 T151 -138 20052005665 (134) Compound number -A1- -A2- -g, a3-a4-g2 -a5-r2 -A , R3 726-(CH2) 2- -NH-C (= 0)-K224 J008 T148 727-(CH2〉 2- -NH-C (= 0)-K224 J009 T148 728-(CH2) 2- -NH- C (= 0). K224 J012 T148 729-(ch2) 2- -NH-C (= 0)-K224 J045 T148 730-(CH2) 2- -NH-C (= 0) K225 J008 T148 731-( ch2) 2- -NH-C (= 0)-K225 J008 T152 732-(CH2) 2- -NH-C (= 0)-K225 J009 T148 733-(CH2) 2- -NH-C (= 0) -K225 J012 T148 734-(CH2) 2- -NH-C (= 0)-K225 J045 T148 735 -NH-C (= 0)-K226 J009 T157 736-(CH2) 2- • NH-C (= 0 )-K227 J012 T158 737-(CH2) 2- -NH-C (= 0)-K228 J008 T148 738 • (CH2) 2_ -NH-C (= 0)-K228 J009 T148 739 _ (CH2) 2 ·- NH-C (= 0)- K228 J012 T148 740-(CH2) 2- -NH-C (= 0) &gt; K228 J014 T164 741 • (ch2) 2- -NH-C (= 0)-K228 J045 T148 742-(ch2) 2-- NH-C (= 0)-K229 J015 T168 743 • (ch2) 2- -NH-C (= 0)-K230 J018 T169 744 • (ch2) 2- -NH-C (= 0)-K231 J043 T170 745 -(CH2) 2- -NH-C (= 0)-K232 J045 T173 746 _ (ch2) 2- -NH-C (= 0)-K233 J063 T176 747-(CH2) 2- -NH-C (= 〇V K234 J081 T178 748-(CH2) 2_ • NH-C (= 0) K235 J012 T148 749-(CH2) 2_ -NH-C (= 0) K236 J045 T148 750-(CH2) r -NH- C (= 0) -NHK003 J002 T148

-139- (135) Compound number -A1- -A2- -g, a3-a4-g2 • a6-r2 -a6-r3 751-(CH2) 2, -NH-C (= 0) -NH- K003 J002 T151 752-(CH2) 2 · -NH-C (= 0) -NH- K003 JOOB T148 753-(ch2) 2- -NH-C (= 0) -NH- K003 J008 T151 754-(CH2) r- NH> C (= 0) -NH- K003 J008 T152 755 _ (CH2) 2_ -NH-C (= 0) -NH- K003 J008 T169 756-(CH2) 2 · -NH-C (= 0) -NH -K003 J009 T148 757-(CH2) 2- -NH-C (= 0) -NH- K003 J009 T151 758-(CH2) 2_ -NH-C (= 0) -NH- K003 J009 T152 759-(CH2) 2- -NH.C (= 0) -NH- K003 J009 T169 760-(CH2) 2- -NH-C (= 0) -NH- K003 J012 T148 761-(CH2) 2 · -NH-C (= 0) -NH- K003 J012 T151 762-(CH2) 2_ • NH-C (0) -NH- K003 J012 T152 763-(CH2) 2- • NH-C (= 0) _NH- K003 J012 T169 764-( CH2) 2- -NH-C (= 0) -NH- K003 J019 T148 765 _ (CH2) 2- -NH-C (= 0) -NH- K003 J019 T169 766-(CH2) r -NH-C ( = 0) -NH- K003 J036 T148 767-(CH2) 2 · -NH-C (= 0) -NH- K003 J036 T152 768 _ (ch2) 2- -NH-C (= 0) -NH- K003 J045 T148 769-(ch2> 2 · -NH-C (= 0) -NH- K003 J045 T151 770-(〇h2) 2. -NH-C (= 0) -NH- K003 J045 T152 771-(CH2 &gt; 2 --NH-C (= 0) -NH- K003 J045 T169 772 • (CH 2) 2 · -NH-C (= 0) -NH- K003 J053 T148 773-(CH2〉 2- • MH-C (= 0) -NH- K003 J053 T151 774-(CH2) 2 · -NH-C (= 0) -NH- K003 J070 T148 775-(ch2) 2- -NH-C (= 0) -NH- K003 J070 T169 -140- 200526665 (136) Compound No.-A1- -A2- .q ^ A ^ A ^ G2 -a5-r2 -Ae-R3 776 • (CH2) 2- -NH-C (= 0) -NH- K009 J045 T148 777, (ch2) 2- -NH-C (= 0) -NH -K012 J008 T148 778-(CH2) 2. -NH-C (= 0) -NH- K012 J008 T151 779-(CH2) 2- -NH-C (= 0) -NH- K012 J008 T152 780-(CH2 ) 2_ -NH-C (= 0) -NH- K012 J008 T169 781-(ch2) 2- -NH-C (= 0) -NH- K012 J009 T148 782-(CH2) 2- -NH-C (= 0) -NH- K012 J009 T151 783-(CH2) 2. -NH-C (= 0) -NH- K012 J009 T152 784-(CH2) 2- • NH-C (= 0) -NH- K012 J009 T169 785 • (ch2) 2- -NH-C (= 0) -NH- K012 J012 T148 786 _ (CH2) 2- -NH-C (= 0) -NH- K012 J012 T151 787-(CH2) 2-- NH-C (= 0) -NH- K012 J012 T152 788-(CH2) 2- -NH-C (= 0) -NH- K012 J012 T169 789-(CH2) 2- -NH-C (= 0)- NH- K012 J026 T148 790-(CH2) 2- -NH-C (= 0) -NH- K012 J026 T151 791 _ (ch2) 2- -NH-C (= 0 &gt; NH- K012 J043 T148 792-(ch2 ) 2- -NH-C (= 0) -NH- K012 J043 T169 793-(CH2) 2. -NH- C (= 0) -NH- K012 J045 T148 794 • (CH2) 2- -NH-C (= 0) -NH- K012 J045 T151 795-(CH2) 2 · • NH-C (= 0) -NH- K012 J045 T152 796-(CH2) 2, -NH-C (= 0) -NH- K012 J045 T169 797-(CH2) 2- -NH-C (= 0) -NH- K012 J060 T148 798 • (ch2) 2- -NH-C (= 0) -NH- K012 J060 T152 799-(CH2> 2- -NH-C (= 0) -NH- K012 J077 T148 800 • (ch2) 2 · -NH-C (= 0) -NH- K012 J077 T151

-141-200526665 (137) Compound number -A1- -A2- -G ^ A ^ A'-G2 -As-R2 -A6-R3 801-(ch2) 2- -NH-C (= 0) -NH- K013 J045 T148 802 • (ch2) 2 · -NH-C (= 0) -NH- K014 J045 .Ding 148 803-(ch2) 2- -NH-C (= 0) -NH- K017 J045 T148 804-( ch2) 2 · -ΝΗ-0 (= 0) -ΝΗ- K032 J045 T148 805-(ch2) 2- -NH-C (= 0) -NH- K229 J045 T148 806-(ch2) 2- • NH-C (= 0) -NhlK230 J045 T148 807-(CH2) 2- -NH-C (= 0) -NH- K231 J045 T148 808 • (CH2) r -NH-C (= 0) -NH- K232 J045 T148 809-(CH2) 2_ -NH-C (= 0) -NH- K233 J045 T148 810-(CH2) 2_ -NH-C (= 0) -NH- K234 J045 T148 811-(CH2) 2- -NH -C (= 0) -NH- K235 J045 T148 812 • (CH2) 2- • NH-C (= 0) -NH- K236 J045 T148 813-(CH2) 2- -NH-C (= 0) -0 -K005 J001 T001 814-(ch2) 2- NH-C (= 0) -0 · K005 J001 T005 815-(CH2) 2 · -NH-C (= 0) -0- K005 J001 T010 816-(CH2) r • NH-C (= 0) -0- K005 J001 T019 817-(ch2) 2- -NH-C (= 0) -0- K005 J001 T028 818-(CH2) 2- -NH-C (= 0 ) -0- K005 J001 T037 819-(CH2) 2- -NH-C (= 0〉 -0- K005 J001 T046 820 _ (ch2) 2--NH-C (= 0) -0- K005 J001 T055 821 -(ch2) 2- -NH-C (= 0) -0- K005 J001 T064 822 (ch2) 2- • c (= o) -o · K005 J001 T073 823-(CH2) 2. -NH-C (= 0) -0- K005 J001 T082 824-(CH2) 2- -NH-C ( = 0) -0- K005 J001 T091 825 • (ch2) 2_ -NH-C (= 0). K005 J001 T100 -142- (138) Compound number-A1- • A2- -g1-a3-a, g2 -a5-r2 -a6-r3 826-(CH2) 2 · -NH-C (= 0) -0- K005 J001 T109 827-(CH2) 2_ -NH-C (= 0) -0- K005 J001 T118 828-(CH2) 2_ -NH-C (= 0) -0- K005 J001 T127 829-(CH2) 2- • NH-C &lt; = 0) -0- K005 J001 T136 830-(ch2) 2- -NH -C (= 0) -0- K005 J001 T145 831-(CH2) 2- -NH-C (= 0) -0- K005 J001 T154 832-(ch2) 2- -NH-C (= 0) -0 -K005 J001 T163 833-(CH2) 2- -NH-C (= 0) -0- K005 J001 T172 834-(ch2) 2. -NH-C (= 0) -0- K005 J002 T002 835-(CH2 ) 2_ -NH-C (= 0) -0- K005 J002 T011 836-(CH2) 2- -NH-C (= 〇H &gt; K005 J002 T020 837-(CH2) r -NH-C (= 0)- 0- K005 J002 T029 838 _ (CH2) 2- -NH-C (= 0) -0 · K005 J002 T038 339-(CH2) 2- -NH-C (= 0) -0- K005 J002 T047 840-( CH2) 2- -NH-C (= 0) -0- K005 J002 T056 841-(CH2) 2 ~ -NH-C (= 0) -0- K005 J002 T065 842-(CH2) 2 · -NH-C (= 0) -0- K005 J002 T074 843-(CH2) 2_ -NH-C (= 0) -〇. K005 J002 T 083 844-(CH2) 2- • NH-C (= 0) -0- K005 J002 T092 845-(ch2) 2- -NH-C (= 0) -0- K005 J002 T101 846-(CH2) r- NH'C (= 0) -0- K005 J002 T110 847-(CH2) 2- -NH-C (= 0) -0- K005 J002 T119 848-(CH2) r -NH-C (= 0) -0 K005 J002 T128 849 • (CH2) 2. -NH-C (= 0) -0- K005 J002 T137 850-(CH2) 2- .NH-C (= 0) -0- K005 J002 T146 -143- 200526665 (139) Compound number -A1--A2- -g1-a3-a4-g2 • a5-r2 -a6-r3 851-(CH2) 2- • c (= o) -o- K005 J002 T155 852-(ch2 ) 2- -NΗ · 0 (= Ο) · Ο · K005 J002 T164 853-(CH2) 2, -NH-C (= 0) -0- K005 J002 T173 854, (CH2) r. -NH-C ( = 0) -0 · K005 J008 T003 855-(CH2) 2- -NH-C (= 0) -0- K005 J008 T005 856-(CH2) 2 · -NH-C (= 0) -0- K005 J008 T012 857 • (CH2) 2- -NH-C (= 0) -0- K005 J008 T021 858-(ch2) 2 · -NH-C (= 0) -0- K005 J008 T030 859-(CH2) 2 ~ -NH-C (= 0) -0- K005 J008 T039 860 • (ch2) 2- -NH-C (= 0) -0- K005 J008 T048 861-(ch2) 2- -NH-C (= 0) -0- K005 J008 T057 862-(CH2) 2- • NH-C (= 0) -0- K005 J008 T066 863-(ch2) 2. • NH-C (= 0) -0- K005 J008 T075 864- (CH2) 2 · -NH-C (= 0) -0- K005 J008 T084 865-(C H2) 2. -NH-C (= 0) ~ 0K005 J008 T093 866-(CH2) 2- -NH-C (= 0) -0- K005 J008 T102 867-(ch2) 2- -NH-C (= 0) -0- K005 J008 T111 868-(CH2) 2- -NH-C (= 0) -0- K005 J008 T120 869-(CH2) r • NH-C (= 0) -0- K005 J008 T129 870 _ (CH2) 2- -NH-C (= 0) -0- K005 J008 T138 871-(ch2) 2 · -NH-C (= 0) -0 · K005 J008 T147 872-(CH2) 2- -NH-C (= 0) -0- K005 J008 T156 873-(CH2) 2 ..NH-C (= 0) -0- K005 J008 T165 874-(ch2) 2 · -NH-C (= 0) -0- K005 J008 T174 875 • (CH2) 2- -NH-C (= 0) -0- K005 J009 T004

-144- (140) Compound number -A1--A2- -g, a3-a4-g2 -AW -A, R3 876-(CH2) 2- -NH-C (= 0)-0- K005 J009 T005 877 -(ch2) 2_ -NH-C (= 0) -0- K005 J009 T013 878 _ (CH2) 2 ~ • NH-C (= 0) -0- K005 J009 T022 879 • (ch2) 2- -NH_C ( = 0) -0- K005 J009 T031 880-(CH2) 2- -NH-C (= 0) -0- K005 J009 T040 881-(CH2) 2 · -NH-C (= 〇H &gt; K005 J009 T049 882 _ (CH2) 2, -NH-C (= 0) -0- K005 J009 T058 883-(CH2) 2 · -NH-C (= 0) -0- K005 J009 T067 884-(ch2) 2- -NH -C (= 0) -0- K005 J009 T076 885-(CH2) 2- -NH-C (= 0) -0- K005 J009 T085 886-(CH2) 2- -NH-C (= 0) -0 -K005 J009 T094 887 _ (ch2) 2- -nh-c (= o) -o_ K005 J009 T103 888-(CH2) 2. -NH-C (= 0) -0- K005 J009 T112 88Θ-(CH2) 2- -NH-C (= 0) -0- K005 J009 T121 890-(ch2) 2- -NH-C (= 0) -0- K005 J009 T130 891-(CH2) 2 · -NH-C (= 0) -0- K005 J009 Ding 139 892-(ch2) 2- -NH-C (= 0) -0- K005 J009 T148 893-(ch2) 2. • NH-C (= 0) -0- K005 J009 T157 894-(CH2) 2- -NH-C (= 0) -0- K005 J009 T166 895-(CH2) 2- -NH-C (= 0) -0- K005 J009 T175 896-(ch2) 2- • NH-C (= 0) -0- K005 J012 T005 897-(CH2> 2_ -NH-C (= 0) -0- K0 05 J012 T014 898-(ch2) 2- -NH-C (= 0) -0- K005 J012 T017 899 • (CH2) r -NH-C (= 0) -0- K005 J012 T023 900-(CH2) 2 --NH-C (= 0) -0- K005 J012 T032 -145- (141) Compound No.-A1- -A2- -G, A3-A4- G2 _A, R2 -a6-r3 901-(CH2) r -NH-C (= 0) -O K005 J012 T041 902-(CH2) 2- -NH-C (= 0) -0- K005 J012 T050 903-(CH2) 2- -NH-C (= 0)- 0- K005 J012 T055 904-(CH2) 2- -NH-C (= 0) -0- K005 J012 T0S9 905 _ (ch2) 2- -NH-C (= 0) -0- K005 J012 T068 906-( ch2) 2 · -NH-C (= 0) '0- K005 J012 T077 907-(CH2) 2- -NH-C (= 0) -0- K005 · J012 T086 908 • (CH2) 2- -NH- C (= 0) «0- K005 J012 T095 909-(ch2) 2- -NH-C (= 0) -0- K005 J012 T104 910-(CH2) 2 * -NH-C (= 0). K005 J012 T113 911-(CH2) 2_ _NH-C (= 0) -O K005 J012 T122 912-(ch2) 2- -NH-C (= 0) -0- K005 J012 T129 913-(CH2) 2-- NH-C (= 0) -0- K005 J012 T131 914-(ch2) 2- -NH-C (= 0) -0- K005 J012 T140 915-(CH2) 2 .. -NH-C (= 0) -0- K005 J012 T148 916-(CH2) 2 · -NH-C (= 0) -0- K005 J012 T149 917 • (ch2) 2- -NH-C (= 0) -0- K005 J012 T151 918- (CH2) 2- -NH-C (= 0) -0- K005 J012 T152 919-(CH2) 2- -NH-C (= 〇 H &gt; K005 J012 T158 920-(CH2) 2, -NH-C (= 0) .〇- K005 J012 T167 921-(CH2) 2- -NIH-C (= 0). K005 J012 T176 922 • ( CHJr • C (= 0〉 -0- K005 J043 T005 923-(CH2) 2- -NH-C (= 0) .〇- K005 J043 T006 924-(CH2) 2. -NH-C (= 0) -0- K005 J043 T015 925 • (CH2) 2- • NH_C (= 0) _0- K005 J043 T024 -146- 200526665 (142) Compound number -A1--A2- -ϋΑΛ-G2 -a5-r2 -a6- r3 926-(CH2) 2- -NH-C (= 0) -0- K005 J043 T033 927-(CH2) 2. -NH-C (= 0) -〇. K005 J043 T042 928-(CH2) 2- -NH-C (= 0) -0- K005 J043 T051 929-(CH2) 2 · -NH-C (= 0) -0- K005 J043 T060 930-(CH2) 2- -NH-C (= 0) -0- K005 J043 T069 931-(CH2) 2- -NH-C (= 0) -0- K005 J043 T078 932-(CH2) 2- -NH-C (= 0) -0- K005 J043 T087 933- (CH2) 2- -NH-C (= 0) -0- K005 J043 T096 934-(ch2) 2. • NH-C (; 0) -0- K005 J043 T105 935 • (CH2) 2_ -NH-C (= 0) -0 · K005 J043 T114 936-(CH2) 2- -NH-C (= 0) -0- K005 J043 T123 937-(CH2) 2. -NH-C (= 0) -0- K005 J043 T132 938-(CH2) 2_ • NH-C (= 0) -0 K005 J043 T141 939-(CH2) 2- -NH_C (: 0) -0- K005 J043 T150 940-(CH2) 2- • NH- C (= 0) -0- K005 J0 43 T159 941-(ch2) 2. • NH-C (= 0) -0- K005 J043 T168 942-(CH2) 2- -NH-C (= 0) -0- K005 J043 T177 943-(CH2) 2 -NH ** 0 (= 0) -0 ~ K005 J045 T001 944-(CH2) 2- -NH-C (= 〇HD- K005 J045 T003 945-(CH2) 2- -NH-C (= 0) -0- K005 J045 T004 946-(CH2) 2- -NH-C (= 0) -0- K005 J045 T005 947-(CH2) 2- -NH-C (= 0) -0- K005 J045 T007 948- (CH2) 2- -NH-C (= 0) -0- K005 J045 T008 949 • (CH2) 2- • NH-C (= 0) -0- K005 J045 T016 950-(ch2) 2 · -NH- C (= 0) -0- K005 J045 T017

-147- (143) Compound number -A1- -A2 · -G, A3-A4-G2 -AS.R2 -a6-r3 951-(ch2) 2- -NH-C (= 0) -0- K005 J045 T018 952 • (ch2) 2- -NH-C (= 0) -〇- K005 J045 T019 953-(CH2) 2- -NH-C (= 0) -0- K005 J045 T020 954-(CH2) 2_- NH-C (= 0) -0- K005 J045 T025 955-(CH2) 2- -NH, C (: 〇) -0- K005 J045 T034 956-(CH2) 2- -NH-C (= 0)- 0- K005 J045 T042 957 • (CH2) 2 · -NH-C (= 0) -0- K005 J045 T043 958-(ch2) 2. -NH-C (= 0) -0- K005 J045 T052 959-( CH2) 2- -NH-C (= 0) -0- K005 J045 T055 960-(ch2) 2- -NH-C (= 0) -0- K005 J045 T061 961 • (CH2) r -NH-C ( = 0) _0- K005 J045 T070 962-(CH2) 2- -NH-C (= 0) -0- K005 J045 T077 963-(ch2) 2- -NH-C (= 0) -0- K005 J045 T079 964 • (CH2) 2- -NH-C (= 0) -0- K005 J045 T088 965-(CH2〉 2- -NH-C (= 0) -0- K005 J045 T090 966-(CH2) 2 ·-- NH-C (= 0) -0- K005 J045 T096 967-(CH2) 2_ -NH-C (= 0) -0- K005 J045 T097 968-(ch2) 2 · -NH ~ C (= 0) -0 -K005 J045 T100 969-(CH2) 2- -NH-C (= 0 &gt; '0- K005 J045 T106 970 • (CH2) 2, -NH-C (= 0) -0- K005 J045 T108 971-(CH2 ) 2- -NH-C (= 0) -0- K005 J045 T110 972-(CH2) 2- -c (= o) -o- K005 J045 T111 973-(CH2) 2. -NH-C (= 0) -0- K005 J045 T114 974-(CH2) 2- -NH-C (= 〇H &gt; K005 J045 T115 975-(CH2) 2- -NH-C (= 0) -0- K005 J045 T116 -148- (144) Compound number -A1- -A2- -g1-a3-a4_g2 -As-R2 -a6-r3 976-(CH2) 2-- NH-C (= 0) -0- K005 J045 T118 977-(CH2) 2 · NH-C (= 〇H &gt; K005 J045 T119 978-(CH2) 2- -NH-C (= 0) -0- K005 J045 T121 979-(CH2) 2 · -NH-C (= 0) -0 · K005 J045 T122 980-(CH2) 2- -NH-C (= 0) -0- K005 J045 T123 981-(CH2) 2- -NH-C (= 0) -0- K005 J045 T124 982-(ch2) 2- -NH-C (= 0) -0- K005 J045 T128 983-(CH2) 2- -NH-C (= 0) -0- K005 J045 • T129 984-(CH2) 2- -NH-C (= 0) -0- K005 J045 T130 985 • (ch2) 2- • NH-C (= 0) -O K005 J045 T133 986-(CH2) 2, -NH-C (= 0) -0- K005 J045 T136 987-(CH2〉 2 · -NH ~ C (= 0) -0- K005 J045 T137 988-(CH2) 2-- NH-C (= 〇H)-K005 J045 T138 989-(CH2) 2- -NH-C (= 0) -0- K005 J045 T139 990-(CH2) 2- -NH-C (= 0) -0 -K005 J045 T140 991-(CH2) 2- • NH-C (= 0) -0- K005 J045 T141 992-(CH2) 2- -NH-C (= 0) -0- K005 J045 T142 993 • (ch2 ) 2- -NH-C (= 0) -0- K005 J045 T143 994-(CH 2〉 2- • NH-C (= 0) -0- K005 J045 T144 995-(CH2) r -NH-C (= 0) -0- K005 J045 T145 996-(ch2) 2- -NH-C ( = 0) -0- K005 J045 T146 997-(CH2) 2- • NH-C (= 0) -0- K005 J045 T147 998-(CH2) r -NH-C (= 0) -0- K005 J045 T148 999-(CH2) 2 · -NH-C (= 0) -0- K005 J045 T149 1000 • (CH2) r -NH-C (= 0) -0- K005 J045 T150 -149- 200526665 (145) Compound number -A1- -A2- -g, a3-a4-g2 -a5-r2 -a6-r3 1001-(CH2) 2- -NH-C (= 0) -0 · K005 J045 T151 1002 _ (CH2) 2- -NH-C (= 0) -0- K005 J045 T152 1003-(ch2) 2- -NH-C (= 0) -0- K005 J045 T153 1004-(CH2) 2- • NH-C (= 0) -0- K005 J045 T154 1005-(ch2) 2- -NH-C (= 0) -0- K005 J045 T155 1006-(CH2) 2- • NH-C (= 〇H &gt; K005 J045 T156 1007-(CH2 ) 2- -NH-C (= 0) -0- K005 J045 T157 1008-(CH2) 2- -NH-C (= 0) -0- K005 J045 T158 1009-(ch2) 2- -NH-C ( = 0) -0- K005 J045 T159 1010 -NH-C (= 0) -0- K005 J045 T160 1011-(CH2) 2- -NH-C (= 0) -0- K005 J045 T162 1012-(CH2) 2- -NH-C (= 0) -0- K005 J045 T163 1013-(CH2) 2 · -NH-C (= 0) -0- K005 J045 T167 1014 _ (ch2) 2- ^ NH-C (= 0) -0- K005 J045 T169 1015-(CH2) 2- -NH-C (= 0) -0 · K005 J045 T178 1016-(CH2) 2 · • C (= 0) -0- K005 J063 T008 1017-(ch2) 2 · -NH-C (= 0) -0 · K005 J063 T017 1018-(CH2) 2- -NH-C (= 0) -0- K005 J063 T026 1019-(ch2) 2- -NH-C (= 0) -0- K005 J063 T035 1020-(ch2) 2- -NH-C (= 0) -0- K005 J063 T044 1021-(ch2) 2 · -NH-C (= 0) -0- K005 J063 T053 1022-(CH2) 2- -NH-C (= 0) -0- K005 J063 T062 1023 • (ch2) 2. -NH-C (= 0) -0- K005 J063 T071 1024-(CH2) 2- -NH-C (= 0) -0- K005 J063 T080 1025-(ch2) 2- -NH- C (= 0) -0- K005 J063 T089 -150- 200526665 (146) Compound No.-A1- -A2- -G1 -A ^ -A ^ -G ^ -As-R2 -A, R3 1026 • (ch2) 2- -NH-C (= 0) -0 · K005 J063 T098 1027-(CH2) 2- -NH-C (= 0) -0- K005 J063 T107 1028-(CH2) 2- -NH-C (= 0) -0- K005 J063 T116 1029-(CH2) 2 · NH_C (= 0) -0- K005 J063 T125 1030-(CH2) r -NH-C (= 0) -0- K005 J063 T134 1031-( CH2) 2- • NH-C (= 0) -0- K005 J063 T143 1032-(CH2) 2 · -NH-C (= 0) -0- K005 J063 T152 1033-(CH2) 2. -NH-C (= 0) -0- K005 J063 T161 1034-(CH2) 2- -NH-C (= 0) -0- K005 J063 T170 1035-(CH2) 2- -NH-C (= 0) -0- K005 J063 T179 1036 • (ch2) 2 · -NH * C (= 0) -0 · K005 J081 T009 1037-(ch2) 2 · .NH-C (= 0) -0- K005 J081 T018 1038-(CH2) 2- -NH-C (= 0) -0- K005 J081 T027 1039-(CH2) 2 · -NH-C (= 0) -0- K005 J081 T036 1040-(CH2) 2- -NH-C (= 0) -0- K005 J081 T045 1041-(CH2) 2- -NH-C (= 0) -0- K005 J081 T054 1042-(ch2) 2- • NH-C (= 0) -0- K005 J081 T063 1043-(CH2) 2- • NH-C (= 0) -0- K005 J081 T072 1044-(CH2) 2. -NH-C (= 0) '0- K005 J081 T081 1045-(CH2) 2- • NH-C (= 0) -0- K005 J081 T090 1046-(CH2) 2 · • NH-C (= 0) -0- K005 J081 T099 1047-(CH2) 2. -NH-C (= 0) -0- K005 J081 T108 1048-(CH2) 2- -NH-C (= 0)- 0- K005 J081 T117 1049-(ch2) 2- Κ (= 0) · 0- K005 J081 T126 1050-(CH2) r -NH-C (= 0) -0- K005 J081 T135

-151-(147) Compound number -A1 · • A2 · -g1-a3-a, g2 -a5_r2 -a £ -r3 1051-(ch2) 2 · • NH-C (= 0) -0- K005 J081 T144 1052-(〇η2) 2. -NH-C (= 0) -0- K005 J081 T153 1053 -NH-C (= 0) -0- K005 J081 T162 1054-(CH2) 2- -NH-C (= 0) -0- K005 J081 T171 1055-(ch2) 2. Single key K179 J012 T148 1056-(ch2> 2- Single key K180 J045 T148 1057-(CH2) 2- Single key K239 J045 D 148 1058-(CH2) 3_ K002 J001 T151 1059-(CH2) 3- -C (= 0)-K002 J012 T151 1060-(CH2) 3- -C (= 0)-K003 J001 T151 1061-(CH2) 3- _c (= o) -K003 J012 T151 1062-(CH2) 3- K004 J001 T151 1063-(CH2) 3- -C (= 0)-K004 J012 T151 1064-(CH2) r -C (= 0)-K005 J001 T151 1065-( CH2) 3- -C (= 0)-K005 J012 T151 1066-(CH2) 3- -0 (= 〇)-K007 J001 T152 1067-(CH2) 3- -C (= 0). K007 J012 T152 1068- (CH2) 3- -C (= 0)-K008 J001 T152 1069-(CH2) 3- -C (= 0) K008 J012 T152 ^ 1070-(CH2) 3--0 (: 0)-K009 J001 T152 1071-(CH2) 3- -c (= oy K009 J012 T152 1072-(CH2) 3- ** C (= 0)-K012 J001 T152 1073-(CH2) 3- • c (= o) K012 J012 T152 1074 • (CH2) 3- -C (= 0)-K107 J001 T168 1075-(ch2) 3- -C (= 0) K107 J012 T169 -152- (148) Compound numberA1- -A2- -g1-a3-a4-g2 -As-R2 -a6-r3 1076-( CH2) 3.c (= o) K108 J001 Ding 169 1077 • (CH2) 3- -0 (= 〇)-K108 J012 Ding 169 1078-(CH2) 3- _c (= o) _ K112 J001 T170 1079- (CH2) 3- -C (~ 0)-K112 J012 T169 1080-(CH2) r -c (= o)-K129 J001 T171 1081 • (CH2) 3 ~ -0 (= 0)-K129 J012 T169 1082 • (CH2) 3--c (= o)-K133 J001 T172 1083-(CH2) 3- -0 (= 〇)-K133 J012 T169 1084-(ch2) 3 · -c (= o)-K137 J001 T173 1085 • (ch2> 3 · 'c (o) _ K137 J012 T169 1086-(CH2) 3- -C (= 0) -0 * K001 J001 T148 1087-(CH2) r -0 (= 0) -0- K002 J001 T151 1088-(CH2) 3 ~ -C (= 0) -0- K193 J001 T152 1089-(CH2) 3_ -C (: 〇) -〇- K227 J001 T169 1090-(CH2) 3 · -NH- K185 J045 T151 1091-(CH2) 3- -NH- K185 J045 T169 1092-(CH2) 3- -NH-C (= 0)-K008 J012 T151 1093-(CH2) 3 * -NH-C (= 0)- K008 J012 Ding 169 1094-(ch2) 3_ -NH-C (= 0)-K013 J001 T151 1095-(CH2) 3- -NH-C (= 0)-K013 J001 T169 1096 • (ch2) 3- -NH -C (= 0)-K200 J045 T148 1097 • (CH2) 3_ • ΝΗ0 (= 0)-K200 J045 T15 2 1098 • (ch2) 3- -NH-C (= 0) -NH- K003 J012 T148 1099-(CH2) 3 · -NH-C (= 0) -NH · K003 J012 T152 1100-(CH2) 3 · -NH-C (= 0) -0- K005 J001 Ding148-153- 200526665 (149) Compound No.-A1- -A2- -g1-a3-a4-g2 • As-R2 • A, R3 1101-(CH2 ) 3- -NH-C (= 0) -0- K005 J001 T152 1102 -ch2- -C (= 0)-K107 J001 T148 1103 -CH2 · -C (= 0) · K107 J012 T148 1104 ~ CH2 ~- 〇 (= 〇)-K107 J018 T148 1105 -C (= 0) &gt; K108 J001 T129 1106 • CH ^--C (= 0)-K108 J001 T148 1107 -CH2- -C (= 0)-K108 J001 T151 1108 -CH2 · -0 (-0)-K108 J001 T152 1109 -c (= o) · K108 J001 T164 1110 -CH2- -C (= 0)-K108 J001 T170 1111 • ch2 · -C (= 0)- K108 J001 T171 1112 • ch2 · -C (= 0) · K108 J012 T148 1113 -CH2 · -c (= o)-K108 J022 T148 1114 -CH2- • c (= o)-K112 J001 T148 1115 -CHr -C (= 0)-K112 J012 T148 1116 -CH2- -c (= o)-K129 J001 T148 1117 • CHr -C (= 0)-K129 J012 T148 1118 • CH2 * -C (= 0)-K129 J014 T148 1119 -ch2- -C (= 0). K133 J001 T148 1120 -CH2 &quot; -C (= 0)-K133 J008 T148 1121 -CH2- -0 (= O)-K133 J012 T148 1122 -ch2 · -c (= o)-K137 J001 T129 1123 • CHr ~ C (= 0) · K137 J001 T148 1124 -ch2- 'c (= o) _ K137 J001 T151 1125 -ch2 · -C (= 0)-K137 J001 T152- 154- (150) Compound number -A1- • A2- -G1.A3-Aa-G2 -AS.R2 -A, R3 1126 -CH2- -C (= 0)-K137 J001 T164 1127 -ch2--c ( = o)-K137 J001 T170 1128 -ch2 · -c (= o)-K137 J001 T172 1129 -CH2- -c (= o)-K137 J009 T148 1130 -CH2- ~ C (= 0)-K137 J012 T148 1131 -CHr -c (= o)-K237 J001 T148 1132 -CH2- • C (= 0) -MH- K001 J001 T148 1133 -ch2- -G (= 0) -NH- K002 J001 T148 1134 • ch2- -C (= 0) -NH- K002 J012 T148 1135 -ch2- -C (= 0) -NH- K002 J063 T148 1136 -CH2- -C (= 0) -NHK003 J001 T148 1137 -CH》-• C ( = 0) -NH- K003 J012 T148 1138 -CH2- -C (= 0) -NH- K003 J065 T148 1139 -ch2- -C (= 0) -NH- K004 J001 T148 1140 -CH2 · -C (= 0 ) -NHK004 J012 T148 1141 -CH2- -C (= 0〉 -MH- K004 J07D T148 1142 -CH2- -C (= 0) -NH- K005 J001 T148 1143 -CH2 · -C (= 0)- NHK005 J012 T148 1144 -ch2- -C (= 0) -NH- K005 J075 T148 1145 -CHr K007 J001 T129 1146 -CH2 · -C (= 0) -NH- K007 J001 T148 1147 -ch2- -C ( = 0) -NH- K007 J001 T151 1148 -CHj- -C (= 0) -NH- K007 J001 T152 1149 • CH2- -C (= 0) -NHK007 J001 T164 1150 -CHr • C (= 0) -NH- K007 J001 T169 -155- 200526665 (151) Compound number -A1- -A2 · -g1-a3-a4-g2 -a6-r2 -Ae-R3 1151 -ch2- -C (= 0) -NH- K007 J001 T170 1152 -CH2 * -C (= 0) -NH- K007 J012 T148 1153 -CH2- -C (= 0) -NH_ K007 J081 T148 1154 -CH2- -C (= 0) -NH- K008 J001 T148 1155 -ch2 · -C (= 0) -NH ^ K008 J012 T148 1156 -ch2- -C (= 0) -NH- K008 J085 T148 1157 -GH2 · -C (= 0) -NH- K009 J001 T148 1158 * ~ CH2 ~ -C (= 0) -NH- K009 J012 T148 1159 • CH2- -C (= 0) -NH · K009 J043 T148 1160 -CH2 · -C (= 0) -NH- K012 J001 T129 1161 -ch2 -K012 J001 T148 1162 • CH2 · -C (= 0) -NH- K012 J001 T151 1163 -CH2- -C (= 0) -NH- K012 J001 T152 1164 -ch2- -C (= 0) -NH- K012 J001 T164 1165 -CH2- -C (= 0) -NH- K012 J001 T170 1166 -CH2 · -C (= 0) -NH- K012 J012 T148 1167 -CH2 · -C (= 0) -NH- K012 J045 T148 1168 -CH2--C (= 0) -NH- K218 J001 T148 1169 -CH2 · -c (= o) _o- K001 J001 T148 1170 -CH2 · -0 (= 0) -0- K002 J001 T148 1171 -CH2 • C (= 0) -0- K002 J001 T151 1172 • CH2 · -0 (= 0) -0 · K193 J001 T152 1173 -ch2- -0 (= 0). 〇 · K227 J001 T169 11.74 Single key Single key K001 J001 T148 1 * 175 Single Key 'single key K001 J002 T148 -156- 200526665 (152) compound number -A1 · -A2 · -g, a3-a4-g2 -a5-r2 _a6-r3 1176 single key single key K197 J001 T005 1177 single key single key K197 J001 T148 1178 Single key single key K197. J012 T148 1179 Single key single key K223 J001 T148 1180 Single key single key K223 J002 T148 1181-(CH2) 2- -NH- K078 J001 T148 1182-(CH2) 2- -NH -K078 J045 T148 1183-(CH2) 2- -NH- K078 J045 T170 1184-(CH2〉 2- -NH- K182 J001 T148 1185-(CH2) 2. -ΜΗ- K372 J045 T148 1186-(CH2) 2. ΝΗ- K392 J045 T170 1187-(ch2) 2- -NH-C (= 0)-K003 J044 T170 1188-(CH2) 2- -NH-C (= 0)-K004 J007 T148 1189-(CH2) 2 --NH-C (= 0)-K004 J010 T148 1190-(CH2) 2--NH-C (= 0)-K004 J013 T148 1191-(CH2) 2- -NH-C (= 0)-K004 J014 T148 1192-(CH2) 2- -NH-C (= 0) K004 J044 T148 1193-(CH2) 2- -NH-C (= 0)-K004 J044 T170 1194-(CH2) 2- -NH-C (= 0)-K006 J007 T148 1195 _ (CH2> 2- -NH-C ( = 0) K006 J010 T148 1196-(CH2) 2- -NH-C (= 0)-K006 J013 T148 1197-(CH2) 2- -NH-C (= 0) K007 J007 T148 1198-(ch2) 2 · -NH-C (= 0)-K007 J010 T148 1199-(CH2) 2- -NH-C (= 0)-K007 J013 T148 1200-(ch2) 2 · -NH-C (= 0)-K007 J014 T148 -157- 200526665 (153) Compound No.-A1- -A2- -G1-A, A4-G2 • As-R2 -A6.R3 1201 • (ch2) 2_ -NH-C (= 0)-K007 J039 T170 1202-(ch2) 2_ • NH-C (= 0)-K007 J044 T148 1203-(CH2) 2- -NH-C (= 0)-K007 J044 T169 1204-(CH2) 2- -NH-C ( = 0) ~ K007 J044 T170 1205-(CH2) 2. -NH-C (= 0). K007 J045 Ding 151 1206-(CH2) 2- -NH-C (= 0)-K007 J045 T170 1207-(CH2 ) 2- -NH-C (= 0)-K008 J007 T148 1208-(CH2) 2- -NH-C (= 0)-K008 J010 T148 1209-(CH2) 2--NH-C (= 0)- K008 J013 T148 1210-(CH2) 2- -NH-C (= 0). K008 J014 T148 1211-(CH2) 2- -NH-C (= 0)-K008 J039 T170 1212-(CH2) 2- -NH -C (= 0)-K008 J044 T148 1213-(CH2) 2- -NH-C (= 0). K008 J044 T169 1214-(CH2) 2- -NH-C (= 0). K008 J044 T170 1215- (CH2) 2. -NH-C (= 0)-K008 J045 T151 1216-(CH2) 2- -NH-C (= 0)-K008 J045 T169 1217-(CH 士, -NH-C (= 0) -K 008 J045 T170 1218-(CH2) 2. -NH-C (= 0)-K009 J007 T148 1219-(CH2) 2 '-NH-C (= 0)-K009 J010 T148 1220, (ch2) 2_ -NH- C (= 0)-K009 J013 T148 1221 • (CH2) 2- -NH-C (= 0)-K009 J014 T148 1222-(ch2) 2. -NH-C (= 0)-K009 J037 T170 1223-( CH2) 2- -NH-C (= 0) K009 J039 T170 1224-(CH2) 2 · -NH-C (= 0)-K009 J043 T170 1225-(CH2) 2- -NH-C (= 0) K009 J044 T148 -158- 200526665 (154) Compound No.A1- -A2- -G1-A3-A4 ^ G2 -A, R2 -a6-r3 1226-(CH2) 2- -NH-C (= 0) -K009 J044 T170 1227-(CH2) 2 · -NH-C (= 0)-K009 J045 T152 1228-(CH2) 2- -NH-C (= 0)-K009 J045 Ding 170 1229-(CH2) r- NH-C (= 0)-K009 J047 T170 1230-(ch2) 2- -NH-C (= 0)-K009 J145 T148 1231-(CH2) 2_ -NH-C (= 0)-K009 J147 T148 1232- (ch2) 2- -NH-C (= 0)-K010 J012 T148 1233 • (CH2) 2- -NH-C (= 0)-K010 J012 T164 1234-(ch2) 2. -NH-C (= 0 )-K010 J013 T148 1235-(CHa) 2 · -NH-C (= 0) ^ K010 J013 T170 1236-(CH2) 2- • NH-C (= 0)-K010 J045 T148 1237-(ch2) 2- -NH-C (= 0)-K010 J045 T170 1238-(CH2) 2- -NH-C (= 0)-K010 J045 T178 1239-(ch2) 2- • NH-C (= 0)-K010 J045 T179 1240-(CH2) 2 · -NH-C (= 0)-K011 J044 T170 1241 _ (ch2) 2 · -NH-C (= 0) &gt; K023 J045 T170 1242-(ch2) 2 · -NH -C (= 0)-K033 J045 T170 1243 • (CH2) r -NH-C (= 0)-K104 J045 T170 1244-(CH2) 2- -NH-C (= 0)-K198 J007 T148 1245 • ( CH2) 2 · -NH-C (= 0)-K198 J010 T148 1246-(ch2) 2- -MH-C (= 0)-K198 J013 T148 1247-(CH2) 2- -NH-C (= 0) -K198 J014 Ding 148 1248-(CH2) r • C (= 0)-K198 J039 T170 1249 • (CH2) 2- -NH-C (= 0)-K198 J044 T170 1250-(CH2) 2- -C ( = 0)-K198 J045 T170 • 159- 200526665 (155) Compound number-A1- -A, -g1-a3-a4-g2 -a5_r2 • a6-r3 1251 _ (CH2) 2 · -NH-C (= 0 )-K199 J007 T148 1252-(CH2) 2 ^ -NH-C (= 0)-K199 J010 T148 1253 ， (CH2) 2- -NH-C (= 0)-K199 J013 T148 1254-(CH2〉 2- -NH-C (= 0)-K199 J014 T148 1255-(CH2) 2- -NH-C (= 0)-K199 J039 T170 1256-(ch2) 2- -NH-C (= 0). K199 J044 T170 1257-(CH2) 2- -NH-C (= 0)-K199 J045 T170 1258-(GH2) 2- -NH-C (= 0)-K200 J001 T170 1259-(CH2) 2- -NH-C ( = 0) _ K200 J002 T170 1260-(CH2) 2- -NH-C (= 0)-K200 J007 T148 1261-(ch2) 2- -NH-C (= 0)-K200 J00 7 T170 1262-(ch2) 2- -NH-C (= 0)-K200 J008 T170 1263-(CH2) 2- -NH-C (-O)-K200 J009 T164 1264 _ (ch2) 2_ -NH-C (= 0)-K200 J009 T170 1265-(ch2) 2- -NH-C (= 0)-K200 J010 T148 1266-(CH2) 2- • NH-C (= 0)-K200 J010 T170 1267-(CH2 ) 2. -NH-C (= 0)-K200 J011 T148 1268-(CH2) 2- -NH-C (= 0)-K200 J011 T164 1269-(ch2) 2 · -NH-C (= 0)- K200 J011 T170 1270-(CH2) 2_ -NH-C (= 0)-K200 J012 T164 1271-(CH2) r-NH-C (= 0)-K200 J012 T170 1272 • (CH2) 2 · -NH-C (= 0). K200 J013 T148 1273-(CH2) 2. -NH-C (= 0)-K200 J013 T170 1274-(ch2) 2- -NH-C (= 0). K200 J014 T148 1275 ~ (CH2 ) 2- -NH-C (= 0)-K200 J037 T148

-160- 200526665 (156) Compound number -A1- -A2- -G, A3-A4-G2 • A, R2 -a6-r3 1276-(CH2) 2_ -NH-C (= 0) K200 J037 T169 1277 • (ch2) 2- -NH-C (= 0) K200 J037 T170 1278-(CH2) r -NH-C (= 0)-K200 J038 T170 1279-(ch2) 2- -NH-C (= 0 )-K200 J039 T148 1280-(CH2) 2 · -NH-C (= 0) · K200 J039 T164 1281 • (ch2) 2- -NH-C (= 0) · K200 J039 T170 1282-(CH2) 2- _NH-C (= 0)-K200 J043 T148 1283-(CH2) 2- -NH-C (= 0)-K200 J043 T169 1284-(CH2) 2- -NH-C (= 0) K200 J043 T170 1285 -(CH2) 2- -NH-C (= 0)-K200 J044 T148 1286-(CH2) 2 · -NH-C (= 0)-K200 J044 T170 1287-(CH2) 2- -NH-C (= 0)-K200 J045 T164 1288-(CH2) 2- -NH-C (= 0). K200 J045 T170 1289-(ch2) 2 · -NH-C (= 0)-K200 J045 D 171 1290-(CH2) 2- -NH-C (= 0)-K200 J045 T177 1291-(CH2) 2- -NH-C (= 0)-K200 J045 T178 1292-(CH2) 2- -NH-C (= 0)-K200 J045 T179 1293-(CH2) 2- -NH-C (= 0)-K200 J045 T180 1294-(ch2〉 2 · -NH-C (= 0〉-K200 J047 T148 1295-(CH2) 2- -NH- C (= 0)-K200 J047 T169 1296-(CH2) 2- -NH-C (= 0)-K200 J047 T170 1297-(CH2〉 2- -NH-C (= 0)-K200 J079 T14 8 1298-(ch2) 2- -NH-C (= 0)-K200 J079 Ding 169 1299-(CH2) 2- -NH-C (= 0)-K200 J079 T170 1300 • (ch2) 2- -NH- C (= 0)-K200 J080 T148 • 161-(157) Compound number -A1- -A2- -G, A3-A4-G2 -A, R2 • A, R3 1301-(CH2) 2- -NH-C (= OJ- K200 J080 T169 1302-(CH2) 2_ -NH-C (= 0)-K200 J080 T170 1303-(CH2) 2, -NH-C (= 0)-K200 J081 T148 1304-(CH2) 2 --NH-C (= 0) K200 J081 Ding 164 1305-(ch2) 2. -NH-C (= 0)-K200 J081 T170 1306-(CH2) 2- -NH-C (= 0)-K200 J082 T148 1307-(CH2) 2- .NH-C (= 0)-K200 J082 T169 1308-(CH2) 2_ -NH-C (= 0)-K200 J082 T170 1309-(CH2) 2- • NH-C (= 0 Bu K200 J090 T148 1310 • (CH2) 2 · -NH-C (= 0) · K200 J090 T169 1311-(ch2> 2- -NH-C (= 0) ^ K200 J090 T170 1312-(CH2) 2- -NH-C (= 0)-K200 J092 T148 1313-(CH2) 2 · -NH-C (= 0)-K200 J092 T164 1314-(CH2> 2- -NH-C (= 0)-K200 J092 T170 1315-(CH2) 2- -NH-C (= 0)-K200 J093 T148 1316-(CH2) 2_ -NH-C (= 0)-K200 J103 T148 1317 • NH-C (= 0)-K200 J103 T164 1318-(CH2) 2- -NH-C (= 0)-K200 J103 T170 1319-(ch2) 2. -NH-C (= 0)-K200 J104 T148 1 320-(CH2) 2 · -NH-C (= 0)-K200 J104 T164 1321 • (ch2) 2- -NH-C (= 0). K200 J104 T170 1322-(CH2) 2- -NH-C ( = 0)-K200 J105 T148 1323-(CH2) r -NH-C (= 0)-K200 J105 T164 1324-(CH2) 2- -NH-C (= 0)-K200 J105 T169 1325-(CH2) 2 --NH-C (= 0)-K200 J106 T148 -162 (158) Compound No.A1- -A2- -g, a3-a4-g2 -a5-r2 -A, R3 1326-(ch2) 2-- NH-C (= 0)-K200 J106 T164 1327-(ch2) 2- -NH-C (= 0)-K200 J106 T170 1328-(CH2) 2 ~ -NH-C (= 0)-K200 J107 T148 1329 -(CH2) 2 &gt; -NH-C (= 0) K200 J107 T164 1330 _ (ch2) 2- -NH-C (= 0)-K200 J107 T170 1331-(ch2) 2 · -NH-C (= 0)-K200 J109 T170 1332-(ch2) 2- -NH-C (= 0)-K200 J118 T170 1333 -NH-C (= 0) K200 J138 T170. 1334-(CH2) 2- -NH-C (= 0)-K200 J139 T170 1335-(CH2) 2 * -NH-C (= 0)-K200 J144 T148 1336-(ch2) 2. -NH-C (= 0)-K200 J144 T169 1337-(CH : 2) 2- -NH-C (= 0) · K200 J144 T170 1338-(CH2) 2. -NH-C (= 0 Bu K200 J145 T170 1339-(CH2) 2 · -NH-C (= 0) -K200 J146 T148 1340-(ch2) 2. -NH-C (= 0)-K200 J146 T164 1341-(CH2) 2- -NH-C (-O)-K200 J105 T170 1342-(ch2) 2-- NH-C (= 0 )-K200 J147 T148 1343 • (CH2) 2- -NH-C (= 0)-K200 J147 T170 1344-(ch2) 2- -NH-C (= 0)-K200 J148 T148 1345 ~ (CH2) 2- -NH-C (= 0)-K200 J149 T148 1346-(CH2) 2- -NH-C (= 0)-K200 J149 T170 1347-(CH2) 2- -NH-C (= 0) _ K200 J150 T148 1348-(CH2) 2- -NH-C (= 0)-K200 J150 T170 1349-(CH2) r -NH-C (= 0)-K200 J151 T148 1350-(CH2) 2- -NH-C (= 0)-K200 J151 T170 -163- (159) Compound number -A1- -A2- -g1_a3-a4-g2 -a5-r2 -a6-r3 1351-(CH2) 2- -NH-C (=: 0) -K200 J152 T148 1352-(CH2) 2- -NH-C (= 0)-K200 J153 T148 1353-(CH2) 2 · -NH-C (= 0)-K200 J154 T148 1354-(CH2) 2-- NH-C (= 0)-K200 J155 T148 1355-(CH2) 2, -NH-C (= 0)-K200 J156 T148 1356-(CH2) 2- -NH-C (= 0)-K200 J157 T148 1357 _ (ch2) 2- -NH-C (= 0)-K200 J158 T148 1358-(CH2) 2- -NH-C (= 0)-K200 J158 T170 1359-(ch2) 2- -NH-C (= 0)-K200 J159 T148 1360-(CH2) 2- &gt; NH-C (= 0) K200 J159 T170 1361-(CH2) 2- -NH-C (= 0)-K201 J007 T148 1362-(CH2) 2 «-NH-C (= 0)-K201 J008 T148 1363 &quot; (CH2) 2- -NH-C (= 0)-K201 J010 T148 1364-(CH2) 2- -NH-C (= 0) _ K201 J012 T148 1365 • (ch2) 2_ -NH-C (= 0)-K201 J013 T148 1366-(CH2) 2 · -NH-C (= 0) · K201 J014 Ding 148 1367-(CH2) r -NH-C (= 0) K201 J037 T170 1368-(CH2) 2- -NH-C (= 0) ^ K201 J039 T170 1369 _ (ch2) 2 ': nh-c (= o)-K201 J043 T170 1370-(CH2) 2 --NH-C (= 0)-K201 J044 T148 1371-(CH2) 2 ~ -NH-C (= 0)-K201 J044 T170 1372-(CH2) 2- -NH-C (= 0)-K201 J045 T148 1373-(ch2) 2- -NH-C (= 0)-K201 J045 T152 1374-(CH2) 2- -NH-C (= 0)-K201 J045 T170 1375-(CH2) 2_ -NH-C ( = 0) K201 J047 Ding 170 -164- 200526665 (160) Compound number -A1- -A2- -G, A3-A4-G2 -As-R2 -a6-r3 1376-(CH2) 2- -NH-C (= 0)-K201 J145 T148 1377-(ch2) 2- -NH-C (= 0)-K201 J147 T148 1378 • (CH2) r -NH-C (= 0). K202 J007 T148 1379-(ch2) 2_ -NH-C (= 0) «K202 J008 Ding 148 1380 _ (CH2) 2_ -NH-C (= 0)-K202 J010 T148 1381-(CH2) r -NH-C (= 0)-K202 J012 T148 1382-(CH2) 2 * -NH-C (= 0)-K202 J013 T148 1383-(CH2) 2_ -NH_C (= 0)-K202 J014 Ding 148 1384-(CH2) 2- -NH-C (= 0 )-K202 J039 Ding 170 1385-(ch2) 2- -NH-C (= 0)-K202 J044 T148 1386-(CH2) 2. -NH-C (= 0> K202 J044 T164 1387-(CH2) 2- -NH-C (= 0)-K202 J044 T170 1388-(ch2) 2- -NH-C (= 0)-K202 J045 T148 1389-(CH2) 2- _NH-C (= 0)-K202 J045 T164 1390-(CH2) 2 · -NH-C (= 0)-K203 J007 T148 1391-(CH2) 2- -NH-C (= 0)-K203 J010 T148 1392-(CH2) 2 --NH-C (= 0)-K203 J013 T148 1393-(ch2) 2- -NH-C (= 0)-K203 J014 T148 1394-(CH2) 2- -NH-C (= 0)-K203 J039 Ding 170 1395-(CH2) 2- -NH-C (= 〇)-K203 J044 T148 1396-(CH2) 2 · -NH-C (= 0) · K203 J044 T164 1397-(ch2) 2- -NH- C (= 0) _ K203 J044 T170 1398-(CH2) 2 · -NH-C (= 0)-K203 J045 Ding 164 1399-(CH2) 2 ~ -NH-C (= 0)-K203 J045 T170 1400- (ch2) 2- -NH-C (= 0)-K204 J007 T148 -165- 200526665 (161) Compound number -A1- -A2- -g1-a3-a ~ g2 -a5-r2 -a6-r3 1401- (CH2) 2- -NH-C (= 0)-K204 J008 T148 1402-(CH2): r -NH-C (= 0)-K204 J009 T170 1403-(CH2) 2 · -NH-C (= 0 )-K204 J010 T148 1404-(CH2) 2, -NH-C (= 0) · K204 J011 T170 1405-(〇Ha) r -NH-C (= 0)-K204 J012 T148 1406-(CH2) 2 · -NH-C (= 0)-K204 J013 T148 1407-(ch2) 2- -NH-C (= 0)-K204 J037 T170 1408-(ch2) 2- -NH-C (= 0) K204. J039 T170 1409-(CH2) 2- -NH-C (= 0)-K204 J043 T170 1410-(CH2) 2- -NH_C (= 0) K204 J044 T148 1411-(CH2) r -NH-C (= 0) -K204 J044 T169 1412-(CH2) 2- • NH-C (= 0)-K204 J044 T170 1413-(ch2) 2- -NH-C (= 0)-K204 J045 T148 1414-(CH2) 2.-- NH-C (= 0)-K204 J045 T169 1415 Jens -c (= o)-K204 J045 T170 1416-(CH2) 2- -NH-C (= 0)-K204 J047 T170 1417-(CH2) 2 --NH-C (= 0)-K204 J079 T170 1418-(CH2) r • NH-C (= 0 Bu K204 J145 T148 1419 ~ (CH2) 2- -NH-C (= 0) K204 J147 T148 1420 -(CH2) 2_ -NH-C (= 0)-K205 J007 T148 1421-(CH2) 2 * -NH-C (= 0)-K205 J008 T148 1422-(ch2) 2. • NH-C (= 0 )-K205 J010 T148 1423-(CH2) 2- -NH-C (= 0)-K205 J012 T148 1424-(ch2v -NH-C (= 0)-K205 J013 T148 1425-(ch2) 2. -NH- C (= 0)-K205 J014 T148 -166- 200526665 (162) Compound No.-A1- -A2- • g, a3-a4-g2 -a5.r2 -A, R3 1426-(CH2) 2- -NH- C (= 0)-K205 J044 T170 1427-(CH2>; r -NH-C (= 0)-K205 J045 T170 1428-(CH2) 2 · • NH-C (= 0) · K206 J039 T170 1429-( CH2) 2 ~ -NH-C (= 0)-K206 J044 T170 1430-(ch2) 2- -NH-C (= 0)-K206 J045 T170 1431- (CH2) 2- -NH-C (= 0)-K207 J044 T170 1432-(CH2) 2- -NH-C (= 0) _ K208 J007 T148 1433-(Chi2) 2- -NH-C (= 0 )-K208 J009 T170 1434-(CH2) 2 ~ -NH-C (= 0)-K208 J010 T148 1435 -c -NH-C (= 0)-K208 J011 T170 1436-(CH2) 2- -NH-C (= 〇V K208 J013 T148 1437-(CH2) 2- -NH «C (= 0)-K208 J014 T148 1438-(CH2) 2- -NH-C (= 0)-K208 J037 T170 1439-(CH2) 2--NH-C (= 0)-K208 J039 T170 1440-(CH2) 2. -NH-C (= 0)-K208 J043 T170 • 1441 • (CH2) 2 · -NH-C (= 0)- K208 J044 T148 1442-(CH2) 2. -NH-C (= 0)-K208 J044 T169 1443-(CH2) 2- -NH-C (= 0)-K208 J044 T170 1444-(CH2) 2- -NH ^ C (= 0)-K208 J045 T169 1445-(CH2) 2- -NH-C (= 0)-K208 J045 T170 1446-(CH2) 2- -NH-C (= 0)-K208 J047 T170 1447- (CH2) 2- -NH-C (= 0)-K208 J079 T170 1448-(CH2) 2- -NH-C (= 0)-K208 J145 T148 1449-(CH2) r -NH-C (= 0) -K208 J147 T148 1450 • (CH2) 2 · -NH-C (= 0 Bu K209 J007 T148 -167- (163) Compound number • A1- -A2- -g, a, a4-g2 • A, R2 -As -R3 1451 • (CH2) r -NH-C (= 0)-K209 J010 T148 1452-(ch2) 2- -NH-C (= 0)-K209 J013 T148 1453-(CH2) 2- -NH-C (= 0 )-K209 J014 T148 1454 • (CH2) 2- -NH-C (= 0)-K209 J044 T170 1455-(CH2) 2- -NH-C (= 0)-K210 J007 T148 1456-(ch2) 2- -NH-C (= 0)-K210 J010 T148 1457-(CH2) 2- -NH-C (= 0)-K210 J013 T148 1458-(ch2) 2- -NH-C (= 0)-K210 J014 T148 1459-(CH2) 2- -NH-C (= 0)-K210 J044 T170 1460 • (CH2) 2. -NH-C (= 0)-K213 J007 T148 1461 • (ch2) 2- -NH-C ( = 0)-K213 J008 T148 1462-(CH2) 2- -NH-C (= 0)-K213 J010 T148 1463-(CH2) 2- -NH-C (= 0)-K213 J012 T148 1464-(CH2) 2- -NH-C (= 0)-K213 J013 T148 1465-(ch2) 2- -NH-C (= 0)-K213 J014 T148 1466-(ch2) 2- -NH-C (= 0)-K213 J044 T170 1467-(CH2) 2. -NH-C (= 0)-K214 J007 T148 1468-(CH2) 2- -NH-C (= 0)-K214 J008 T148 1469-(CH2) r -NH-C (= 0). K214 J010 T148 1470-(CH2) 2, * NH-C (= 0)-K214 J012 T148 1471 • (CH2) 2- -NH-C (= 0). K214 J013 T148 1472 • (CH2 ) r -NH-C (= 0)-K214 J014 T148 1473-(CH2) 2- -NH-C (= 0)-K214 J044 T170 1474-(ch2) 2- -NH-C (= 0)-K215 J007 T148 1475-(CH2) r -NH-C (= 0)-K215 J010 T148 -168- 200526665 (164) Compound number -A1- -A2- -G, A, A, G2 -a5-r2 -a6-r3 1476-(CH2) r -NH-C (= 0)-K215 J013 T148 1477 -NH-C (= 0)-K215 J014 T148 1478-(ch2) 2- -NH-C (= 0) -K215 J044 T170 1479-(CH2) 2_ -NH-C (= 0)-K216 J007 T148 1480-(ch2> 2- -NH-C (= 0)-K216 J008 T148 1481 • (ch2) 2 · -NH -C (= 0)-K216 J010 T148 1482-(ch2) 2- -NH-C (= 0)-K216 J012 T148 1483-(CH2) 2- -NH-C (= 0)-K216 J013 T148 1484- (CH2) 2- -NH-C (= 0)-K216 J014 T148 1485-(ch2) 2- -NH-C (= 0)-K216 J044 T170 1486-(CH2) 2- -NH-C (= 0 )-K216 J045 T170 1487-(CH2) 2- -NH-C (= 0)-K217 J007 T148 1488 -NH-C (= 0) K217 J008 T148 1489-(CH2) 2 &quot; -NH-C (= 0)-K217 J010 T148 1490-(CH2) 2 ~ -NH-C (= 0)-K217 J012 T148 1491-(CH2) 2- -NH-C (= 0)-K217 J013 T148 1492-(ch2) 2 --NH-C (= 0)-K217 J014 T148 1493-(CH2) 2- -NH-C (= 0)-K217 J044 T170 1494-(ch2) 2_ -NH-C (= 0)-K217 J045 T170 1495-(CH2) 2. -NH-C (= 0)-K218 J007 T148 1496 _ (ch2) 2. -NH-C (= 0)-K218 J008 T148 1497 r-(CH2) 2- -NH-C (= 0)-K218 J010 T148 1498-(ch2) 2, -NH-C (= 0)-K218 J012 T148 1499-(CH2) 2_ -NH-C (= 0)-K218 J012 T164 1500-(C H2) 2- -NH-C (= 0)-K218 J013 T148 -169- (165) Compound No.-A1- -A, -G, A3-A4-G2 -As-R2 -a8-r3 1501-(CH2 〉 2_ • NH-C (= 0 Bu K218 J013 T170 1502-(CH2) 2_ -NH-C (= 0)-K218 J014 T148 1503-(CH2) 2- -NH-C (= 0)-K218 J044 T170 1504-(CH2) 2- C (= 0) _ K218 J045 T170 1505-(ch2) 2- -NH-C (= 0)-K218 J045 T178 1506-(ch2) 2- -NH-C (= 0) -K218 J045 T179 1507-(CH2) 2. -NH-C (= 0)-K222 J007 T148 1508-(CH2) 2_ -NH_C (= 0)-K222 J010 T148 1509 • (ch2) 2- -NH-C (= 0)-K222 J013 T148 1510-(CH2) 2- -NH-C (= 0)-K222 J014 T148 1511-(ch2) 2- -NH-C (= 0)-K240 J045 T148 1512 &quot; ch2 ) 2- -NH-C (= 0)-K242 J045 T169 1513-(CH2) 2_ • NH_C (= 0) _ K242 J045 T170 1514 • (ch2) 2- -NH-C (= 0)-K243 J045 T170 1515-(CH2) 2- -NH-C (= 0)-K244 J045 T169 1516-(CH2) 2- -NH-C (= 0)-K244 J045 Ding 170 1517 • (ch2) 2- -NH-C (^ O)-K245 J045 T170 1518 _ (CH2) 2, -NH-C (= 0)-K246 J045 T170 1519-(ch2) 2 · -NH-C (= 0)-K247 J012 T148 1520-(CH2 ) 2- -NH-C (= 0)-K247 J045 T148 1521 • (ch2) 2- -NH-C (= 0)-K247 J045 T170 1522-(ch2) 2- -NH -C (= 0)-K248 J045 T148 1523 _ (CH2) 2- -NH-C (= 0) K248 J045 T170 1524-(CH2) r -NH-C (= 0)-K249 J007 T148 1525-( CH2) 2_ -NH-C (= 0)-K249 J008 T148 -170- 200526665 (166) Compound number -A1--A2- -g1-a3-a4-g2 -A, R2 ^ a6-r3 1526-(ch2 ) 2--NH-C (= 0)-K249 J010 T148 1527-(ch2) 2- -NH-C (= 0)-K249 J013 T148 1528-(CH2) 2- -NH-C (= 0)- K249 J014 T148 1529-(CH2) 2_ -NH-C (= 0) K249 J045 T170 1530-(CH2) 2--NH-C (= 0)-K250 J045 T148 1531 _ (ch2) 2- -NH- C (= 0)-K250 J045 T170 1532-(CH2) 2- -NH-C (= 0)-K251 J045 T170 1533-(ch2) 2- -NH-C (= 0)-K252 J045 D 148 1534- (ch2) 2 · -NH-C (= 0)-K252 J045 T170 1535-(ch2) 2- -NH-C (= 0)-K253 J045 T148 1536-(CH2) 2- -NH-C (= 0 ). K253 J045 T170 1537-(CH2) 2- -NH-C (= 0)-K254 J007 T148 1538-(ch2) 2. -NH-C (= 0)-K254 J008 T148 1539-(CH2) 2 · -NH-C (= 0)-K254 J010 T148 1540-(CH2) 2- -NH-C (= 0 Bu K254 J012 T148 1541 ㈣ (ch2) 2- -NH-C (= 0)-K254 J013 T148 1542 -(CH2) 2- -NH-C (= 0)-K254 J014 T148 1543-(CH2) 2- • NH-C (= 0)-K254 J044 T170 1544-(CH2) 2 · -NH-C (= 0 )-K254 J045 T169 1545-(CH2) 2 · -NH-C (= 0)-K254 J045 T170 1546-(CH2〉 2- -NH-C (= 0)-K255 J012 T148 1547-(CH2) 2. • NH-C (= 0)-K255 J045 T169 1548-(CH2) 2- -NH-C (= 0). K255 J045 T170 1549 • (CH2) 2- -NH-C (= 0)-K256 J012 T148 1550-(CH2) 2- · 〇 (= 〇) · K256 J039 T170 -171-200526665 (167) Compound No.-A1- -A2 · -g, a3-a4-g2 -a5-r2 -a6-r3 1551- (CH2) 2- -NH-C (= 0)-K256 J044 T170 1552 • (CH2) 2- -NH ^ C (= 0)-K256 J045 T169 1553-(CH2) 2- -NH-C (= 0 )-K256 J045 T170 1554-(CH2) r -NH-C (= 0). K257 J012 T148 1555-(CH2) 2- -NH-C (= 0)-K257 J039 T170 1556-(CH2) 2.-- NH-C (= 0)-K257 J044 T170 1557-(CH2) 2. -NH-C (= 0)-K257 J045 T169 1558 、 (CH2) 2_ -NH-C (= 0)-K257 J045 T170 1559- (ch2) 2. -NH-C (= 0)-K258 J012 T148 1560-(CH2) 2- -NH-C (= 0) K258 J045 T169 1561-(CH2) 2- -NH-C (= 0 )-K258 J045 T170 1562-(CH2) 2- -NH-C (= 0)-K259 J012 T148 1563-(CH2) 2- -NH.C (= 0)-K259 J039 T170 1564-(CH2) 2- -NH-C (= 0)-K259 J044 T170 1565-(CH2) 2- -NH-C (= 0)-K259 J045 T169 1566-(CH2) 2 · -NH-C (= 0)-K2 59 J045 T170 1567-(ch2) 2- -NH-C (= 0)-K260 J012 T148 1568-(ch2) 2- -NH.C (= 0)-K260 J045 T169 1569-(CH2> 2- -NH -C (= 0)-K260 J045 T170 1570-(CH2) 2- -NH-C (= 0)-K261 J012 T148 1571-(CH2> 2- Complement-C (= 0)-K261 J045 T169 1572-( ch2) 2- -NH-C (= 0)-K261 J045 T170 1573-(CH: J) 2- -NH-C (= 0)-K262 J007 T148 1574-(CH2) r -NH-C (:. 0) K262 J008 T148 1575 ** (CH2) 2- -NH-C (= 0)-K262 J010 Ding148-172- 200526665 (168) Compound number-A1- -A2- -g1-a3-a4-g2 -a5-r2 -A, R3 1576-(ch2) 2- -NH-C (= 0)-K262 J012 T148 1577-(CH2) 2- -NH-C (= 〇K262 J013 T148 1578-(CH2) 2- -NH-C (= 0)-K262 J014 T148 1579-(CH2) 2- -NH-C (= 0)-K262 J044 T148 1580-(ch2) 2 · -NH-C (= 0)-K262 J044 T170 1581-(CH2) 2- _NH.C (= 0). K262 J044 T178 1582-(CH2) 2 · -NH-C (= 0)-K262 J045 T148 1583-(CH2) 2_ -NH-C ( = 0)-K262 J045 T169 1584 _ (ch2) 2- -NH-C (= 0)-K262 J045 T170 1585-(ch2) 2- -NH-C (= 0)-K262 J045 T178 1586-(CH2) 2_ -NH-C (= 0)-K263 J007 T148 1587-(CH2) 2- -NH-C (= 0)-K263 J008 T148 1588-(CH2) 2- -NH-C (= 0)-K263 J 010 T148 1589 -NH-C (= 0)-K263 J012 T148 1590-(ch2) 2- -NH-C (= 0). K263 J012 T164 1591-(CH2) 2- -NH-C (= 0)- K263 J013 T148 1592 _ (CH2) 2- • NH-C (= 〇)-K263 J013 T170 1593-(CH2) 2 ** -NH-C (= 0)-K263 J014 T148 1594 _ (ch2) 2 ·- NH-C (= 0)-K263 J039 T170 1595-(CH2) 2, ~ NH-0 (=: 0) · K263 J044 T148 1596-(CH2) 2- -NH-C (= 〇) · K263 J044 T170 1597-(CH2) 2- -NH-C (= 0)-K263 J044 T179 1598 ， (CH2) 2 · -NH-C (= 0) · K263 J045 T148 1599-(ch2) 2- -NH-C ( = 0)-K263 J045 T169 1600-(CH2) 2- -NH-C (= 0)-K263 J045 T170 -173 · 200526665 (169) Compound No.-A1- -A2 · -G1-A3-A4-G2- a5-r2 -a6-r3 1601-(CH2) 2_ -NH-C (= 0)-K263 J045 T178 1602-(〇H2) r -NH-C (= 0)-K263 J045 T179 1603-(ch2) 2 -• NH-C (= 0)-K264 J012 T148 1604-(CH2) 2- -NH-C (= 0)-K264 J045 T169 1605-(CH2) 2- ~ NH-C (= 0)-K264 J045 T170 1606-(CH2) 2- -NH ~ C (= 0)-K265 J012 T148 1607-(CH2) 2- -NH-C (= 0)-K265 J044 T148 1608-(CH2) 2- -NH-C (= 0)-K265 J044 T180 1609-(ch2) 2- -NH-C (= 0)-K265 J045 T148 1610-(CH; 2) 2 · -NH-C (= 0)-K265 J045 T 169 1611-(CH2) 2- -NH-C (= 0)-K265 J045 T170 1612-(ch2) 2- -NH-C (~ 0)-K265 J045 T180 1613-(CH2) 2- -NH-C (= 0)-K266 J012 T148 1614-(CH2) 2- -NH-C (= 0)-K266 J045 T169 1615-(ch2) 2- -NH-C (= 0)-K266 J045 T170 1616-(CH2 ) 2- -NH-C (= 0)-K267 J012 T148 1617-(CH2) 2- • NH-C (= 0)-K267 J045 T169 1618-(CH2) 2_ -NH-C (= 0)-K267 J045 T170 1619-(CH2) 2- -NH-C (= 0)-K268 J012 T148 1620-(CH2) 2- -NH-C (= 0)-K268 J045 T170 1621-(CH2) 2 · -NH- C (= Q)-K269 J012 T148 1622-(ch2) 2. -NH-C (= 0)-K269 J045. T170 1623-(CH2) 2_ • C (= 0) K210 J012 T148 1624-(CH2) 2_ -NH-C (= 0)-K270 J045 T170 1625 • (CH2) 2_ -NH-C (= 0)-K271 J012 T148 174- (170) Compound No.A1- -A2- -G, A3-A4 -G2 -As-R2 -a6-r3 1626-(CH2) 2- -NH-C (= 0)-K271 J045 T169 1627 • (ch2> 2- -NH-C (= 0). K271 J045 T170 1628- (CH2〉 2- -NH-C (= 0)-K272 J012 Ding 148 1629-(ch2) 2- -NH-C (= 0)-K272 J045 T169 1630-(CH2〉 2- -NH-C (= 0)-K272 J045 T170 1631-(CH2) 2- -NH-C (= 0)-K273 J012 T148 1632-(CH2>: r -NH-C (= 0)-K273 J045 T170 163 3-(CH2) 2 · -NH-C (= 0). K274 J012 T148 1634-(CH2) 2- -NH-C (= 0)-K274 J045 T170 1635-(CH2) 2- -NH-C ( = 0)-K275 J007 T148 1636-(CH2) 2- -NH-C (= 0)-K275 J008 T148 1637-(ch2) 2- -NH-C (= 0)-K275 J010 T148 1638-(CH2) 2- -NH-C (= 0)-K275 J012 T148 1639-(CH2) 2- -NH-C (= 0)-K275 J013 T148 1640-(ch2) 2- -NH-C (= 0)-K275 J014 T148 1641-(CH2) 2- -NH-C (= 0)-K275 J044 T170 1642-(CH2) 2 · -NH-C (= 0)-K275 J045 T169 1643-(ch2) 2- -NH- C (= 0)-K275 J045 T170 1644-(CH2) 2- -NH-C (= 0)-K276 J007 T148 1645-(CH2) 2. -NH-C (= 0)-K276 J008 T148 1646, ( ch2) 2 · NH-C (= 0)-K276 J010 T148 1647-(CH2) 2- -NH-C (= 0) K276 J012 T148 1648-(CH2) r -NH-C (= 0)- K276 J012 T164 1649-(ch2) 2- -NH-C (= 0)-K276 J013 T148 1650 * (CH2) 2- -NH-C (= 0)-K276 J013 T170 -175- (171) Compound number- A1- -A2 · g, a3-a4-g2 • As-R2 -a6-r3 1651-(CH2) 2 ~ -NH-C (= 0)-K276 J014 T148 1652-(CH2) 2- -NH- C (= 0)-K276 J044 T170 1653-(CH2) r -NH-C (= 0)-K276 J045 T169 1654-(ch2) 2 · -NH-C (= 0)-K276 J045 T170 1655-(CH2 ) 2- _NH-C (= 0) _ K276 J045 T178 1656-(CH2) 2- -NH-C (= 0). K276 J045 T179 1657-(ch2) 2- -NH-C (= 0)-K277 J045 T170 1658-(CH2) 2- _NH -C (= 0)-K278 J045 T170 1659 • (ch2) 2- • NH-C (= 0)-K279 J045 T170 1660-(ch2) 2_ -NH-C (= 0)-K280 J012 T148 1661 -NH -C (= 0)-K280 J045 T170 1662-(ch2) 2 · -NH-C (= 0)-K281 J045 T170 1663-(CH2) 2- -NH-C (= 0)-K282 J045 T170 1664- (ch2) 2. -NH-C (= 0)-K283 J045 T170 1665-(CH2) 2- -NH-C (= 0) K284 J045 T170 1666-(ch2) 2.-NH-C (= 0 )-K285 J045 T170 1667 • (CH2) 2_ • NH-C (= 0)-K286 J045 T170 1668-(ch2) 2- -NH-C (= 0)-K287 J045 T170 1669-(CH2) 2_ -NH -C (= 0) · K288 J045 T170 1670 • (CH2) 2_ -NH-C (= 0)-K289 J007 T148 1671-(CH2) 2 · -NH-C (= 0) · K289 J008 T148 1672 • ( ch2) 2 · -NH-C (= 0)-K289 J010 T148 1673-(CH2) 2 · -NH-C (= 0)-K289 J012 T148 1674-(CH2) 2_ · ΝΗ-0 (κΟ)-K289 J013 T148 1675-(CH2) r -NH-C (= 0) K289 J014 T148 -176- (172) Compound number -A1- • A2- -G, A3-A4-G2 -A, R2 1676-(CH2 ) 2 * -NH-C (= 0)-K289 J044 T169 1677-(CH2) r -NH-C (= 0) K289 J044 T170 1 678-(CH2) 2- -NH-C (= 0)-K289 J045 T169 1679-(ch2) 2. -NH-C (= 0)-K289 J045 T170 1680-(ch2) 2 · -NH-C ( = 0)-K290 J045 T170 1681 -NH-C (= 0)-K291 J045 T170 1682-(CH2) 2 · -NH-C (= 0)-K292 J045 T148 1683-(CH2) 2- -NH-C (= 0)-K292 J045 T170 1684-(CH2) 2- -NH-C (= 0)-K293 J007 T148 1685-(CH2) 2- -NH-C (= 0)-K293 J008 T148 1686 _ (CH2 ) 2- -NH-C (= 0)-K293 J010 T148 1687 • (CH2) 2- • NH-C (= 0)-K293 J012 T148 1688-(ch2) 2- -NH-C (= 0)- K293 J013 T148 1689-(CH2) r -NH-C (= 0)-K293 J014 T14B 1690-(CH2) 2. -NH-C (= 0)-K293 J044 T170 1691-(CH2) 2- -NH- C (= 0)-K293 J045 T148 1692-(CH2) 2 · -NH-C (= 0)-K293 J045 T169 1693-(ch2) 2. -NH-C (= 0)-K293 J045 T170 1694-( CH2) 2 · -NH-C (= 0)-K294 J045 T170 1695 _ (CH2) 2 · • NH-C (= 0)-K295 J045 T170 1696-(CH2) 2 · -NH-C (= 0) -K295 / K296 J045 T148 1697-(CH2) r -NH-C (= 0)-K296 J045 T170 1698-(CH2) 2- -NH-C (= 0)-K297 J045 T170 1699 "(CH2) 2 · -NH-C (= 0)-K298 J045 T148 1700 • (CH2) 2_ -NH-C (= 0) · K298 J045 T170 177- 200526665 (173) Compound number • A1 ·- A2- -g1-a3-a4-g2 -a5-r2 -a6-r3 1701-(ch2) 2- -NH-C (= 0)-K299 J045 T170 1702-(CH2) 2- -NH-C (= 0)-K300 J045 T170 1703-(ch2) 2. -NH-C (= 0)-K301 J044 T170 1704-(CH2) 2- -NH-C (= 0) _ K301 J045 T169 1705-(CH2) 2 --NH-C (= 0)-K301 J045 T170 1706-(CH2) 2- • NH-C (= 0)-K302 J012 T148 1707-(CH2) 2- -NH-C (= 0)-K302 J044 T170 1708-(CH2) 2- -NH-C (= 0)-K302 J045 T170 1709-(CH2) r -NH-C (= 0)-K303 J007 T148 1710-(CH2) 2. -NH-C ( = 0 Bu K303 J008 T148 1711-(CH2) 2- -NH-C (= 0)-K303 J010 T148 1712-(CH2) 2- -NH-C (= 0)-K303 J013 T148 1713-(CH2) 2 --NH-C (= 0)-K303 J014 T148 1714 _ (CH2) 2- -NH-C (= 0) _ K303 J044 T170 1715-(CH2) 2- -NH-C (= 0)-K303 J045 T148 1716-(CH2) 2- _NH-C (= 0)-K303 J045 T169 1717-(CH2) 2 · -NH-C (= 0)-K303 J045 T170 1718-(CH2) 2 · NH-C ( = 〇V K304 J012 T148 1719 • (ch2) 2- -NH-C (= 0)-K304 J045 T148 1720 • (CH2> 2- • nh-c (= o)-K304 J045 T170 1721-(CH2) r -NH-C (= 0)-K305 J045 T148 1722-(ch2) 2- -NH-C (= 0) K305 J045 T170 1723 • (ch2) 2- -NH * C (= 0)-K306 J044 T170 1724 _ ( ch2) 2 · -NH-C (= 0)-K306 J045 T170 1725 _ (CH2) 2--NH-C (= 0)-K307 J045 T170 -178- 200526665 (174) Compound No.-A1 · -A2 · -G1-A3-A4-G2 -a5-r2 -A6.R3 1726-(CH2) 2- -NH-C (= OJ- K308 J007 T148 1727-(CH2) 2. -NH-C (= 0) K308 J008 T148 1728 ~ (CH2) 2- -NH-C (= 0)-K308 J010 T148 1729-(CH2) 2- -NH-C (= 0)-K308 J012 T148 1730-(CH2) r -NH- C (= 0)-K308 J013 T148 1731-(ch2) 2- -NH-C (= 0)-K308 J014 T148 1732-(CH2> 2- .NH-C (= 0)-K308 J045 T170 1733-( CH2) 2. -NH-C (= 0 Bu K309 J045 T170 1734-(CH2) 2- -NH-C (= 0)-K310 J045 T170 1735-(ch2) 2- -NH-C (= 0) _ K311 J045 T170 1736-(CH2) 2- -NH-C (= 0)-K312 J012 T148 1737-(CH2) 2- -NH-C (= 0)-K312 J045 T170 1738-(CH2) 2_ -NH- C (= 0) ~ K313 J012 T148 1739-(CH2) 2- -NH-C (= 0)-K313 J045 T148 1740 • (CH2〉 2- -NH ^ C (= 0)-K313 J045 T170 1741-( ch2) 2 · -NH-C (= 0)-K314 J007 T148 1742 _ (CH2) 2 · -NH-C (= 0)-K314 J008 T148 1743-(CH2) 2, -NH-C (= 0) -K314 J010 T148 1744-(ch2) 2. -MH-C (= 0)-K314 J012 T148 1745-(CH2> 2- • NH-C (= 0) K314 J013 T148 1746 • ( CH2) r -NH ~ C (= 0)-K314 J014 T148 1747-(ch2) 2 · -NH-C (= 0)-K314 J044 T170 1748 • (ch2) 2 '-NH-C (= 0)- K314 J045 T148 1749-(CH2) r -NH-C (= 0)-K314 J045 T169 1750-(CH2) 2 · -NH-C (= 0) ^ K314 J045 T170 -179- 200526665 (175) Compound number- A1- • A2- • g1-a3-a4-g2 • As-R2 • A, R3 1751-(CH2) 2, -NH-C (= 0) K315 J045 T148 1752 • (ch2) 2- -NH- C (= 0) K315 J045 T170 1753-(CH2) 2- -NH-C (= 0)-K316 J045 T148 1754 • (ch2) 2- -NH-C (= 0)-K316 J045 T170 1755-( CH2) 2_ -NH-C (= 0)-K317 J012 T148 1756 • (CH2) r * -NH-C (= 0). K317 J045 T170 1757-(CH2) 2 · -NH-C (= 0)- K318 J045 T170 1758-(CH2) r -NH-C (= 0)-K319 J045 T148 1759 _ (CH2) 2- -NH-C (= 0)-K319 J045 T170 1760-(ch2) 2- -NH- C (= 0)-K320 J045 T170 1761-(ch2) 2 · -NH-C (= 0) «K321 J045 T170 1762-(CH2) 2 · -NH-C (= 0)-K322 J045 T170 1763-( CH2) 2_ -NH-C (= 0)-K323 J007 T148 1764-(CH2) 2 · -NH-C (= 0)-K323 J008 T148 1765 • (ch2) 2- -NH-C (= 0)- K323 J010 T148 1766-(CH2) 2. • NH-C (= 0)-K323 J013 T148 1767-(CH2) 2- -NH-C (= 0)-K323 J014 T148 1768-(CH2) 2- -NH-C (= 0)-K323 J045 T169 1769-(CH2) 2- -NH-C (= 0)-K323 J045 T170 1770-(CH2) 2- -NH-C ( = 0)-K326 J045 T170 1771-(ch2) 2. -NH-C (= 0)-K332 J012 T148 1772-(CH2) 2, -NH-C (= 0)-K332 J012 T164 1773-(ch2) 2. -NH-C (= 0)-K332 J013 T148 1774-(ch2) 2- -NH-C (= 0) K332 J013 T170 1775-(CH2) 2- -NH-C (= 0)-K332 J045 T170

-180- 200526665 (176) Compound number -A1- -A2. -G1-a3-a4-g2 -a5-r2 -A $ -R3 1776-(CH2) 2- -NH-C (= 0)-K332 J045 T178 1777-(CH2) 2- -NH-C (= 0)-K332 J045 T179 1778-(ch2) 2. -NH-C (= 0)-K333 J012 T148 1779-(CH2) 2 · -NH-C (= 〇)-K333 J012 T164 1780-(ch2) 2- -NH-C (= 0)-K333 J013 T148 1781-(ch2) 2 · -NH-C (= 0) · K333 J013 T170 1782-(CH2 ) 2- -NH-C (= 0)-K333 J045 T170 1783-(CH2) r -NH-C (= 0)-K333 J045 T178 1784-(CH2) 2. -NH-C (= 0)-K333 J045 T179 1785-(CH2) 2- -NH_C (= 0)-K335 J012 T148 1786-(CH2) 2- -NH-C (= 0)-K335 J012 T164 1787 • (CH2) 2- -NH-C ( = 0)-K335 J013 T148 1788-(ch2) 2 · -NH-C (= 0 K335 J013 T170 1789-(CH2) 2- -NH-C (= 0)-K335 J045 T170 1790-(CH2) 2 --NH-C (= 0)-K335 J045 T178 1791-(CH 士 -NH-C (-O)-K335 J045 T179 1792-(CH2) 2- -NH-C (= 0)-K336 J012 T148 1793 • (CH2) 2 · -NH ^ C (= 0)-K336 J012 T164 1794-(ch2) 2- -NH-C (= 0〉-K336 J013 T148 1795-(CH2) 2- -NH-C (= 0)-K336 J013 T170 1796-(ch2) 2 · -NH-C (= 0)-K336 J045 T170 1797-(CH2) 2- -NH-C (= 0)-K336 J045 T178 1798 _ (c h2) 2- • NH-C (= 0) K336 J045 T179 1799-(CH2) 2- -NH-C (= 0) K340 J045 T170 1800-(ch2) 2. -NH-C (= 0) -K343 J045 T170

-181-200526665 (177) Compound numberA1- -A2- -g1-a3_a4-g2 -a5-r2 -a6-r3 1801-(〇η2) 2. -NH-C (= 0)-K345 J045 T169 1802 -(CH2) 2_ -NH-C (= 0)-K346 J045 T169 1803-(CH2) 2- • NH-C (= 0)-K346 J045 T170 1804-(CH2) 2- -NH-C (= 0 )-K355 J045 T148 1805-(CH2) 2- • NH-C (= 0)-K356 J045 T148 1806-(CH2) 2- -NH-C (= 0)-K357 J045 T148 1807-(CH2) 2- -NH-C (= 0)-K357 J045 T170 1808-(CH2) 2- -NH-C (= 0)-K358 J045 T148 1809-(CH2) 2- -NH-C (= 0 &gt; K358 J045 T170 1810 -(CH2) 2- -NH-C (= 0)-K359 J012 T170 1811-(ch2) 2 · -NH-C (= 0)-K359 J045 T170 1812-(CH2) 2_ -NH-C (= 0 )-K360 J012 T170 1813-(CH2) 2- -NH-C (= 0)-K360 J045 T170 1814-(CH2) 2 · -NH-C (= 0)-K361 J012 T170 1815 • (CH2) 2. -NH-C (= 0)-K361 J045 T170 1816-(CH2) 2- .NH-C (= 0 &gt;-K362 J012 T170 1817-(ch2) 2- -NH-C (= 0)-K362 J045 T170 1818-(CH2) 2- -NH-C (= 0)-K363 J012 T170 1819-(CH2) 2- -NH-C (= 0)-K363 J045 T170 1820-(ch2) 2,-NH-C ( = 0)-K364 J012 T170 1821-(CH2) 2. -NH-C (= 0)-K364 J045 T170 1822-(CH2) 2- -NH-C (= 0)-K365 J012 T170 1823 • (ch2) 2- -NH-C (= 0)-K365 J045 T148 1824-(CH2) 2- -NH'C (= 0)-. K365 J045 T170 1825-(CH2) 2 ·· 〇 (= 〇〉 · K366 J012 T170 -182- (178) Compound No.-A1 • A2- -G1_A3-A, G2 _a5-r2 1826-(ch2) 2- -NH-C (= 0)-K366 J045 T170 1827 • (ch2) 2- -NH-C (= 0). K367 J012 T170 1828-(ch2) 2- -NH-C (= 0)-K367 J045 T148 1829 • (CH2) 2- -NH-C (= 0 )-K367 J045 T170 1830-(CH2) 2- -NH-C (= 0)-K368 J012 T170 1831 • (ch2) 2 · -NH-C (= 0)-K368 J045 T170 1832-(CH2) 2- • nh-c (= o)-K369 J012 T170 1833-(CH2) 2- -NH-C (= 0)-K369 J045 T148 1834-(CH2) 2. -NH-0 (= O) «K369 J045 T170 1835-(CH2) 2. -NH-C (= 0) K370 J012 T170 1836-(CH2) 2- -NH-C (= 0)-K370 J045 T170 1837-(ch2) 2 · .NH-C ( = 0)-K371 J012 T170 1838-(CH2) 2- -NH-C (= 0). K371 J045 T170 1839-(ch2) 2. -NH-C (= 0)-K372 J012 T170 1840-(CH2) 2- -NH-C (= 0)-K372 J045 T170 1841-(ch2) 2. -NH-C (= 0)-K373 J012 T170 1842-(ch2) 2 · -NH-C (= 0)-K373 J045 T170 1843-(ch2) 2- -NH-C (= 0)-K374 J012 T148 1844-(CH2) 2_ -NH-C (= 0)-K374 J012 T170 1845-(CH2) 2- -NH-C (= 0)-K374 J045 T170 1846-(CH2) 2- • NH_C (= 0〉-K375 J012 T148 1847 _ (ch2) 2- -NH-C (= 0). K375 J012 T170 1848-(CH2) 2 · -NH-C (= 〇)-K375 J045 T170 1849-(CH2) 2 · -NH-C (= 0). K376 J012 T148 1850-(ch2) 2. -NH-C ( = 0)-K376 J012 T170 -183- (179) Compound number -A1_ • A2 · -g, a3-a4-g2 -a5-r2 -a6-r3 1851-(ch2) 2 · -NH-C (= 0 &gt; «376 J045 T170 1852-(CH2> 2- -NH-C (= 0)-K377 J012 T148 1853-(CH2) 2- -NH-C (= 0)-K377 J012 T170 1854-(CH2) 2- -NH-C (= 0)-K377 J045 T170 1855-(CH2) 2- -NH, C (= 0)-K378 J012 T148 1856-(CH2) 2- -NH-C (= 0)-K378 J012 T170 1857-(CH2) 2 · -0 (= 〇) · K378 J039 T170 1858-(CH2) 2- -NH-C (= 0)-K378 J044 T170 1859-(CH2) 2_ -NH-C (= 0) -K378 J045 T169 1860-(CH2) 2 · -NH-C (= 0)-K378 J045 T170 1861-(CH2): T -NH-C (= 0)-K379 J012 T148 1862-(ch2) 2-- NH-C (= 0 &gt; K379 J012 T170 1863-(ch2) 2. -NH-G (= 0) K379 J045 T169 1864-(CH2) 2- -NH-C (= 0)-K379 J045 T170 1865 • (CH2) 2- -NH-C (= 0 &gt; K380 J012 T148 1866-(CH2) 2- -NH-C (= 0)-K380 J012 T170 1867-(CH2) 2 -NH-C (= 0) * K380 J045 T170 1868-(ch2) 2. -NH-C (= 0)-K381 J012 T148 1869-(CH2) 2- -NH-C (= 0)-K381 J012 T170 1870-(CH2) 2_ -NH-C (= 0)-K381 J045 T169 1871-(CH2) 2 · -NH-C (= 0) · K381 J045 T170 1872-(ch2) 2- -NH-C (= 0)-K382 J007 T148 1873 • (ch2) 2- -NH-C (= 0)-K382 J008 T148 1874-(CH2) 2- -NH-C (= 0). K382 J010 T148 1875-(CH2> r -NH-C (= 0)-K382 J012 T148 -184- (180) Compound number -A1- • A2 _g, a3-a4-g2 -a5-r2 -a6-r3 1876-(ch2) 2- -NH -C (= 0)-K382 J012 T170 1877-(CH2) 2. -NH-C (= 0)-K382 J013 T148 1878-(CH2) 2- -NH-C (= 0)-K382 J014 T148 1879- (CH2) 2- -NH-C (= 0)-K382 J039 T170 1880-(CH2) 2- -NH-C (= 0)-K382 J044 T170 1881-(CH2) 2 · -NH-C (= 0 )-K382 J045 T169 1882-(ch2) 2--NH-C (= 0)-K382 J045 T170 1883-(CH2 &gt; 2- -NH-C (= 0)-K383 J012 T170 1884 • (CH2) 2- -NH-C (= 0)-K383 J045 T170 1885-(CH2) 2.-NH-C (= 0)-K384 J012 T148 1886-(CH2) 2, -NH-C (= 0)-K384 J012 T170 1887 • (ch2) 2- -NH-C (= 0)-K384 J039 Ding 170 1888-(CH2) 2_ -NH-C (= 0)-K384 J044 T170 1889 • (CH2) 2- -NH- C (= 0)-K384 J045 T169 1890-(CH2) 2- -NH-C (= 0)-K384 J045 T170 1891-(CH2) 2 · -NH-C (= 0 &gt; K385 J012 Ding 148 1892-( CH2) 2- -NH-C (= 0)-K385 J012 T170 1893-(CH2) r -NH-C (= 0)-K385 J045 T169 1894, (CH2) 2_ -NH-C (= 0)-K385 J045 T170 1895-(CH2) 2 · • NH-C &lt; = 0) · K386 J012 T148 1896-(CH2) 2- • NH-C (^ O)-K386 J039 T170 1897-(ch2) 2 '-NH- C (= 0). K386 J044 T170 1898 _ (CH2) 2 · • NH-C (= 0)-K386 J045 Ding 170 1899-(CH2) 2 · -NH-C (= 0)-K387 J012 T148 1900- (CH2) 2- -NH-C (= 0)-K387 J045 T170 -185- (181) Compound number -A1--A2- -g1-a3-a4-g2 -A, R2 -Ab-R3 1901-( CH2) 2- -NH-C (= 0)-K388 J012 T148 1902-(CH2) 2, -NH-C (= 0)-K388 J039 T170 1903-(CH2) 2- -NH-C (= 0) -K388 J044 T170 1904-(CH2) 2- -NH-C (= 0)-K388 J045 T170 1905 • (ch2) 2- -NH-C (= 0)-K389 J012 T148 1906 _ (CH2) 2-- NH-C (= 0)-K389 J045 T170 1907 • (CH2) 2- -NH-C (= 0) K390 J012 T148 1908-(ch2》 2 · -NH-C (= 0)-K390 J045 T170 1909 -(CH2) 2- -NH-C (= 0) K391 J012 T148 1910-(CH2) 2- -NH-C (= 0) K391 J045 T170 1911-(ch2) 2 · -NH-C (= 0)-K392 J012 T148 1912-(CH2) 2- -NH-C (= 0)-K392 J045 T170 1913-(ch2) 2- -NH-C (= 0)-K393 J012 T148 1914-(ch2) 2- -NH-C (= 0)-K393 J045 T170 1915-(ch2) 2. -NH-C (O)-K394 J012 T148 1916 • (CH2) 2- -NH-C (= 0)-K394 J045 T170 1917-(CH2) 2- -NH-C (= 0) K398 J012 T148 1918 • (ch2) 2- -NH-C (= 0)-K399 J010 T148 1919-(CH2 ) 2- -NH-C (= 0)-K399 J010 T170 1920-(CH2) 2- • NH-C (= 0)-K399 J012 T148 1921-(CH2) 2- -NH-C (= 0 &gt;- K399 J013 T148 1922-(ch2) 2- • NH-C (= 0〉-K399 J013 T170 1923 • (CH2) 2- -NH-C (= 0)-K399 J044 T170 1924-(ch2) 2_ NH-C (= 0)-K399 J045 T170 1925-(CH2) 2- -NH-C (= 0)-K399 J146 T148 -186 · 200526665 (182) Compound No.-A1- -A2- -G1-A3-A4-G2 -a6-r3 1926 • (CH2) 2_ -NH-C (= 0)-K399 J147 T148 1927-(ch2) 2- -NH-C (= 0)-K399 J150 T148 1928-(CH2> 2- -NH -C (= 0)-K399 J150 T170 1929-(CH2) 2- -NH-C (= 0)-K399 J151 T148 1930-(CH2) 2- -NH ^ C (= 0)-K399 J159 T148 1931- (CH2) 2-, NH-C (= 0) · K399 J159 T170 1932-(ch2) 2- -NH-C (= 0 &gt; K400 J012 T148 1933-(CH2) 2-- NH-C (= 0)-K400 J013 T170 1934-(ch2) 2- -NH-C (= 0)-K400 J045 T170 1935-(CH2) 2- -NH-C (= 0)-K400 J151 T148 1936 • (ch2) 2- -NH-C (= 0)-K400 J151 T170 1937-(ch2) 2- • NH-C (= 0)-K401 J012 T148 1938-(CH2) 2- -NH-C (= 0)-K401 J045 T170 1939-(CH2) 2. -NH-C (= 0)-K402 J012 T148 1940-(CH2) 2- -NH-C (= 0)-K402 J045 T170 1941-(CH2) 2 --NH-C (= 0)-K402 J151 T170 1942-(CH2) 2- -NH-C (= 0)-K402 J159 T148 1943-(CH2) 2- -NH-C (= 0)-K402 J159 T170 1944-(CH2) 2- • NH-C (= 0)-K403 J012 T148 1945-(CH2) 2- -NH «C (= 0)-K403 J013 T148 1946 • (ch2) 2- -NH-C (= 0)-K403 J013 T170 1947 • (CH2) 2. -NH-C (= 0) _ K403 J044 T170 1948-(CH2) r -NH-C (= 0)-K403 J045 T170 1949-(CH2) 2. • NH-C (= 0) · K403 J151 T148 1950-(CH2) 2 · -NH-C (= 0) · K403 J151 T170 -187- 200526665 (183) Compound number • A1--A2- .g1 .a3.a4.g2 -a5-r2 -a6-r3 1951-(CH2) 2_ -NH-C (= 0)-K403 J158 T170 1952-(ΟΗ2) 2- -NH-C (= 0)-K404 J012 T148 1953-(ch2) 2 · -NH-C (= 0)-K405 J012 T148 1954-(CH2) 2- • C (= 0)-K406 J012 Ding 148 1955-(ch2) 2 ·- NH-C (= 0)-K406 J045 T170 1956-(ch2) 2. -NH-C (= 0)-K407 J012 T148 1957-(CH2) 2- -NH-C (= 0)-K407 J013 T148 1958 • (ch2) 2- -NH-C (= 0)-K407 J013 Ding 170 1959-(CH2) 2- -NH-C (= 0). K407 J044 T170 1960 ， (CH2) 2- -NH-C ( = 0)-K407 J045 T170 1961-(CH2) 2- -NH-C (= 0 K408 J012 T148 1962-(CH2) 2- -NH-C (= 0)-K409 J012 T148 1963 • (CH2) 2 --NH-C (= 0)-K409 J045 Ding 170 1964-(CH2) 2 · -NH-C (= 0)-K410 J012 T148 1965 / (ch2) 2- -NH-C (= 0)-K411 J012 T148 1966-(CH2) 2- -NH-C (= 0)-K411 J045 Ding 170 1967-(CH2) 2- -NH ~ 0 (= 0) ~ K412 J012 T148 1968-(CH2) 2- -NH -C (= 0)-K413 J012 T148 1969-(CH2) 2- -NH-C (= 0)-K414 J012 T148 1970-(CH2) 2- -NH-C (= 0)-K414 J044 T170 1971- (ch2) 2. -NH-C (= 0)-K414 J045 T170 1972 • (ch2) 2, -NH-C (= 0). K415 J012 T148 1973-(CH2) r -NH-C (= 0) · K415 J013 T148 1974 • (CH2) 2- -NH-C (= 0)-K415 J013 T170 1975-(CH2) 2, -NH-C (= 0)-K415 J044 T170

-188- (184) Compound number -A1- -A2- -g1-a3-a4-g2 -As-R2 -a6-r3 1976-(CH2) 2- -NH-C (= 0)-K415 J045 T170 1977 • (CH2) r -NH-C (= 0)-K415 J151 T148 1978-(ch2) 2- -NH-C (= 0)-K415 J151 T170 1979-(CH2) 2_ -NH-C (= 0) -K415 J158 Ding 170 1980-(ch2) 2- -NH-C (= 0)-K416 J012 T148 1981 • (CH2) r -NH-C (= 0)-K417 J012 T148 1982-(CH2) 2-- NH-C (= 0)-K418 J012 T148 1983-(CH2) 2- -NH-C (= 0)-K419 J012 T148 1984-(CH2) 2- -NH-C (= 0). K419 J045 T170 1985 -(CH2) 2- -NH-C (= 0)-K420 J012 T148 1986-(CH2) r -NH-C (= 0)-K420 J013 T148 1987-(CH2) 2- -NH-C (= 0 )-K420 J013 T170 1988-(CH2) 2- -NH-C (= 0)-K420 J044 T170 1989-(ch2) 2. -NH-C (= 0)-K420 J045 T148 1990-(CH2) 2- • NH-C (= 0)-K420 J045 T170 1991-(ch2> 2- -NH ^ C (= 0)-K420 J149 T148 1992-(CH2) 2- -NH-C (= 0) K420 J150 T148 1993-(CH2) 2. -NH-C (= 0)-K420 J150 T170 1994-(ch2) 2. -NH-C (= 0)-K420 J151 T148 1995-(CH2) r -NH-C (= 0) · K420 J151 T170 1996-(ch2) 2_ -NH-C (= 0)-K420 J158 T170 1997 ， (ch2) 2- -NH-C (= 0) · K421 J012 T148 1998-(CH2) 2- -NH-C ( = 0)-K422 J012 T148 1ΘΘ9-(CH2) 2- • NH-C (= 0)-K423 J012 T148 2000-(CH2) r -NH-C (= 0)-K424 J012 T148 -189- 200526665 (185 ) Compound No.A1- -A2- -g1-a3-a4-g2 -As-R2 -A, R3 2001-(CH2) 2- -NH-C (= 0)-K425 J012 T148 2002-(CH2) 2 --NH-C (= 0)-K426 J012 T148 2003-(CH2) r • NH-C (= 0)-K200 J022 T170 2004-(CH2) 2- -NH-C (= 0)-K357 J012 T148 2005 _ (CH2) 2--NH-C (= 0) -NH- K005 J045 T148 2006 -d -NH-C (= 0) -NH- K008 J045 T148 2007-(ch2) 2- -NH-C ( = 0) -NH- K023 J012 T148 2008-(CH2) 2- ”NH-C (= 0) -NH · K033 J012 Ding 148 2009 • (CH2) 2_ -NH-C (= 0) -NH- K077 J045 T148 2010-(ch2) 2. -NH-C (= 0) -NH- K102 J045 T148 2011-(ch2) 2- -NH-C (= D) -NH- K102 J045 T170 2012-(CH2) 2- -NH-C (= 0) -NH- K106 J045 T148 2013 • (ch2) 2- -NH-C (= 0) -NH · K336 J012 T148 2014-(ch2) 2- -NH_C (= 0) -NH -K204 J045 T148 2015-(ch2) 2- -NH-C (= 0) -NH- K204 J045 T170 2016-(CH2) 2- -NH_C (= 0) -NH- K223 J045 T148 2017-(CH2) 2 --NH-C (= 0) .NH- K230 J012 Ding 148 2018-(ch2) 2- -NH-C (= 0) -NH- K231 J012 T148 2019-(CH2) 2- -NH-C (= 0) -NH- K248 J045 T148 2020-(CH2) 2- -NH-C (= 0) -NH- K249 J045 T148 2021-(CH2) 2- -NH-C (= 0) -NH- K250 J045 T148 2022-(CH2> 2- -NH-C (= 0) -NH- K278 J012 Ding 148 2023-(CH2) 2- -NH-C (= 0) -NH- K277 J045 T148 2024-(ch2) 2 · -NH-C ( = 0) -NH- K277 J045 T170 2025 • (CH2) 2- -NH-C (= 0) -NH- K278 J045 T148

-190- 200526665 (186) Compound number -A1- -A2 · -g1-a3-a4-g2 • a5-r2 -a6-r3 2026-(CH2) 2 · -NH-C (= 0) -NH- K278 J045 T170 2027-(CH2) 2- -NH-C (= 0) -NH- K279 J045 T148 2028-(CH2) 2- -NH-C (= 0) -NH- K286 J045 T148 2029-(ch2) 2 -NH-C (= 0) -NH- K324 J045 T148 2030-(CH2) 2- -NH-C (= 0) -NH- K324 J045 T170 2031-(CH2) 2- -NH-C (= 0 ) -NH- K325 J012 T148 2032-(CH2> 2- -NH-C (= 0) -NH- K325 J045 T148 2033-(CH2) 2 · -NH-C (= 0) -NH- K325 J045 T170 2034 -(CH2) 2- -NH-C (= 0) -NH- K326 J045 T148 2035-(CH2) 2- -NH-C (= 0) -NH- K326 J045 T169 2036-(GH2) 2- -NH .C (= 0) -NH- K326 J045 T170 2037-(CH2) 2- -NH-C (= 0) -NH- K327 J045 T170 2038-(CH2) 2- -C (= 0〉 -NH- K328 J045 T170 2039-(CH2): r -NH-C (= 0) -NH- K329 J045 T170 2040-(CH2) 2- -NH-C (= 0) -NH- K330 J012 T148 2041-(CH2) 2 --NH-C (= 0) -NH. K330 J045 T170 2042 • (CH Shi · -NH-C (= 0) -NH- K331 J012 T148 2043-(CH2) 2. -NH-C (= 0) -NH- K331 J045 T170 2044 • (ch2) 2- -NH-C (= 0) -NH- K332 J045 T169 2045-(CH2) 2- -NH-C (= 0) -NH- K332 J045 T170 2046- (CH2) r -NH-C (= 0) -NH- K33 3 J012 T148 2047 • (CH2) 2- -NH-C (= 0) -NH- K333 J044 T170 2048-(CH2) r -NH-C (= 0) -NH- K333 J045 T169 2049-(CH2〉 2 --NH-C (= 0) .NH. K333 J045 T170 2050 • (CH2) 2 · -NH-C (= 0) -NH- K334 J045 T170 -191-(187) Compound No.-A1- • A2 · -G, A3-A4-G2 -a6-r2 -A, R3 2051-(CH2) r -NH-C (= 0) -NH- K335 J044 T170 2052-(0 ^ 2) 2--NH-C ( = 0) -NH- K335 J045 T148 2053-(ch2) 2 · -NH-C (= 0) -NH- K335 J170 T170 2054-(ch2) 2. -NH-C (= 0) -NH- K336 J012 T170 2055-(CH2) 2- -NH-C (= 0) -NH- K336 J044 T170 2056 '(CH2) 2- -NH-C (= 0) -NHK336 J045 T148 2057-(CH2) 2- • NH-C (== 0) -NH · K336 J045 T169 2058-(CH2) 2- -NH-C (= 0) -NH · K336 J045 T170 2059-(CH2) 2. -NH-C (= 0 ) -NH- K337 J045 T170 2060-(CH2) 2- -NH-C (= 0) -NH- K338 J045 T148 2061-(CH2) 2- -NH-C (= 0) -NH- K338 J045 T170 2062 -(ch2) 2- -NH-C (= 0) -NH- K339 J045 T148 2063-(CH2) 2 · -NH-C (= 0) -NH- K339 J045 T170 2064 _ (CH2) 2- -ISIH -C (= 0) -NH- K340 J012 T148 2065-(CH2) 2. -NH-C (= 0) -NH- K340 J045 T148 2066-(CH2) 2- -NH-C (= 0) -NH -K340 J045 T169 2067-(CH2) 2- -NH- C (= 0) -NH- K340 J045 T170 2068-(CH2) 2- -NH-C (= 0) -NH- K341 J045 T148 2069 _ (CH2) 2 · -NH-C (= 0) -NH- K341 J045 T170 2070-(CH2) 2- -NH-C (= 0) -NH- K342 J045 T148 2071 _ (CH2) r -NH-C (= 0) -NH- K342 J045 T170 2072-(CH2) 2 -NH-C (= 0) -NH- K343 J045 T148 2073 • (CH2) 2 · -NH-C (= 0) -NH- K343 J045 T170 2074-(ch2) 2- -NH-C (= 0 ) -NH- K344 J045 T170 2075-(CH2) 2- -NH-C (= 0) -NH- K345 J045 T170 -192- 200526665 (188) Compound number -A'- -A2- -g1-a3- a4-g2 A, R2 -Ae-R3 2076-(ch2) 2- -NH-C (= 0) -NH- K346 J045 T17D 2077-(CH2) 2- -NH-C (= 0) -NHK347 J045 T170 2078-(CH2) 2- -NH-C (= 0) -NH- K348 J045 T148 2079 • (CH2) 2- -NH-C (= 0) -NH- K348 J045 T170 2080 &gt; (ch2) 2. -NH-C (= 0) -NH- K349 J045 T170 2081-(CH2) 2 · -NH-C (= 0) -NH- K350 J045 T148 2082 • (ch2) 2- -NH-C (= 0) -NH- K350 J045 T170 2083-(CH2) 2 · -NH-C (= 0) -NH-, K351 J045 T148 2084-(CH 山 ·· NH-C (= 0) -NH- K351 J045 T170 2085-(CH2) r -NH-C (= 0) -NH- K352 J045 T148 2086-(CH2) 2- -NH-C (= 0) -NH- K352 J045 T170 2087 • (ch2) 2, -NH -C (= 0) -NH- K353 J045 T148 2088-(CH2) 2- -NH-C (= 0) -NH- K353 J045 T170 2089-(ch2) 2. -NH-C (= 0) -NH- K354 J045 T148 2090 • (CH2) 2-- NH-C (= 0) -NH- K354 J045 T170 2091-(ch2) 2- -NH-C (= 0) -NH- K355 J045 T170 2092-(CH2) 2- -NH-C (= 0)- NH- K356 J045 T170 2093-(ch2) 2- -NH-C (= 0) -NH- K359 J045 T148 2094-(ch2) 2 · -NH-C (= 0) -NH- K360 J045 T148 2095-( ch2) 2- -NH «C (= 0) -NH- K362 J045 T148 2096-(CH2) r -NH-C (= 0) -NH- K361 J045 T148 2097-(CH2) 2- -NH-C ( = 0) -NH- K362 J045 T170 2098-(CH2) r -NH-C (= 0) -NH- K364 J045 T170 2099-(CH2) 2- -NH-C (= 0) -NH- K370 J045 T148 2100-(CH2) 2 * &quot; -NH-C (= 0) -NH- K371 J045 T148 -193-(189) Compound number -A1_ -A2- -Gn-A3-A, G2 -a5-r2 -A , R3 2101-(ch2) 2- -NH-C (= 0) -NH- K373 J045 T148 2102-(CH2) r -NH-C (= 0) -NH- K431 J045 T170 2103-(ch2) 2_- NH-C (= 0) -NH- K395 J012 T148 2104-(CH2) 2 · -NH-C (= 0) -NH- K395 J045 T170 2105-(CH2) 2- -NH-C (= 0)- NH- K396 J012 T148 2106-(CH2) 2- -NH-C (= 0) -NH- K396 J045 T170 2107-(CH2) r -NH-C (= 0) -NH- K397 J012 T148 2108-(CH2 ) 2- -NH-C (= 0) -NH- K397 J045 T170 2109 • (ch2) 2- -NH-0 (= O) · K241 J045 T148 2110 • (CH2) 2- -NH-C (= 0) -0- K005 J001 T148 2111 * (CH2) 2_ -NH-C (= 0) -0- K005 J007 T148 2112-(ch2) 2 · -NH-C (= 〇) -0- K005 J008 T148 2113-(ΟΗ2) 2- -NH-C (= 0) -0- K005 J009 T170 2114-(ch2) 2- -NH-C (= 0) -0- K005 J010 T148 2115-(CH2) 2- -NH-C (= 0) -0- K005 J011 T170 2116-(CH2) 2 --NH-C (= 0) -0- K005 J012 T170 2117-(CH2) 2- • NH-C (= 0) -0- K005 J013 T148 2118-(CH2) 2- -NH-C (= 0 ) ·. K005 J014 T148 2119 • (CH2) 2. • NH_C (= 0 Bu 0- K005 J015 T170 2120-(CH2) 2. -NH-C (= 0) _0- K005 J026 T001 2121 • (CH2) 2_ -NH -C (= 0) -O K005 J026 T148 2122 • (ch2) 2 · -NH-C (= 0) -0- K005 J026 T170 2123-(CH2) 2 · -NH-C (= 0) -0- K005 J037 T170 2124-(CH2) 2 · -NH-C (= 0) -0- K005 J039 T170 2125-(CH2) r -NH-C (= 0) -0- K005 J043 T170 -194- 200526665 (190 ) Compound number A1- -A2- -g1-a3-a4-g2 • As-R2 -a6-r3 2126-(CH2) 2, -Ν -Α {= 0) · 0 K005 J045 T072 2127-(CH2) 2- -NH-C (= 0) -0- K005 J045 T074 2128 e (CH2) 2_ -NH-C (= 0) -0- K005 J045 T180 2129-(ch2) 2- -NH-C (= 0)- 0- K005 J047 .T170 2130 • (CH2) 2- -NH-C (= 0) -0- K005 J079 T170 2131-(CH2) 2- • NH-C (= 0) .〇. K005 J080 T148 2132- (ch2) 2- -NH-C (= 0) -0- K005 J081 T148 2133-(CH2) r -NH-C (= 0) -0- K005 J082 T148 2134-(CH2) 2 · -NH-C (= 0) -0- K005 J090 T148 2135-(CH2) 2. -NH-C (= 0) -0- K005 J092 T148 2136-(CH2) 2 · -NH-C (= 0) -0- K005 J103 T170 2137 -NH-C (= 0) -0- K005 J104 T170 2138-(CH2) 2. • NH-C (= 0) -0- K005 J105 T170 2139-(CH2) 2- -NH-C ( = 0)- 0- K005 J106 T170 2140-(ch2) 2_ -NH-C (= 0) -0- K005 J107 T170 2141 • (CH2) 2. -NH-C (= 0) -0- K005 J140 T001 2142-(ch2 ) 2- -NH-C (= 0) -0- K005 J140 T148 2143-(ch2) 2. -NH-C (= 0) -0- K005 J140 T170 2144-(ch2) 2- -NH-C ( = 0) -0- K005 J144 T148 2145-(CH2) 2 · .NH-C (= 0) -0 · K005 J146 Ding148 2146-(CH2): r -NH-C (= 0) -0- K199 J045 T148 2147-(CH2): r -NH-C (= 0) -0- K223 J045 T148 2148 • (CH2) 2- -NH-C (= 0) -0- K198 J045 T148 2149 • (ch2) 2 -NH-S (= 0) 2- K200 J012 T148 2150-(ch2) 2.-NH-S (= 0) r K200 J044 T170 (191) Compound number-A1- -A2- -g1-a, a4 -g2 -As-R2 • A, R3 2151-(CH2) 2_ -NH-S (= 0) 2 · K200 J045 T170 2152-(CH2> 2- -NH-S (= 0) 2 · K223 J012 T148 2153 -(CH2) 2- -NH-S (= 0) r K223 J044 T170 2154-(ch2) 2 · -s (= o) 2- K230 J044 T170 2155-(CH2) 2 · nh-s (= o ) 2- K230 J045 T170 2156-(CH; 2> 2- -NH-S (= 0) 2 · K231 J044 T170 2157-(CH2) 2- .NH-S (= 0) 2- K231 J045 T170 2158- (CH2) 3- -C (= 0)-K108 J001 T148 2159-(CH2) 3 · -C (= 0) _ K108 J022 T170 2160-(CH2) 3- -C (= 0)-K109 J029 T170 2161 • (CH2) 3- -c (= o)-K112 J012 T148 2162-(CH2) 3. -C (= o)-K112 J012 T170 2163-(CH2) 3- -C (= 0)-K112 J037 T170 2164-(CH2 ) 3- -c (= o)-K112 J043 T170 2165-(CH2) 3- -C (= 0)-K112 J138 T148 2166-(CH2) 3 · • c (= o)-K112 J138 T170 2167-( CH2) 3- • C (= 0). K112 J144 T148 2168-(CH2) r • C (= 0)-K112 J144 T164 2169-(CH2) 3- -C (= 0)-K112 J144 Ding 169 2170- (CH2) 3_ -c (= o)-K112 J144 T170 2171-(CH2) 3 · -c (= o〉-K116 J012 T148 2172-(ch2) 3- -C (= 0)-K121 J043 T170 2173- (CH2) 3, -C (= 0)-K129 J012 T148 2174-(CH2) 3- -C (= 0)-K136 J044 T170 2175 • d -C (= 0)-K137 J012 T148 -196- (192 ) Compound No.-A1--A2- -g1-a3-a4-g2 -As-R2 -a6-r3 2176-(CH2) 3 · -C (= 0)-K137 J012 T170 2177-(CH2) 3- * C (-0) * K137 J045 T170 2178-(CH2) 3- -c (= o)-K138 J079 T170 2179-(CH2) 3- -C (= 0)-K139 J012 T148 2180-(CH2) 3- -C (= 0)-K142 J012 T148 2181-(CH2) 3 · -C (= 0)-K143 J012 T148 2182-(CH2) 3- -C (-0)-K144 J012 T148 2183-(CH2) g --C (= 0)-K144 J043 T148 2184-(CH2) 3_ • C (= 0)-K144 J043 T170 2185-(CH2) 3- -c (= o) _ K144 J138 T148 2186-(ch2) 3- K144 J138 T170 2187 • (CH2) 3 · -0 (= 0)-K144 J144 T148 2188-(CH2) 3- -c (= o) -K144 J144 T170 2189-(CH2) 3- -C (= 0)-K147 J012 T148 2190-(CH2) 3- • c (= o) _ K147 J138 T170 2191-(CH2) 3 * -C (= 0 )-K148 J012 T148 2192-(CH2) 3 · -c (= o)-K148 J139 Ding 170 2193 • (CH2) 3- -c (= o)-K150 J012 T148 2194-(CH2) 3- -c ( = o)-K154 J012 T148 2195-(CH2) 3-, c (= o)-K166 J012 T148 2196-(CH2) 3- -C (= 0)-K166 J144 T170 2197-(CH2) 3 · -C (= 0)-K170 J007 T170 2198-(CH2) 3 · -C (= 0)-K172 J012 T170 2199-(CH2) s · -C (= 0)-K237 J012 T148 2200-(CH2) 3-- C (= 0)-K391 J144 T170 -197- (193) Compound No.-A1--A2- -g1-a3-a4-g2 -a5-r2 -A, R3 2201-(ch2) 3- -C (= 0) -NH- K004 J012 T148 2202-(CH2) 3- -C (= 0) -NH- K009 J001 T148 2203 • (ch2) 3- -C (= 0) -NH- K009 J007 T148 2204-(CH2 ) 3- -C (= 0) -NH- K009 J007 Ding 164 2205-(CH2) 3- -C (= 0) -NH- K009 J007 T169 2206-(CH2) 3_ -C (= 0) -NH- K009 J007 T170 2207-(CH2) 3. -C (= 0) -NH- K009 J012 T148 2208-(CH2) 3- -C (= 0) -NH- K009 J037 T17 0 2209-(CH2) 3- -C (= 0) -NHK012 J001 T148 2210-(CH2) 3- -C (= 0) -NH- K013 J012 Ding 148 2211-(CH2) 3- -C ( = 0) -NH- K013 J012 T170 2212-(CH2) 3. -C (= 0) -NH- K023 J012 T148 2213 ， (CH2) 3 · -C (= 0) -NH- K023 J029 T148 2214-( CH2) 3- • C (= 0) -NH- K023 J029 T164 2215 _ (CH2) 3- -C (= 0) -NH- K023 J029 T169 2216-(CH2) 3_ -C (= 0) -NH- K023 J029 T170 2217-(CH2) 3 · -C (= 0) -NH- K023 J043 T170 2218-(CH2) 3- • C (= 0) _NH- K029 J012 T148 2219-(CH2) 3- -C ( = 0〉 -NH- K029 J044 T148 2220-(CH2) 3 · -C (= 0) -NH- K029 J044 T164 2221-(CH2〉 3- -C (= 0〉 -NH- K029 J044 T169 2222-( CH2) 3- • c (= 〇hsih- K029 J044 T170 2223-(CH2) 3 · -C (= 0) -NH- K029 J045 T170 2224-(CH2) 3- -C (= 0) -NH- K033 J012 T148 2225-(CH2) 3- -C (= 0) -NH- K033 J043 T148 -198- 200526665 (194) Compound No.-A1- -A2. -G, a3-a ~ g2 • A, R2 -a6 -r3 2226-(CH2) 3- -C (= Q) -NH- K033 J043 T164 2227-(CH2) 3. -C (= 0〉 -NH- K033 J043 T169 2228-(CH2) 3- -C ( = 0) -NH- K033 J043 T170 2229 _ (CH2) 3, -C (= 0) -NH- K033 J044 T170 2230-(CH2) 3- K034 J012 T14 8 2231-(CH2) 3- -C (= 0) -NH- K034 J045 T148 2232-(CH2) 3- -C (= 0) -NH- K034 J045 T164 2233 • (CH2) 3- -C (= 0) -NH- K034 J045 T169 2234-(CH2) 3_ _C (= 0) -NH- K034 J045 T170 2235-(CH2) 3- -C (= 0) -NH- K034 J079 T170 2236-(CH2) 3 --C (= 0) -NH- K077 J138 T170 2237-(CH2) 3 · -C (= 〇HslH- K078 J139 T170 2238-(CH2) 3. -C (= 0) -NH- K101 J144 T170 2239 -(CH2) 3- -C (= 0) -NH- K102 J007 T170 2240-(CH2) 3. -C (= 0) -NH- K102 J012 T148 2241-(CH2) 3- -C (= 0) -NH- K102 J012 T170 2242-(CH2) 3- -C (= 0) -NH- K102 J079 T148 2243-(CH2) 3- -C (= 0) -NH- K102 J079 T164 2244-(CH2) 3 --C (= 0) -NH- K102 J079 T169 2245-(CH2) 3- • C (= 0) _NH- K102 J079 T170 2246-(CH2) 3- _C (= 0) -NH- K103 J012 T148 2247 -(CH2) 3_ -C (= 0) -NH- K103 J138 T148 2248-(CH2) 3- -C (= 0) -NH- K103 J138 T164 2249-(CH2) 3- -C (= 0)- NH- K103 J138 T169 2250 _ (CH2) 3- -C (= 0) -NH- K103 J138 T170

-199- (195) Compound number -A1 · A2- -G1-A3-Aa-G2 -a5-r2 -a6-r3 2251-(CH2) 3- -C (= 0) -NH- K104 J012 T148 2252 , (CH2) 3- -C (= 0) -NH · K104 J012 T170 2253-(CH2) 3- -C (= 0) -NH- K104 J139 Ding 148 2254-(CH2) s. -C (= 0 ) -NH- K104 J139 T164 2255-(CH2) 3- ~ C (= 0) ** NH ~ K104 J139 T169 2256 • (CH2) 3_ -C (= 0) -NH- K104 J139 T170 2257-(CH2) 3_ • C (= 0〉 -NH- K108 J012 T148 2258-(CH2) 3- -C (= 0) -NH- K198 J012 T148 2259-(CH2) 3. -C (= 0) -NH- K198 J022 T170 2260-(CH2) 3, -C (= 0) -NH- K200 J012 T148 2261-(CH2) 3- -C (= 0) -NH- K200 J029 T170 2262-(CH2) 3- -C (= 0) -NH- K201 J012 T148 2263-(CH2) 3- -C (= 0) -NH- K201 J037 T170 2264-(CH2) 3- -C (= 0) -NH- K204 J002 T148 2265-(CH2 ) 3. -C (= 0) -NH- K204 J012 T148 2266-(CH2) 3_ -C (= 0) -NH- K204 J012 T170 2267-(ch2) 3- -C (= 0) -NH- K204 J043 T148 2268-(CH2) 3- -C (= 0) -NH- K204 J043 T170 2269-(CH2) 3- -C (= 0) -NH- K204 J138 Ding 170 2270-(CH2) 3- -C (= 0) -NH- K204 J139 T148 2271-(CH2) 3. -C (= 〇) _NH- K204 J144 T148 2272-(CH2) 3_ -C (= 0) -NH- K204 J144 T170 2273-(CH 2) 3- -C (= 0) -NH- K215 J012 T148 2274-(CH2) 3- -C (= 0) -NH- K216 J007 T170 2275-(CH2) 3- -C (= 0) .NH -K216 J012 T148 -200- 200526665 (196) Compound number -A1- -A2 · -g1-a3-a4-g2 -A, R2 -a6-r3 2276 _ (CH2) 3_ -C (= 0) -NH- K216 J012 T164 2277-(CH2) 3- -C (= 0) -NH- K216 J012 T170 2278-(ch2> 3- -C (= 0) -NHK216 J022 T170 2279-(ch2) 3- -C (= 0) -NHK216 J029 T170 2280-(CH2) 3- • C (= 0) -NH- K216 J037 T170 2281-(CH2) 3- -C (= 0) -NH ^ K216 J043 T148 2282- (CH2) 3- -C (= 0) -NH- K216 J043 T170 2283-(CH2) 3 · -C (= 0) -NH- K216 J044 T169 2284-(CH2) 3- -C (= 0)- NH- K216 J044 T170 2285-(CH2) 3- -C (= 0) -NH_ K216 J045 T170 2286-(CH2) 3- -C (= 0) -NH- K216 J079 T170 2287-(CH2) 3-- C (= 0) .NH- K216 J138 T148 2288-(CH2) 3- -C (= 0) -NH- K216 J138 T170 2289-(CH2〉 3- -C (= 0) -NH- K216 J139 T170 2290 -(CH2) 3- -C (= 0) -NH- K216 J144 T148 2291-(CH2〉 3- -C (= 0) -NH- K216 J144 T170 2292-(CH2) 3. -C (= 0) -NH- K223 J001 T148 2293-(CH2) 3 · -C (= 0) -NH- K223 J045 T170 2294-(CH2) 3- • C (= 0) -NH- K224 J079 T170 2295-(CH2) s --C (= 0) -NH- K225 J138 T170 2296-(CH2) 3 &gt;-C (= 0) -NH- K229 J012 Ding 148 2297-(CH2) 3 · -C (= 0) -NH- K229 J139 T170 2298 -(CH2) 3- -C (= 0) -NH- K234 J012 T148 2299 • (CH2) r -C (= 0) -NH- K198 J001 T148 2300-(CH2) 3- -C (= 0)- NH- K244 J001 T148 -201-200526665 (197) Compound number -A1- • A2 · -gW-g2 -As-R2 -A, R3 2301-(CH2) 3- -C (= 0) -NH- K246 J001 T148 2302-(CH2) 3- -C (= 0) -NH- K280 J012 T148 2303-(CH2) 3- -C (= 0) -NHK293 J144 T170 2304-(CH2> 3- -C (= 0) -NH- K323 J007 T170 2305-(CH2) 3- -C (= 0) -NH- K324 J012 T148 2306-(CH2v -C (= 0) -NH- K324 J012 T170 2307-(CH2) 3- -C (= 0) -NH · K325 J022 T170 2308-(CH2) 3_ • C (= 〇HSlH- K326 J029 T170 2309-(CH2) 3- -C (= 0) -NH- K327 J037 T170 2310-( CH2) 3 · K333 J007 T170 2311-(CH2) 3- -C (= 0) -NH- K333 J012 T148 2312-(CH2) 3 · -C (= 0) -NH- K333 J012 T170 2313-(CH2) 3- -C (= 0) -NH ~ K333 J022 T170 2314-(CH2) 3- -C (= 0) -NH- K333 J029 T170 2315-(ch2) 3. -C (= 0) -NH- K333 J037 T170 2316-(CH2) 3- -C (= 0) -NH- K333 J043 T170 2317-(CH2) 3- -C (= 0) -NH- K333 J04 4 T170 2318-(CH2) 3_ -C (= 0) -NH ~ K333 J045 T170 2319-(CH2) 3- _C (= 0) -NH- K333 J079 T170 2320-(CH2) a- .C (= 0 ) -NH ^ K333 J138 T170 2321 ， (CH2) 3- -C (= 0) -NH · K333 J139 T170 2322-(CH2V -C (= 0) -NH- K333 J144 T170 2323-(CH2) 3-- C (= 0) -NH- K334 J043 T170 2324-(CH2) 3_ -C (= 0) -NH- K335 J044 T170 2325-(ch2) 3- -C (= 0) -NH ^ K336 J012 T148 -202 -200526665 (198) Compound No.-A1- • A2- -GW-G2 -a5-r2 -a6-r3 2326 (ch2) 3- -C (= 0) -NH- K340 J045 T170 2327-(CH2) 3- -C (= 0) -NH- K343 J012 T148 2328-(CH2) 3- -C (= 0) -NH- K343 J079 T170 2329-(CH2) 3- -C (= 0) -NH- K344 J012 T148 2330-(ch2) 3- -C (= 0) -NH- K346 J007 T170 2331-(CH2) 3- -C (= 0) -NH- K346 J012 T148 2332-(CH2) 3 · -C (= 0 ) -NH- K346 J012 T170 2333-(CH2) 3- -C (= 0) -NH- K346 J022 T170 2334-(CH2) y -0 (= 〇) -ΝΗ ~ K346 J029 T170 2335-(CH2) 3 --C (= 0) -NH- K346 J037 T170 2336-(CH2> 3- -C (= 0) -NH · K346 J043 T148 2337-(CH2) 3 · • C (= 0) -NH- K346 J043 T170 2338-(CH2) 3- -C (= 0) -NH- K346 J044 T170 2339-(CH2) 3 · -C (= 0) -NH- K346 J045 T170 2340-(C H2) r -C (= 0) -NH- K346 J079 T170 2341-(CH2) 3- -C (= 0) -NH- K346 J080 / J081 T148 2342-(CH2) 3- -C (= 0)- NH- K346 J090 T148 2343-(CH2) 3- -C (= 0) -NH- K346 J100 T148 2344-(CH2) 3 · -C (= 0) -NH- K346 J138 T148 2345-(CH2) r- C (= 0) -NH- K346 J138 T170 2346-(CH2) 3- • C (= 0) -NHK346 J139 T170 2347 • (CH2) 3- -C (= 0) -NHK346 J144 T148 2348 -(CH2) 3- -C (= 0) -NH · K346 J144 T170 2349-(CH2): T • c (= o) ·· K347 J138 T170 2350-(CH2) 3- -C (= 0)- NH- K353 J012 T148 -203- (199) Compound number -A1- -A2 · -g, a3_a4-g2 -As-R2 -a6-r3 2351-(CH2) 3--c (= o) · K370 J139 T170 2352-(CH2) 3- -C (= 0) -NH- K427 J012 T148 2353 _ (ch2) 3- -C (= 0) -NH- K428 J045 T170 2354-(CH2) s- -C (= 0) -NH- K429 J012 T148 2355-(CH2) 3- -C (= 0〉 -NHK430 J045 T170 2356 _ (ch2) 3- -C (= 0)-K240 J012 T148 2357-(ch2) 3 --C (= 0) · K240 J012 T170 2358-(CH2) 3- ** 0 (= 0) -0- K001 J002 T148 2359-(ch2) 3- -C (= 0) ·. -K001 J007 T170 2360-(CH2) 3- -c (= o) _o- K001 J012 T148 2361-(CH2) 3- -C (= 0) -0- K002 J044 T170 2362-(CH2) 3- -C (= 0) -0- K197 J002 T148 2363-(CH2) 3, -C (= 〇l〇K197 J012 T148 2364-(CH2) a- -C (= 0) -0 · K197 J012 T170 2365-(CH2 ) 3- C (= 0) -0- K197 J045 T170 2366-(ch2) 3- -NH- K185 J007 T14 & 2367-(CH2) 3- -NH- K185 J044 T170 2368-(CH2) 3- -NH -C (= 0)-K005 J007 T148 2369-(CH; 2) 3- -NlH-0 (= O)-K005 J044 T170 2370-(CH2) 3- -NH-C (= OJ- K007 J012 T148 2371 -(CH2) 3- -NH-C (= 0)-K007 J045 Ding 170 2372-(CH2) 3--NH-C (= 0)-K008 J012 T148 2373-(CH2) r _NH-C (= 0 )-K008 J045 T170 2374-(CH2) 3- -NH-C (= 0)-K009 J007 T148 2375 • (ch2) 3- • NH-C (= 0) _ K009 J044 T170 -204- (200) Compound Number -A1- -A2 · -g1-a3-a4-g2 -As-R2 • a6-r3 2376-(ch2) 3- -NH-C (= 0)-K011 J007 T148 2377-(ch2) 3:- NH-C (= 0)-K011 J044 T170 2378-(CH2) 3- -NH-C (= 0)-K013 J007 T148 2379-(CH2) 3- • NH-C (= 0) K013 J044 T170 2380 -(CH2> 3- -NH-C (= 0)-K051 J012 T148 2381-(CH2) 3- -NH-C (= 0)-K051 J045 T170 2382- (ch2) 3- -NH ~ C (= 0)-K200 J012 T148 2383-(CH2) 3- -NH-C (= 0)-K2D0 J045 T170 2384-(CH2) 3- -NH-C (= 0 )-K204 J007 T148 2385-(CH2) 3- -NH-C (= 0)-K204 J044 T170 2386-(CH2) 3- -NH-C (= 0)-K208 J012 T148 2387-(CH2) 3- -NH-C (= 0)-K208 J045 T170 2388-(CH2) 3- -NH-C (= 0) «K212 J012 T148 2389 • (CH2) 3- -NH-C (= 0) K212 J045 T170 2390-(CH2) 3- -NH-C (= 0)-K262 J012 T148 2391-(CH2) 3- -NH-C (= 0)-K262 J045 T170 2392-(ch2) 3 · -NH-C ( = 0)-K263 J007 T148 2393-(CH2) 3- -NH-C (= 0)-K263 J044 T170 2394 • (CH2) 3- -NH-C (= 0)-K266 J007 T148 2395 _ (ch2) 3- -NH-C (= 0)-K266 J044 T170 2396 _ (CH2) 3- -NH-C (= 0). K272 J012 T148 2397 ta (CH2) 3- -NH-C (= 0)-K272 J045 T170 2398 • (CH2) 3- ~ NH-C (= 0)-K293 J007 T148 2399 ~ (CH2) 3- -NH-C (= 0) K293 J044 T170 2400 • (CH2) 3- -NH- C (= 0) -NH- K033 J012 T148 -205- 200526665 (201) Compound No.-A1- -A2 · -G1-A3-A Gas G2 • A5.R2 -Ae-R3 2401-(ch2) 3-- NH-C (= 0) -NH- K033 J045 T170 2402-(CH2) 3- -NH-C (= 0) -NH- K333 J007 T148 2403-(CH2) 3 · C (= 0) -NH- K333 J044 T170 2404-(CH2) 3_ • NH-C (= 〇HslH- K336 J012 T148 2405-(CH2) s- -NH-C (= 0) -NH- K336 J045 T170 2406 Single bond single bond K001 J002 T170 2407 Single bond Single key K001 J007 T148 2408 Single key K001 J007 T170 2409 Single key K001 J012 T148 2410 Single key K001 J012 T170 2411 Single key K001 J029 T148 2412 Single key K001 J029 T170 2413 Single key K001 J037 T148 2414 single key single key K001 J037 T170 2415 single key single key K001 J043 T148 2416 single key single key K001 J043 T170 2417 single key single key K001 J044 T148 2418 single key single key K001 J044 T170 2419 single key single key K001 J045 T148 2420 Single key K001 J045 T170 2421 Single key K001 J138 T148 2422 Single key K001 J138 T170 2423 Single key K001 J144 T148 2424 Single key K001 J144 T170 2425 Single key K002 J012 T148- 206- (202) 200526665 Compound No.-A1- -A2- -G1-A3-A4_G2 -As-R2 -As-R3 2426 Single bond single bond K002 J012 T170 2427 Single bond single bond K002 J044 T148 2428 Single bond single bond K002 J044 T170 2429 Single key K002 J045 T170 2430 Single key K002 J139 T148 2431 Single key K002 J139 T170 2432 Single key K197 J002 T148 2433 Single key K197 J002 T170 2434 Single key K197 J007 T148 2435 Single key K197 J007 T170 2436 Single key single key K197 J008 T148 2437 Single key single key K197 J008 T170 2438 Single key single key K197 J010 T148 2439 Single key single key K197 J010 T170 2440 Single key single key K197 J012 T170 2441 Single key single key K197 J013 T148 2442 Single key Single key K197 J013 T170 2443 Single key K197 J014 T148 2444 Single key K197 J014 T170 2445 Single key K197 J018 T148 2446 Single key K197 J022 T148 2447 Single key K197 J022 T170 2448 Single key K197 J026 T148 2449 Single bond single bond K197 J026 T170 2450 Single bond single bond K197 J027 T148 -207- 200526665 (203) Compound number -A1- -A2- -g, a3-a4-g2 -As-R2 -Ae-R3 2451 single key K197 J027 T170 2452 single key K197 J028 T148 2453 single key K197 J028 T170 2454 single key K197 J029 T148 2455 single key K197 J029 T169 2456 single Single key K197 J029 T170 2457 Single key K197 J030 T148 2458 Single key K197 J030 T170 2459 Single key K197 J031 T148 2460 Single key K197 J031 T170 2461 Single key K197 J032 T148 2462 Single key Single Key K197 J032 T170 2463 Single key Single key K197 J034 T148 2464 Single key Single key K197 J034 T170 2465 Single key Single key K197 J036 T148 2466 Single key Single key K197 J036 T170 2467 Single key Single key K197 J037 T148 2468 Single key Single key K197 J037 T170 2469 Single key single key K197 J039 T148 2470 Single key single key K197 J039 T170 2471 Single key single key K197 J043 T148 2472 Single key single key K197 J043 T170 2473 Single key single key K197 J044 T148 2474 Single key single key K197 J044 T170 2475 single bond K197 J045 T148 -208 · 200526665 (204) compound number -A1- -G, A3-A4-G2 -a5-r2 -A, R3 2476 single bond K197 J045 T170 2477 single bond K197 J090 T148 2478 Single key single key K197 J090 T170 2479 Single key single key K197 J092 T148 2480 Single key single key K197 J092 T170 2481 Single key single key K197 J144 T148 2482 Single key single key K197 J121 T148 2483 Single key K197 J121 T170 2484 Single key K197 J137 T148 2485 Single key K197 J137 T170 2486 Single key K197 J138 T148 2487 Single key K197 J138 T170 2488 Single key K197 J139 T148 2489 single key K197 J139 T170 2490 single key K197 J141 T148 2491 single key K197 J141 T170 2492 single key K197 J142 T148 2493 single key K197 J142 T169 2494 single key K197 J142 T170 2495 single Single key K197 J143 T148 2496 Single key K197 J143 T170 2497 Single key K197 J107 T148 2498 Single key K197 J144 T170 2499 Single key K223 J001 Ding 164 2500 Single key K223 J138 T148 -209- 200526665 (205) Compound No.-A1- -A2- -G1-A3-A Gas G2 • a5-r2 -a6-r3 2501-(CH2) 3--c (= o〉 -o · K002 J001 T001 2502 ** (CH2) 3- -C (= 0) -0 * K002 J001 T005 2503-(ch2) 3- -0 (= 〇) -〇- K197 J001 T148 2504-(CH2) 3. -0 (= 0) · 0- K002 J002 Ding 148 2505-(CH2) 3_ -C (= 0) -0- K197 J002 T170 2506-(CH2) 3- -C (= 0) -NH- K346 J002 T170 2507 _ (ch2) 3- • c (= o) _o · K002 J012 T001 2508-(CH2) 3- -0 (= 0) -0- K002 J012 T005 2509-(ch2) 3- -C (= 0) -0- K002 J012 T148 2510 • (ch2) 3- -0 (= Ο) -Ο- K002 J012 T170 2511-(CH2) 2 · -NH-C (= 0)-K005 J012 Ding 004 2512-(CH2): t -C (= 0) -0- K002 J001 T148 2513 &quot; (CH2) 2. -NH-C (= 0) -0- K005 J045 T181 2514-(CH2) 2- -NH-C (= 0)-K338 J012 T148 -210- 200526665 (206) and Among the compounds listed in Table 1, the compound with the lower number is the better compound number 1 9 2 0 \ 2 2 2 2 7 2 9 8 S 3 9 4 0 4 1 \ 4 2, 4 3, 4 4 \ 5 1 5 2 &gt; 5 3 5 4, 5 6, 5 7 \ 5 8 3, 6 4 6 6, 6 7, 6 8 6 9 \ 7 0 7 7 \ 7 8 \ 7 9-8 1 8 4 N 8 5 8 6 2 \ 9 3 V 9 4-9 5 \ 9 6 9 7 9 8 \ 3 V 1 0 4 1 0 5, 1 0 6 1 0 7 1 0 1 1 3, 1 1 4 1 1 5 1 1 6, 1 1 7 2 1 2 3 1 2 4% 1 2 5 V 1 2 6 1 2 1 3 2 \ 1 3 3 、 1 3 4 \ 1 3 5-1 3 6 、 1 1 4 2 1 4 3 \ 1 4 4 , 1 4 5 \ 1 4 0 3 4, 3 6 \ 3 7 3 4 7 \ 4 8 V 4 9 5 〇, 9 6 0 \ 6 1 Ν 6 2 6 7 2 7 3% 7 4 7 6, 7 \ 8 8 9 0, 9 1 &gt; 9 0 \ 1 0 1% 1 0 2 \ 1 0 1 1 0 1 1 1, 1 1 2 \ 8 Λ 1 2 0 1 2 1 1 2 1 2 8 1 3 0 \ 1 3 1, 7 \ 1 3 8 1 4 0% 1 4 14 7 1 4 8 1 5 0

-211-200526665 (207) 1 5 1 、 1 5 2 1 5 3 1 5 4 1 5 5 1 5 6 N 1 5 7 1 5 8 、 1 6 0 &gt; 1 6 1 1 6 2 X 1 6 3 、 1 6 4 1 6 5, 1 6 6 \ 1 6 7 1 6 8 V 1 7 0 \ 1 7 1 1 7 2 \ 1 7 3 1 7 4 1 7 5 1 7 6 1 7 7 1 7 8 1 8 0 1 8 1 1 8 2 1 8 3 、 1 8 4 1 8 5 1 8 6-1 8 7 \ 1 8 8 \ 1 9 0-1 9 1 、 1 9 2 N 1 9 3 \ 1 9 4 1 9 5 1 9 6 1 9 7 V 1 9 8 2 0 0, 2 0 1-2 0 2 2 0 3 \ 2 0 6 2 1 0 \ 2 1 1 2 1 3 N. 2 1 4 2 1 7 2 1 9 2 2 1% 2 2 3 \ 2 2 5% 2 2 6 2 2 7 Λ 2 2 8 &gt; 2 2 9 2 3 0 &gt; 2 3 1 2 3 2 2 3 7 2 4 0, 2 4 1 \ 2 4 2 2 4 3 &gt; 2 4 4 &gt; 2 4 5 2 5 0 &gt; 2 5 3 s 2 5 4 2 5 5 \ 2 5 7 2 5 8 V 2 6 0 2 6 1 2 6 2 2 6 3 、 2 6 5 2 6 6 &gt; 2 6 7 V 2 6 8, 2 6 9 V 2 7 5 2 7 6 2 7 7 2 7 8, 2 7 9 V 2 8 0 2 8 1 &gt; 2 8 2 \ 2 8 3% 2 8 4 2 8 5 \ 2 8 6 2 8 7 2 8 8 2 9 4 \ 2 9 5 \ 2 9 6 、 2 9 7 N 2 9 8 s 2 9 9 3 0 0 \ 3 0 1 3 0 2 \ 3 0 3 \ 3 0 8 3 0 9 &gt; 3 1 0, 3 1 1 3 1 2 \ 3 1 3 3 1 4, 3 1 5 V 3 1 6 '3 1 7 s 3 2 0 \ 3 2 1 3 2 7 \ 3 2 8 3 3 0 \ 3 3 1 N 3 3 2 \ 3 3 3 &gt; 3 3 4 \ 3 3 5 3 4 0 \ 3 4 2 s 3 4 3 \ 3 4 8 N 3 4 9 3 5 0 N 3 5 1 V 3 5 2, 3 5 3 3 5 9 3 6 1, 3 6 2 3 6 3 3 6 4 \ 3 6 5 N 3 6 6 V 3 6 8 3 6 9 \ 3 7 1 \ 3 7 3 3 7 9 \ 3 8 1 \ 3 8 2 3 8 3 、 3 8 4% 3 8 5 s 3 8 6 \ 3 8 7 、 3 9 2 N 3 9 3 3 9 5 3 9 7 \ 3 9 8 \ 3 9 9 V 4 0 0% 4 0 1 \ 4 0 7 4 0 9 N 4 1 0, 4 1 1 4 1 2, 4 1 3 \ 4 1 5 4 1 6 4 1 7-4 1 8 4 1 9 4 2 0 \ 4 2 1 4 2 2 \ 4 2 3 4 2 6 4 2 7 4 2 9% 4 3 0 V 4 3 1% 4 3 2 4 3 3 、 4 3 4 4 3 7 4 3 8 N 4 3 9 \ 4 4 5 、 4 4 7 4 4 S 4 4 9 \ 4 5 1 4 5 3 N 4 5 4 \ 4 5 5 、 4 5 6 \ 4 5 7 N 4 6 3 &gt; 4 6 5 \ 4 6 6 4 6 7 4 6 8 4 6 9 4 7 1 V 4 7 2 4 7 3 4 7 4 \ 4 7 5 4 7 6 N 4 7 7 \ 4 7 8 \ 4 7 9 \ 4 8 3 4 8 4 4 8 5 、 4 8 6 4 8 7 4 8 8 s 4 8 9 、 4 9 0 、 4 9 1-4 9 2 N 4 9 3 4 9 4 V 4 9 7 N 4 9 8 s 4 9 9 5 0 1 5 0 2, 5 0 3 \ 5 0 4 V 5 0 9 s 5 1 1, 5 1 2 N 5 1 3% 5 1 5 \ 5 1 7 5 1 8 5 1 9 \ 5 2 0 5 2

-212- 200526665 (208) 1 5 2 7% 5 2 9 \ 5 3 0 V 5 3 1, 5 3 2 \ 5 3 3 5 3 4, 5 3 5 \ 5 3 6 \ 5 3 7 V 5 3 9 5 4 0 5 4 1 Ν 5 4 3 X 5 4 4 \ 5 4 5 \ 5 4 6 5 4 7 V 5 4 8-5 4 9 \ 5 5 0 \ 5 5 1 &gt; 5 5 2 \ 5 5 5 5 5 6 \ 5 5 7-5 6 3 5 6 5 5 6 6-5 6 7 5 6 9 V 5 7 1 5 7 2 \ 5 7 3 5 7 4 5 7 5 5 8 1 \ 5 8 3 \ 5 8 4 \ 5 8 5 5 8 6 V 5 8 7 '5 8 9 5 9 0% 5 9 1 \ 5 9 3 V 5 9 4 \ 5 9 5, 5 9 6 ν 5 9 7 \ 5 9 9 6 0 0 6 0 1 \ 6 0 2 6 0 5 6 0 6 \ 6 0 7 6 0 8 6 1 0 \ 6 1 1 &gt; 6 1 2 \ 6 1 3 \ 6 1 5 N 6 1 6 \ 6 1 7 \ 6 1 8 6 2 0 \ 6 2 1 、 6 2 3 \ 6 2 4 6 2 5 \ 6 2 6 、 6 2 7 6 2 8 6 2 9 \ 6 3 0-6 3 1 6 3 4 、 6 3 5 , 6 3 8 6 3 9 \ 6 4 1 6 4 2, 6 4 3 \ 6 4 4 6 4 5 6 4 6 6 4 7 S 6 4 8 &gt; 6 5 1 β 5 2, 6 5 3 &gt; 6 5 5 &gt; 6 5 6, 6 5 7 6 5 8 \ 6 5 9 \ 6 6 0 \ 6 6 1 \ 6 6 2 6 6 3 6 6 4 6 6 5 6 6 6 6 6 7-6 6 8 6 6 9 6 7 0% 6 7 1 6 7 2 \ 6 7 3 &gt; 6 7 5 S 6 7 6 6 7 7 N 6 7 8, 6 7 9-6 8 α 6 8 2 \ 6 8 3 6 8 4 6 8 5 S 6 8 6 '6 δ 7 、 6 8 8 6 8 9 6 9 0 6 9 1 6 9 2 N 6 9 3% 6 9 4% 6 9 5 6 9 6 ν 6 9 7% 7 0 0 、 7 0 1, 7 0 2 \ 7 0 4, 7 0 5 7 0 6 \ 7 0 7, 7 0 9 \ 7 1 0 Ν 7 1 1 7 1 2 Ν 7 1 3 \ 7 1 5, 7 1 6 \ 7 1 7% 7 1 8 7 1 9 \ 7 2 1 7 2 2 7 2 3 \ 7 2 4 7 2 5 7 2 6 7 2 7, 7 2 8 Ν 7 2 9% 7 3 0 Λ 7 3 1 7 3 2 7 3 3 \ 7 3 4 V 7 3 5, 7 3 6 \ 7 3 7 7 3 8 \ 7 3 9, 7 4 0, 7 4 1, 7 4 3 7 4 4 N 7 4 5 Ν 7 4 7 7 4 8 Ν 7 4 9 \ 7 5 0 Ν 7 5 1 \ 7 5 2 S 7 5 3-7 5 4 \ 7 5 5 7 5 6 Ν 7 5 7 \ 7 5 8 7 5 9 &gt; 7 6 0 7 6 1 N 7 6 2 \ 7 6 3 \ 7 6 4% 7 6 5 \ 7 6 6 7 6 7 7 6 8, 7 6 9 \ 7 7 0 \ 7 7 1 &gt; 7 7 3 7 7 6 \ 7 mm 7 、 7 7 8 7 7 9 7 8 0 7 8 1 7 8 2 、 7 8 3 7 8 4 V 7 8 5 \ 7 8 6% 7 8 7 \ 7 8 8 \ 7 8 9 7 9 0 '7 9 1 \ 7 9 2 7 9 3 X 7 9 4 \ 7 9 5 V 7 9 6 8 0 1 8 0 2 8 0 2 \ 8 0 4 8 0 5 Λ 8 0 6, 8 0 7% 8 0 8 8 0 9 8 1 0 8 1 1 \ 8 1 2, 8 5 2 &gt; 8 5 3 \ 8 7 4 \ 8 9 2 Ν 8 9 3 9 1 5 \ 9 1 7 N 9 1 8 9 1 9 9 2 1 9 3 9% 9 4 6 9 9 8 • 213- 200526665 (209) 1 0 0 〇, 1 0 0 1 V 1 0 0 2, 1 0 0 7, 1 0 0 8, 1 0 1 4, 1 0 1 5, 1 0 5 4, 1 〇5 5, 1 0 5 6, 1 0 5 9, 1 0 6 1 X 1 0 6 3 s 1 0 6 5, 1 0 6 7, 1 0.6 9, 1 0 7 1, 1 0 7 3, 1 0 7 5, 1 0 7 6, 1 0 7 7, 1 0 7 8, 1 0 7 9, 1 0 8 〇, 1 0 8 1, 1 0 8 3, 1 0 8 5, 1 0 8 9. 1 0 9 0, 1 0 9 1, 1, 0 9 2, 1 0 9 3, 1 0 9 5, 1 0 9 6, 1 0 9 7, 1 0 9 8, 1 0 9 9, 1 1 0 3, 1 1 0 4, 1 1 0 6, 1 1 1 0, 1 1 1 2, 1 1 1 3, 1 1 1 5, 1, 1 1 7, 7, 1 1 1 8, 1 1 2 0, 1 1 2 1. 1 1 2 7, 1, 1 2 9, 9, 1 1 3 〇, 1 1 3 1 V 1 1 3 2, 1 1 3 4, 1 1 3 7, 1 1 4 〇, 1 1 4 3, 1 1 4 6, 1 1 5 1. 1 1 5 2, 1 1 5 3, 1 1 5 5, 1 1 5 6, 1 1 5 8, 1 1 5 9, 1 1 6 1. 1 1 6 5, 1 1 6 6, 1 1 6 7, 1 1 6 8, 1 1 7 0, 1 1 7 8, 1 1 8 1, 1 1 8 2, 1 1 8 3, 1 1 8 4, 1 1 8 5, 1 1 8 6, 1 1 8 7, 1 1 8 8, 1 1 8 9, 1 1 9 0, 1 1 9 1. 1 1 9 2, 1 1 9 3, 1 1 9 4, 1 1 9 5, 1 1 9 6, 1 1 9 7, 1 1 9 8, 1 1 9 9 ν 1 2 0 0, 1 2 0 1, 1 2 0 2, 1 2 0 3, 1 2 0 4, 1 2 0 5, 1 2 0 6, 1 2 0 7, 1 2 0 8, 1 2 0 9, 1 2 1 0, 1 2 1 1, 1 2 1 2, 1 2 1 3, 1 2 1 4, 1 2 1 5, 1 2 1 6, 1 2 1 7, 1 2 1 8, 1 2 1 9, 1 2 2 0, 1 2 2 1, 1 2 2 2, 1 2 2 3, 1 2 2 4, 1, 2 2 5, 1, 2 2 6, 1, 2 2 7, 1, 2 2 8, 1, 2 2 9, 1, 2 3 〇, 1 2 3 1 &gt; 1 2 3 2, 1 2 3 3, 1 2 3 4, 1, 2 3 5, 1, 2 3 6, 1, 2 3 7, 1, 2 3 8, 1, 2 3 9, 1, 2 4 0, 1 2 4 1, 1 2 4 2, 1 2 4 3, 1 2 4 4, 1 2 4 5, 1 2 4 6, 1 2 4 7, 1 2 4 8, 1 2 4 9, 1 2 5 〇, 1 2 5 1 V 1 2 5 2, 1 2 5 3, 1 2 5 4, 1 2 5 5, 1 2 5 6, 1 2 5 7, 1 2 5 8, 1 2 5 9. 1 2 6 0, 1 2 6 1 &gt; 1 2 6 2, 1 2 6 3 1 2 6 4 1 2 6 5 1 2 6 6. 1 2 6 8 1 2 6 9 1 2 7 0 1 2 7 1 1 2 7 2 1 2 7 3 1 2 7 4 1 2 7 5 1 2 7 6 1 2 7 7 1 2 7 8 1 2 7 9 1 2 8 0 1 2 8 1 1 2 8 2 1 2 8 3 1 2 84, 1 2 8 5, 1 2 8 6, 1 2 8 7, 1 2 8 8, 1 2 8 9, 1 2 9 1.. 1 2 9 2, 1 2 9 3, 1 2 9 4, 1 2 9 5, 1 2 9 6, 1 2 9 7, 1 2 9 8, 1 2 9 9, 1 3 0 0, 1 3 0 1.. 1 3 0 2, 1 3 0 3, 1 3 0 4, 1 3 0 5, 1 3 0 6, 1 3 0 Ί, 1 3 0 8, 1 3 0 9, 1 3 1 0, 1 3 1 1, 1 3 1 2, 1 3 1 3, -214- 200526665 (210) 1 3 1 4, 1 3 1 5, 1 3 1 6, 1 3 1 7, 1 3 1 S, 1 3 1 9, 1 3 2 0, 1 3 2 1, 1 3 2 2, 1 3 2 3, 1 3 2 4, 1 3 2 5, 1, 3 2 6, 1, 3 2 7, 1, 3 2 8, 1, 3 2 9, 1, 3 3 0, 1 3 3 1.1.1 3 3 2, 1 3 3 3, 1 3 3 4, 1 3 3 5, 1, 3 3 6, 1, 3 3 7, 7, 1 3 3 8, 1, 3 3 9 ν 1 3 4 〇, 1 3 4 1 X 1 3 4 2, 1 3 4 3, 1 3 4 4, 1 3 4 5, 1 3 4 6, 1 3 4 7, 1 3 4 8, 1 3 4 9, 1 3 5 0, 1 3 5 1 &gt; 1 3 5 2, 1 3 5 3 1 3 5 4, 1 3 5 5, 1 3 5 6, 1 3 5 Ί, 1 3 5 8, 1 3 5 9, 1 3 6 0, 1 3 6 1, 1 3 6 2, 1 3 6 3 1 3 6 4, 1 3 6 5, 1 3 6 6, 1 3 6 7, 1 3 6 8, 1 3 6 9s 1 3 7 〇, 1 3 7 1 V 1 3 7 2, 1 3 7 3, 1 3 7 4, 1, 3 7 5, 1, 3 7 6, 1 3 7 7, 1 3 7 8, 1 3 7 9, 1 3 8 〇s 1 3 8 1. 1 3 8 2, 1 3 8 3, 1 3 8 4, 1 3 8 5, 1, 3 8 6, 1, 3 8 Ί, 1 3 8 8, 1 3 8 9, 1 3 9 Ον 1 3 9 1, 1 3 9 2, 1 3 9 3, 1 3 9 4, 1 3 9 5, 1 3 9 6, 1 3 9 7, 1 3 9 8, 1 3 9 9, 1 4 0 0, 1 4 0 1, 1 4 0 2, 1 4 0 3, 1 4 0 4, 1, 4 0 5, 1, 4 0 6, 1, 4 0 7, 1, 4 0 8, 1, 4 0 9, 1, 4 1 0, 1 4 1 1, 1 4 1 2, 1 4 1 3, 1 4 1 4, 1 4 1 5, 1 4 1 6, 1 4 1 7, 1 4 1 8, 1 4 1 9 '1 4 2 0, 1 4 2 1, 1 4 2 2, 1 4 2 3, 1 4 2 4, 1 4 2 5, 1 4 2 6, 1 4 2 7, 1 4 2 8, 1 4 2 9, 1 4 3 0, 1 4 3 1, 1 4 3 2, 1 4 3 3.Ί 4 3 4, 1, 4 3 5, 1, 4 3 6, 1, 4 3 7, 7, 4 3 8, 1, 4 3 9, 1, 4 4 〇, 1 4 4 1, 1, 4 4 2, 1 4 4 3, 1 4 4 4, 1 4 4 5, 1 4 4 6, 1 4 4 7, 1 4 4 8, 1 4 4 9, 1 4 5 0, 1 4 δ 1, 1 4 5 2, 1 4 5 3, 1 4 5 4, 1 4 5 5, 1 4 5 6, 1 4 5 7, 1 4 5 8, 1 4 5 9, 1 4 6 〇, 1 4 6 1 s 1 4 6 2 1 4 6 3, 1 4 6 4, 1, 4 6 5, 1, 4 6 6, 1 4 6 Ί, 1 4 6 8, 1 4 6 9, 1 4 7 0, 1 4 7 1, 1 4 7 2, 1 4 7 3, 1 4 7 4, 1, 4 7 5, 1, 4 7 6, 1 4 7 7, 1 4 7 8, 1 4 7 9, 1 4 8 〇, 1 4 8 Is 1 4 8 2, 1 4 8 3, 1 4 8 4, 1, 4 8 5, 1, 4 8 6, 1, 4 8 7, 1, 4 8 8, 1 4 8 9, 1 4 9 0, 1 4 9 1 &gt; 1 4 9 2, 1 4 9 3, 1 4 9 4, 1, 4 9 5, 1, 4 9 6, 1 4 9 7, 1 4 9 8, 1 4 9 9, 1 5 0 0, 1 5 0 1, 1 5 0 2, 1 5 0 3, 1 5 0 4, 1 5 0 5, 1 5 0 6, 1 5 0 7, 1 5 0 8, 1 5 0 9, 1 5 1 0, 1 5 1 1, 1 5 1 2, 1 5 1 3, 1 5 1 4, 1, 5 1 5, 1, 5 1 6,

• 215- 200526665 (211) 15 17, 1 5 2 4, 15 3 1, 1 5 3 8, 1 5 4 5, 1 5 5 2, 1 5 5 9, 1 5 6 6, 1 5 7 3, 1 5 8 0, 1 5 8 7, 1 5 9 4, 16 0 1, 1, 6 0 8, 16 15, 1 6 2 2, 1 6 2 9, 1 6 3 6. 1 6 4 3, 1 6 5 0 , 1 6 5 7, 16 6 4, 16 7 1, 1 6 7 8, 1 6 8 5, 1 6 9 2, 1 7 0 0, 1 7 0 7, 17 14s 15 18, 1 5 2 5, 1 5 3 2, 1 5 3 9, 1 5 4 6, 1 5 5 3, 1 5 6 0, 1 5 6 7, 1 5 7 4, 15 8 1, 1 5 8 8, 1 5 9 5, 1 6 0 2, 1 6 0 9, 16 16, 1 6 2 3, 1 6 3 0, 16 3 7, 1 6 4 4, 16 5 1, 1, 6 5 8, 1 6 6 5, 1 6 7 2, 1 6 7 9, 1 6 8 6, 1 6 9 3, 17 0 1, 1, 7 0 8 s 17 15. 15 19, 1 5 2 6, 1 5 3 3, 1 5 4 0, 1 5 4 7, 1 5 5 4, 15 6 1, 1 5 6 8 x 1 5 7 5, 1 5 8 2 N 1 5 8 9, 1 5 9 6, 1 6 0 3, 16 10, 1 6 1 7 \ 1 6 2 4 , 16 3 1, 1 6 3 8. 1 6 4 5, 1 6 5 2, 1 6 5 9 N 1 6 6 6, 1 6 7 3, 1 6 8 0, 1 6 8 7, 16 9 4, 1 7 0 2, 1 7 0 · 9, 17 16, 1 5 2 0, 1 5 2 7, 1 5 3 4, 15 4 1, 1 5 4 8, 1 5 5 5 1 5 6 2, 1 5 6 9, 1 5 7 6, 1 5 8 3, 1 5 9 0, 1 5 9 7, 1 6 0 4, 16 11, 16 18, 1 6 2 5, 1 6 3 2 , 1 6 3 9, 1 6 4 6, 1 6 5 3, 1 6 6 0, 1 6 6 7, 16 7 4, 16 8 1, 1 6 8 8, 1 6 9 5, 1 7 0 3, 17 10, 17 17, 15 2 1, 1 5 2 8, 1 5 3 5, 1 5 4 2, 1 5 4 9, 1 5 5 6, 1 5 6 3, 1 5 7 0, 1 5 7 7, 1 5 8 4, 15 9 1, 1, 5 9 8, 1, 6 0 5, 16 12, 16 19, 1 6 2 6, 1 6 3 3, 16 4 0, 1 6 4 7, 1 6 5 4, 16 6 1, 1 6 6 8, 1, 6 7 5, 1, 6 8 2, 1 6 8 9, 1 6 9 6, 1 7 0 4, 17 11, 17 18, 1522, 1523, 1529, 1530, 1 5 3 6 , 1 5 3 7, 1543, 1544, 1550, 1551, 1 5 5 7, 1 5 5 8, 1564, 1 5 6 5. 15 7 1, 1 5 7 2, 1 5 7 8, 1 5 7 9, 1 5 8 5, 1586, 1592, 1593, 1599, 1600, 1606, 1607, 1613, 1614, 1620, 1621, 1627, 1628, 1634, 1635, 1641, 1642, 1648, 1649, 1655, 1656, 1662, 1663 , 1669, 1 6 7 0, 1676, 1677, 1683, 1684, 1690, 1691, 1697, 1698, 1705, 1706, 17 12, 1713 1719,1720,

-216 · 200526665 (212) 1721, 1722, 1723, 1728, 1729, 1730, 1735, 1736, 1737, 1742, 1743, 1 744, 1749, 1750, 17 51, 1756, 1 7 5 7 N 1 7 5 8 . 1763, 1764, 1765, 1770, 1771, 1772, 1777, 17 7 8, 1779, 1784, 1785, 1 7 8 6. 1791, 1 7 9 2. 1793, 1798, 1799, 1 800, 1805, 1806, 180 7, 1812, 1813, 18 14, 1819, 1820, 18 21, 1826, 1827, 1829, 1834, 1835, 1836, 1841, 1842, 1843, 1848, 1849, 1850, 1855, 1856, 1857, 1862, 1863 , 1864, 1869, 1870, 1 8 7 1 v 1876, 1877, 1878, 1883, 1884, 1885, 1890, 1891, 1892, 1897, 1898, 1899, 1904, 1905, 1906, 1911, 19 12, 1913, 1918 , 1919, 1920, 724, 1725, 1726, 1727, 731, 1732, 1733, 1734, 738, 1739, 1740, 1741, 745, 1746, 1747, 1748, 752, 1753, 1754, 1755, 759, 1760, 1761 , 1762, 766, 1767, 1768, 1769, 773, 1774, 1775, 1776, 780, 1781, 1782, 1783, 787, 1788, 1789, 1790, 794, 1795, 1796, 1797, 801, 1802 1803, 1804, 808, 1809, 1810, 1811, 815, 1816, 1817, 1818, 822, 1823, 1824, 1825, 830, 1831, 1832, 1833, 837, 1838, 1839, 1840, 844, 1845, 1846, 1847, 851, 1852, 1853, 1854, 858, 1859, 1860, 1861, 865, 1866, 1867, 1868, 872, 1873, 1874, 1875, 879, 1880, 1881, 1882, 886, 1887, 1888, 1889, 893, 1894, 1895, 1896, 900, 1901, 1902, 1903, 907, 1908, 1909, 1910, 914, 1915, 1916, .1917, 921, 1922, 1923, 1924, 200526665 (213) 1 9 2 5, 1 9 3 2, 1 9 3 9, 1 9 4 6, 1 9 5 3, 1 9 6 0, 1 9 6 7, 1 9 7 4, 19 8 1, 1 9 8 8, 1 9 9 5, 2 0 0 2, 2 0 10, 2 0 17, 2 0 2 4, 2 0 3 1, 2 0 3 8, 2 0 4 5, 2 0 5 2, 2 0 5 9, 2 0 6 6, 2 0 7 3, 2 0 8 0, 2 0 8 7, 2 0 9 4, 2 10 1, 2 10 8, 2 116, 2 12 4, 1 9 2 6, 1 9 3 3, 1 9 4 0, 1 9 4 7, 1 9 5 4, 19 6 1, 1 9 6 8, 1 9 7 5, 1 9 8 2, 1 9 8 9, 1 9 9 6, 2 0 0 3. 2 0 11, 2 0 18, 2 0 2 5, 2 0 3 2, 2 0 3 9 , 2 0 4 6, 2 0 5 3, 2 0 6 0, 2 0 6 7, 2 0 7 4, 2 0 8 1, 2 0 8 8, 2 0 9 5, 2 10 2, 2 10 9, 2, 117, 2 12 5, 1 9 2 7, 1 9 3 4, 19 4 1, 1 9 4 8, 1 9 5 5, 1 9 6 2, 1 9 6 9, 1 9 7 6, 1 9 8 3 \ 1 9 9 0, 1 9 9 7, 2 0 0 4, 2 0 12, 2 0 19, 2 0 2 6, 2 0 3 3, 2 0 4 0, 2 0 4 7, 2 0 5 4, 2 0 6 1, 2, 0 6 8, 2, 0 7 5, 2, 0 8 2, 2 0 8 9, 2, 0 9 6. 2 10 3, 2 111, 2 118, 2 12 8, 1 9 2 8, 1 9 3 5, 1 9 4 2, 1 9 4 9, 1 9 5 6, 1 9 6 3, 1 9 7 0, 1 9 7 7 '1 9 8 4, 19 9 1, 1 9 9 8 v 2 0 0 5 , 2 0 13, 2 0 2 0% 2 0 2 7, 2 0 3 4, 2 0 4 1, 2 0 4 8, 2 0 5 5, 2 0 6 2, 2 0 6 9, 2 0 7 6, 2 0 8 3, 2 0 9 0, 2 0 9 7, 2 10 4, 2 112, 2 119, 2 12 9, 1 9 2 9, 1 9 3 6, 1 9 4 3, 1 9 5 0, 1 9 5 7, 1 9 6 4, 19 7 1, 1, 9 7 8 N 1 9 8 5 \ 1 9 9 2, 1 9 9 9, 2 0 0 6, 2 0 14, 2 0 2 1, 2 0 2 8, 2 0 3 5, 2 0 4 2, 2 0 4 9, 2 0 5 6, 2 0 6 3, 2 0 7 0, 2 0 7 7, 2 0 8 4, 2 0 9 1, 2 0 9 8, 2 10 5, 2 113. 2 12 1, 2 13 0, 1 9 3 0, 1 9 3 7, 1 9 4 4, 19 5 1. 1 9 5 8, 1 9 6 5 , 1 9 7 2. 1 9 7 9, 1 9 8 6, 1 9 9 3, 2 0 0 0, 2 0 0 7, 2 0 15, 2 0 2 2, 2 0 2 9, 2 0 3 6. 2 0 4 3, 2 0 5 0, 2 0 5 7, 2 0 6 4, 2 0 7 1, 2 0 7 8, 2 0 8 5, 2 0 9 2. 2 0 9 9, 2 10 6, 2 114, 2 12 2n 2 13 1, 19 3 1, 1 9 3 8, 1 9 4 5, 1 9 5 2, 1 9 5 9, 1 9 6 6. 1 9 7 3, 1 9 8 0, 1 9 8 7, 1 9 9 4 s 2 0 0 1. 1.2 0 0 8, 2 0 16, 2 0 2 3, 2 0 3 0, 2 0 3 7, 2 0 4 4. 2 0 5 1, 2 0 5 8, 2 0 6 5, 2 0 7 2, 2 0 7 9, 2 0 8 6, 2 0 9 3, 2 10 0, 2 10 7, 2 115, 2 12 3, 2 13 2, -218- 200526665 (214) 2 1 3 3, 2 1 3 4, 2 1 3 5, 2 1 2 1 4 0, 2 1 4 3, 2 1 4 4, 2 1 2 1 4 9, 2 1 5 0, 2 1 5 1, 2 1 2 1 5 6, 2 1 5 7, 2 1 5 8, 2 1 2 1 6 3, 2 1 6 4, 2 1 6 6, 2 1 2 1 7 1, 2 1 7 2, 2 1 7 3, 2 1 2 1 7 8, 2 1 7 9, 2 1 8 0, 2 1 2 1 8 5, 2 1 8 6, 2 1 8 7, 2 1 2 1 9 2, 2 1 9 3, 2 1 9 4, 2 1 2 1 9 9, 2 2 0 0, 2 2 0 1, 2 2 2 2 0 6, 2 2 0 7, 2 2 0 8, 2 2 2 2 1 3 , 2 2 1 4, 2, 2 1 5, 5, 2 2 2 2 2 0, 2 2 2 1, 2, 2 2 2, 2, 2 2 2 2 2 7, 2, 2 2 8, 8, 2 2 2 9, 2, 2 2 2 2 3 4, 2 2 3 5, 2, 2 3 6, 6, 2 2 2 2 4 1 &gt; 2 2 4 2, 2 2 4 3, 2 2 2 2 4 8, 2 2 4 9, 2 2 5 0, 2 2 2 2 5 5, 2 2 5 6, 2, 2 5 7, 7, 2 2 2 2 6 2, 2 2 6 3, 2 2 6 4, 2 2 2 2 6 9, 2, 2 7 0, 2 2 7 1 V 2 2 2 2 7 6, 2 2 7 Ί, 2 2 7 8, 2 2 2 2 8 3, 2 2 8 4, 2 2 8 5, 2, 2 2 2 9 1 &gt; 2 2 9 2, 2 2 9 3 2 2 2 2 9 8, 2 2 9 9, 2 3 0 Ον 2 3 2 3 0 6, 2 3 0 Ί, 2 3 0 8, 2 3 2 3 1 3, 2 ο 1 4, 2 3 1 5, 2 3 2 3 2 0, 2 3 2 1, 2, 3 2 2, 2 3 2 3 2 7, 2, 3 3 8, 8, 2 3 2 9, 2, 3 2 3 3 4, 4, 2 3 3 5, 2, 3 3 6 2 3 6 2 1 3 7 2 1 3 8 2 1 3 9 5 2 1 4 6 2 1 4 7 2 1 4 8 2 2 1 5 3 2 1 5 4 2 1 5 5 s 9, 2 1 6 0, 2 1 6 1 V 2 1 6 2, 7, 2 1 6 8, 2 1 6 9, 2 1 7 〇 &gt; 4, 2 1 7 5 , 2 1 7 6, 2 1 7 7, 1, 2 1 8 2, 2 1 8 3, 2 1 8 4, 8, 2 1 8 9, 2 1 9 0, 2 1 9 1, 5, 2 1 9 6, 2 1 9 7, 2 1 9 8, 2, 2 2 0 3, 2 2 0 4, 2 2 0 5, 9, 2 2 1 0, 2 2 1 1 S 2 2 1 2, 6, 2 2 1 Ί, 2 2 1 8, 2 2 1 9, 3, 2 2 2 4, 2, 2 2 2 5, 2 2 2 6, 0, 2 2 3 1, 2 2 3 2, 2 2 3 3, 7, 2 2 3 8, 2, 2 3 9, 9, 2 2 4 0, 4, 2 2 4 5, 2, 2 4 6, 2, 2 4 7, 1, 2, 2 2 5, 2, 2 2 5 3, 2 2 5 4, 8 ,, 2 2 5 9. 2 2 6 0, 2 2 6 1, 5, 2 2 6 6, 2 2 6 7, 2 2 6 8, 2, 2 2 7 3, 2 2 7 4, 2 2 7 5, 9 , 2 2 8 0, 2 2 8 1, 2 2 8 2, 6, 2 2 8 8, 2 2 8 9, 2 2 9 0, 4, 2 2 9 5, 2 2 9 6, 2 2 9 7, 2, 2 3 0 3, 2 3 0 4, 2 3 0 5, 9, 2 3 1 〇, 2 3 1 1, 2 3 1 2, 6, 2 3 1 7, 2 3 1 8, 2 3 1 9 , 3, 2 3 2 4, 2, 3 2 5, 5, 2 3 2 6, 0, 2 3 3 1, 2 3 3 2, 2 3 3 3, 7, 2 3 3 8, 2, 3 3 9, 9, 2 3 4 0, -219- 200526665 (215) 2341, 2342, 2343, 2 348, 2349, 2350, 2355, 2356, 2357, 2363, 236 4, 2365, 2370, 2371, 2372, 2377, 2378, 2379, 238 4, 2385, 2386, 2391, 2392, 2393, 2398, 2 399, 2400, 2405, 2406, 2407, 2412 , 2413, 2414, 2419, 2420, 2421, 2426, 2427, 2428, 2434, 2435, 2436, 2441, 2442, 2443, 2 4 4 8, 2449, 2450, 2455, 2456, 2457, 2462, 2 463, 2464 , 2469, 2470, 2471, 2476, 2477, 2478, 2483, 2484, 2485, 2490, 2491, 2492, 2497, 2498, 25 0 5, 2344, 2.345, 2 3 4 2351, 2352, 2 3 5 2 3 5 8, 2359, 236 2366, 2367, 2 3 6 2373, 2374, 2 3 7 2380, 2381, 238 2387, 2388, 2 3 8 2 3 9 4, 2395, 239 2401, 2402, 2 4 0 2408, 2409, 2 4 1 2415, 2416, 2 4 1 2422, 2423, 2 4 2 2429, 2430, 2 4 3 2437, 2438, 2 4 3 2444, 2445, 2 4 4 2451, 2452, 2 4 5 2458, 2459, 2 4 6 2465, 2466, 2 4 6 2472, 2473, 2 4 7 2479, 2480, 2 4 8 2486, 2487, 2 4 8 2 4 9 3, 2494, 249 2506, 2509, 2 5 1 6, 2 3 4 7, 3, 2 3 5 4, 0, 2 3 6 1, 8, 2 3 6 9, 5, 2 3 7 6 , 2, 2 3 8 3, 9, 2 3 9 0, 6, 2 3 9 7, 3, 2 4 0 4, 0, 2 4 11s φ 7, 2 4 18, 4, 2 4 2 5, 1, 1, 2 4 3 3, 9, 2 4 4 0, 6, 2 4 4 7, 3, 2 4 5 4, 0, 2 4 6 1, 7, 2 4 6 8, 4, 2 4 7 5, 8, 2 4 S 9,

5, 2 4 9 6, 0, 2 5 14 Although the above formula (I) is mentioned here, A], A2, G1, A3, A4, and G2 are better combinations, but they can be summarized as follows (1 ) To (4 1). Not only can these combinations be represented by a better mutual relationship of A1, A2, G1, A3, A4, and G2, the partial structures formed by them as a whole can also become the preferred substituents in the pyrimidone derivatives of the present invention. . -220- 200526665 (216) (1) In the above formula (I), A1 is _ (CH2) 2 ... and α1 · α2 · G1 is a combination of A ^ NH-C (= 0) -G1, and g1 When it is a phenyl group, the phenyl group of the G1 is substituted with ~ or more of the substituted C6 ~ c selected from the above 〇1 "Cyclo nicotinyl substituents as shown in the preferred examples of substituents as Preferably, (1) In the above formula (1), A1 is _ (CH2) 2 ·, aA ^ A2_Gl is bound as A -NH-C (= 0) -G1, and 〇1 is phenylene, and When the extended base of G1 is unsubstituted, it is preferable that the entirety of A, A, and G2 is a base other than a hydrogen atom. (3) In the formula (I), A1 is · ((: Η2) 2 ... and Aι · Α2-〇1 is bound in the form of A ^ NH-CM ^ O) -G1, and G! Is a ring having 1 to 3, preferably 2 atoms selected from oxygen, nitrogen, and sulfur atoms The monocyclic or bicyclic 2c3 ~ C9 aromatic heterocyclic divalent group of the formed atomic group is suitable. (4) In the formula (I), A1 is-(ch2) 2 ... and A ^ A ^ G1 is When combined in the form of Α, ΝΗ-(: (= 〇) -G1, g1 is 1 ~ 3 'in the ring, preferably! ~ 2 selected from the group consisting of oxygen atom, nitrogen atom, and sulfur atom. The monovalent or bicyclic C2 ~ C9 aromatic heterocyclic divalent group of the group, except that the divalent group of the aromatic heterocyclic ring of G 1 has 1 to 4 in the ring substituted by one or more of the above 〇1. The substituents in the preferred examples of the fluorenyl group of the heterocyclic group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom are more preferably substituted. (5) A1 in the above formula (I) is _ (CH2 ) 2-, and A ^ AlG1 is combined in the form of A] -NH-C (= 0) -G], and g] is 1 to 3 in the ring, preferably 1 to 2 is selected from Oxygen atom, nitrogen atom, and sulfur atom -221 · 200526665 (217) The atomic group formed by the monocyclic or bicyclic c2 ~ c9 aromatic heterocyclic divalent group is suitable, but the aromatic group of G1 When the divalent group of the heterocyclic ring is not substituted, it is preferable that the entire A3_A4-G2 system is a group other than a hydrogen atom. (6) In the formula (I), A1 is-(CH2) 2-, and ALA \ Gl is When combined in the form of eight 1- &gt; 111-0: (= 〇) -〇], and (}) is a single bond, the eight 3-A4-G2 system is a C! ~ C6 acyclic aliphatic hydrocarbon group as a whole, or A cycloalkylalkyl group formed from a CrQ acyclic aliphatic hydrocarbon group and a C3 to C8 alicyclic hydrocarbon group is preferable. (7) The above In formula (I), A1 is-(CH2) 2-, and A] -A2_g1 is combined as A, NΗ · (: (= 〇) -G1, and when G1 is a single bond, a3_ A4-G2 is a whole. It is C ^ C: 6 non-cyclic aliphatic hydrocarbon group, or a cycloalkylalkyl group formed by acyclic aliphatic hydrocarbon group and C3 ~ C8 alicyclic hydrocarbon group, but the C ^ of A3-A4-G2 The C: 6 acyclic aliphatic hydrocarbon group is preferably a substituent as shown in a preferred example of a substituent selected from the above-mentioned A3 substituted acyclic aliphatic hydrocarbon group. The A3-A4-G2 CrQ acyclic aliphatic hydrocarbon group and the C3 ~ C8 alicyclic hydrocarbon group are formed by more than one cycloalkylalkyl group, and the CrG acyclic aliphatic hydrocarbon group portion is shown by A3. The C3 ~ C1G alicyclic hydrocarbon group which is substituted by the selected substituent shown in the best examples of substituents or the C3 ~ C8 alicyclic hydrocarbon group is substituted by the above G3 One or more substituents are best substituted (including those in which both are substituted). (8) When A1 is-(CH2) 2- in the above formula (I), and A〗 -A2.gi is combined as A] -NH-C (= 0) -G1, and G1 is a single bond, The eight 3-A4-G2 series is preferably an aralkyl group formed by a C! ~ C6 acyclic aliphatic hydrocarbon group and a C6 ~ C10 aromatic hydrocarbon group. • 222- 200526665 (218) (9) When A] in the above formula (I) is-((: Η2) 2-, and A ^ A ^ G1 is g-formed in the form of _Gi, and g1 is a single bond, The whole of A3-A4-G2 is C] ~ C6 Acyclic alkyl formed by acyclic aliphatic hydrocarbon group and c6 ~ CI () aromatic hydrocarbon group is suitable, but the aralkyl system of A and A4-G2 is best Ci ~ C6 acyclic aliphatic hydrocarbon group part is one or more selected from the above-mentioned examples of preferred substituents of Ci ~ C 丨 0 acyclic aliphatic hydrocarbon group substituted by a3, or C6 ~ C1G aromatic hydrocarbon group One or more of the C6 ~ C14 aromatic hydrocarbon groups substituted with the above-mentioned examples are preferably substituted (including substitution of both). (10) A1 in the above formula (I) Is-(CH2) 2-, and A] -A2-G] is bonded in the form of A ^ NH-C (= 0) -G1. When G1 is a single bond, the A3-A4-G2 system is CrQ acyclic as a whole. A heterocyclic substituted alkyl group formed by an aliphatic hydrocarbon group of the formula and a heterocyclic group having 1 to 4 atoms selected from an oxygen atom, a nitrogen atom, and a sulfur atom in the ring. (11) A1 in the above formula (I) is -(CH2) 2-, and A ^ A ^ G1 is combined in the form of A, NH-C (= 0) -G], when G1 is a single bond A3-A4-G2 is a heterocyclic group substituted alkyl group formed by an acyclic aliphatic hydrocarbon group and a heterocyclic group having 1 to 4 atoms selected from oxygen, nitrogen, and sulfur atoms in the ring. However, the heterocyclic-substituted alkyl-based acyclic aliphatic hydrocarbon group portion of the A3-A4-G2 is substituted with one or more selected from among the preferred examples of the acyclic aliphatic hydrocarbon group substituted with the above-mentioned A3. A heterocyclic group substituted by a radical, or a heterocyclyl moiety containing a G2 substituted ring having 1 to 4 atomic groups selected from an oxygen atom, a nitrogen atom, and a sulfur atom, is shown as a preferred example. One or more of the selected substituents are substituted by -223- 200526665 (219) is the best (including the case where both are substituted). (12) In the above formula (I), A1 is-(CH2) 2_, and A ^ Α2-G1 is bonded in the form of A'NH-CC ^ O) _ΝΗ_αι, and when g1 is a phenyl group, the phenyl group of G1 is substituted with one or more C 6 ~ C μ aromatics selected from the above ^ The substituents of the group hydrocarbon group are preferably substituted by the substituents shown in the preferred examples. (13) The above formula (D in V is-(ch2) r, and Ai-A'G1 is bound as A ^ NH-C (= 0) -NH-G1, and G] is phenylene, and When the phenyl group of G1 is unsubstituted, it is preferable that the whole of A and a4_G2 is a group other than a hydrogen atom. (14) In the formula (I), A1 is-(CH2) 2-, and A ^ A ^ G1 It is combined in the form of A ^ NH-C (= 0) -NH-G1, and G] is a ring. There are 1 to 3, preferably 1 to 2 selected from the group consisting of an oxygen atom, a nitrogen atom, and The monovalent or bicyclic C3 ~ C9 aromatic heterocyclic bicyclic group of the atomic group formed by the sulfur atom is suitable. (15) In the formula (I), A1 is-(CH2) 2-, and A ^ AlG1 is bonded in the form of A, NH-C (= 0) -NH-G1, and Gi is 1 to 3 in the ring, preferably 1 to 2 selected from oxygen, nitrogen and sulfur The monovalent or bicyclic C2 ~ C9 aromatic heterocyclic divalent group of the atomic group formed by the atoms is suitable, but the divalent group of the aromatic heterocyclic ring of G1 is contained in the ring substituted by G1 The substituent of the heterocyclic group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom is preferably substituted with one or more of the substituents shown in the preferred examples. 2 'And A1 -A'G1 (16) in the above formula (I), A1 is-(CH2) -224- 200526665 (220) is bound as A ^ NH-C (= 〇) -NH-G1, and G There are 1 to 3, preferably 1 to 2 monocyclic or bicyclic C2 ~ ^ aromatic divalent groups selected from the group consisting of oxygen atoms and nitrogen atoms, but the aromatic group of G1 is suitable. As the divalent group of the heterocyclic ring, A3-A4-G2 is preferably a group other than a hydrogen atom. (17) In the formula (I), A1 is-(CH2) 2 · and Ai-NH-CC is used. ^ O) -NH-G1 is combined, and G] A, A4_G2 is preferably a cycloalkylalkyl group formed by Cl ~ C6 acyclic aliphatic hydrocarbon group | formula hydrocarbon group. (18) In the above formula (I), A1 is-(CH2) 2-, which is a combination of A] -NH-C (= 〇) -NH-G1, and G] A3-A4-G2 as a whole Cl ~ C6 acyclic aliphatic hydrocarbon group | A cycloalkylalkyl group formed by a formula hydrocarbon group is preferred, but the a3-a4-g2 system C ^ C: 6 acyclic aliphatic hydrocarbon group part is negated by the above A3 As shown in the preferred examples of the substituents of the cyclic aliphatic hydrocarbon group, the selected substituents are substituted, or the C3 ~ C1 () alicyclic hydrocarbon groups are substituted by the preferred examples of the C3 ~ C1 (alicyclic hydrocarbon group). It is best to be substituted by the selected substituent (including both being substituted (19). In the above formula (I), A1 is-(CH2) 2-, and A1-NΗ &lt; (= 〇) -NH-G1 It is preferred that G1 A -A -G2 is an aralkyl group formed by Ci ~ C6 acyclic aliphatic hydrocarbon group and family hydrocarbon group as a whole. (20) A1 in the above formula (I) is-(CH2) 2 -, When bonded in the form of V-NH, C (= 〇) -NH-G1, and G1 1 is an atom in the ring, and an unsubstituted thioaromatic heterocyclic ring, and 8 1 · ^ 2々 is In the case of a single bond, when C 3 to C 8 are alicyclic and A ^ A ^ G1 is a single bond, one of I C3 to C8 alicyclic cycloalkylalkylated C 1 to C 1 〇 Said G2, the kind of the substituent) ° and Α ^ Α2 :. When 1 is a single bond, C6 ~ C1Q is aromatic and A] -A2-G] is a single bond, -225 · 200526665 (221) Eight 3-six 4-02 series is [1 ~ 〇6 acyclic aliphatic The aralkyl group formed by the hydrocarbon group and (:: 6 ~ (: 1 () aromatic hydrocarbon group is suitable, but the aralkyl group of the A3-A4-G2 is preferably C) ~ C0 acyclic aliphatic hydrocarbon group portion One or more substitutions selected from the above-mentioned examples of preferred substituents of C3 ~ Cio acyclic aliphatic hydrocarbon groups substituted by A3, or C6 ~ Cl4 substituted by C6 ~ C1G aromatic hydrocarbon groups One or more selected from the examples of preferred substituents for aromatic nicotyl are substituted (including substitution of both). (21) A1 in the above formula (I) is-(CH2) 2-, and A ^ A ^ G1 is combined as A ^ NH-Ci ^ O) -NH-G1. When G1 is a single bond, the A3-A4-G2 system as a whole is &lt; ^ ~ (: 6 acyclic aliphatic hydrocarbon group and The ring has 1 to 4 heterocyclic substituted alkyl groups formed by a heterocyclic group selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. (22) A in the above formula (I) is _ (CH2) 2-, and A ^ A ^ G1 is bound as A ^ NH-CC ^ O) -NH-G1, when G] is a single bond, A3-A4- The G2 system as a whole is a Ci ~ C6 acyclic aliphatic hydrocarbon group, and a heterocyclic group substituted alkyl group formed with a heterocyclic group having 1 to 4 atoms selected from oxygen, nitrogen, and sulfur atoms in the ring, However, the A3-A4-G2 heterocyclic-substituted alkyl group c! ~ C6 acyclic aliphatic hydrocarbon group is substituted by Ci ~ Cl () acyclic aliphatic hydrocarbon group substituted by the above A3. One or more of the substituents selected by the shown are substituted by a heterocyclic group or a heterocyclic group containing 1 to 4 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. Cyclic substituents are preferably substituted by one or more of the substituents shown in the preferred examples (including when both are substituted). (23) In the above formula (I), A] is-(CH2) 2_ And α] · Α2 · (24) the above formula (I) and G 1 is a phenyl group, and • G 2 as a whole is a hydrogen atom 200526665 (222) G] is bonded in the form of V-NH-G], and When phenylene is phenylene, phenylene is substituted with one or more of the substituents selected from the above-mentioned substituents as shown in the preferred example of 帛. Yi! A! Is ((CH2)), and It is preferably bonded in the form of A ^ NH-G1, and the phenyl group is unsubstituted. (25) A ^-(CH2) 2 in the above formula (I) is bonded in the form of A-NH_G, and When 1 is a divalent monovalent C2 to C9 aromatic heterocyclic ring having an atomic group consisting of an i oxygen atom, a nitrogen atom, and a sulfur atom in the ring, the aromatic heterocyclic ring is the above-mentioned G-substituted ring In the preferred examples of the fluorenyl group having 1 to 4 heterocyclic groups selected from an oxygen atom and a sulfur atom group, the substitution is more preferable. (26) In the above formula (I), A1 is-(CH2) 2 · and is bonded in the form of A ^ NH-G1, and G] is formed by having 1 oxygen atom, nitrogen atom, and sulfur atom in the ring. The monovalent C2 ~ C9 square aromatic heterocyclic bivalent group of the atomic group, and the generation time of the aromatic heterocyclic ring is preferably a group other than a hydrogen atom in the A3-AtG2 system (27) The above formula (I ) When A1 is-(CH2) 2- and Al-c (= 〇) is combined, 〇1 is pyrrolidine 11 疋, morpholine, thiomorpholine, homohexahydropyridine, and high six Hydropyridine '3' 6-tetrahydropyridine and hexahydropyridine, etc. A monocyclic C2 having a group of 1 to 2 nitrogen atoms and sulfur atoms in the ring. The G 1 t aromatic hydrocarbon 〇A] -A2-G 丨 The group a ^ a ^ g1 other than G1 is selected from 3 or a bicyclic group with a nitrogen atom and a substituent a] -a2-g 丨 ~ 3 selected If the self- or bicyclic ring is not taken as 〇A ^ A ^ G1, hexahydropyridine, 1,2 is selected from the group consisting of oxygen-C9 heterocycle-227- 200526665 (223) monovalent group 'and G1 is a gas atom and -Combined as appropriate. (28) In the above formula (I), when A1 is-(CH2) 2-, and A ^ A ^ G1 is A ^ C (= 0) -G1, they are pyrrolidine, hexahydropyridine, Morpholine, thiomorpholine, homohexahydropyridine, homohexahydropyridine, 1,2,3,6-tetrahydropyridine, and hexahydropyridine, etc. have ˜2 selected from oxygen atoms in the ring A monocyclic C2 ~ c9 heterocyclic divalent group consisting of a group of nitrogen, nitrogen, and sulfur atoms, and G1 is A ^ CC ^ o)-It is better to combine with nitrogen, but it has 1 in the ring of G1 ~ 2 monocyclic C 2 ~ 0 heterocyclic divalent groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom are selected from the group consisting of oxygen atoms, The substituent of the heterocyclic group selected from the group consisting of a nitrogen atom and a sulfur atom is preferably substituted with one or more substituents as shown in the preferred examples. (29) In the above formula (I), when A1 is-(CH2) 2_, and A ^ A ^ G1 is a combination of dagger (: (= 0) -G1), g1 is pyrrolidine, hexahydropyridine, Morpholine, thiomorpholine, homohexahydropyridine, homohexahydropyridine, 1,2,3'6-tetrahydropyridine and hexahydropyridine have 1 to 2 rings selected from oxygen atoms in the ring, A monocyclic C2 ~ C9 heterocyclic monovalent group of a group of nitrogen and sulfur atoms, and G1 is A1-C (= 〇)-It is preferable to combine with a nitrogen atom, but the ring of G1 has When 1 to 2 monocyclic C2 to C9 heterocyclic divalent groups selected from the group consisting of oxygen, nitrogen, and sulfur atoms are not substituted, the entire -A3-A4-G2 system is hydrogen (30) In the above formula (I), A] is-(CH2) 3-, and A] -A2-G1 is bonded as A ^ C (= 0) -NH-G1, When G1 is a phenyl group, the phenyl group of G 1 is substituted with one or more C 6 to C j 4 -228- 200526665 selected from the above G 1 (224) A preferred example of a substituent of an aromatic hydrocarbon group The substituent in the presenter is preferably substituted with (31) in the above formula (1), A1 is-(CH2) 3-, and A ^ A ^ G1 is A1-. (= 0) -NH-G! When the form is bound, and Gi is phenylene, and the phenylene of G1 is unsubstituted, the whole of A3-A4-G2 is a group other than a hydrogen atom. (32) A1 in the above formula (1) Is-(CH2) 3-, and A ^ AlG1 is combined in the form of A, C (= 0) -NH-G1, and gi is 1 ~ 3 in the ring, preferably 2 is selected from oxygen The monovalent or bicyclic C3 ~ C9 aromatic heterocyclic bicyclic group of an atomic group formed by an atom, a nitrogen atom, and a sulfur atom is preferred. (33) A1 in the above formula (I) is-(CH2) 3 ... and a ^ A'G1 is bonded in the form of A] -C (= 0) -NH-G1, it is in the ring] ~ 3 ', preferably 1 ~ 2 selected from oxygen atom, nitrogen The early cyclic or monocyclic ~ C9 aromatic heterocyclic divalent group of the atomic group formed by the atom and the sulfur atom, but the divalent group of the aromatic heterocyclic ring of G1 is in a ring substituted by more than one of the above In the preferred examples of the fluorenyl group having 1 to 4 heterocyclic groups selected from the group consisting of oxygen atom, nitrogen atom, and sulfur atom, the substituent is more preferably substituted. (J4) A in the above formula (1) ] Is-(CH2) 3_, and α ^ Α2 ^ 1 is bound as A ^ CM ^ O) -NH-G1, and it is a ring with ! ~ 3, preferably a monovalent or bicyclic C2 ~ 〇9 aromatic heterocyclic ring having 丨 to 2 atomic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom is However, if the divalent group of the aromatic heterocyclic ring of G1 is not substituted, it is preferred that the whole of the 3-6-4-02 system is a group other than a hydrogen atom. -229- 200526665 (225) (35) When A1 is-(CH2) 2 in the above formula (I), and ala and gI are combined in the form of ALC (= 0) .NH-y, and Gl is a single bond, A, a, and g2 are preferably a cycloalkylalkyl group formed by Cl ~ C6 acyclic aliphatic hydrocarbon group and ~ ^ alicyclic nicotyl group.

(36) In the above formula (I), when A1 is-(CH2) 3 ... and a ^ alg1 is combined as aLc (= 0) -nh-g1, and gi is a single bond, a3_a4_g2 is C as a whole] ~ C0 Acyclic aliphatic hydrocarbon group and C3 ~ (^ Cycloalkylalkyl formed by alicyclic nicotyl group is suitable, but the ring base of A3-A4-G2 is based on more than one Cl ~ C0 The non-cyclic aliphatic hydrocarbon group portion is substituted by the substituent selected in the above-mentioned preferred substituents shown in A3, or C 3 ~ C 6 alicyclic hydrocarbon group portion is substituted by C 3 ~ c 1G The alicyclic nicotyl substituent is preferably substituted by one or more of the substituents shown in the preferred examples (including those substituted by both).

(37) In the above formula (I), when A1 is-(CH2) 3-, and A〗 -A2-Gi is combined as A, C (= 0) -NH-G1, and G] is a single bond, The a3-a4-g2 system is preferably an aralkyl group formed by a Cl ~ C6 acyclic aliphatic hydrocarbon group and a C6 ~ Cig aromatic hydrocarbon group. (38) When A1 in the above formula (I) is. (CH]) 3-, and A ^ A ^ G1 is bound as A] -C (= 0) -NH-G1, and G1 is a single bond, The A3 · a4-g2 series is preferably an aralkyl group formed by an acyclic aliphatic hydrocarbon group and a C6 ~ C1 () aromatic hydrocarbon group, but the arylalkyl group of the A3-A4-G2 is best to be C] ~ [ 6 The acyclic aliphatic hydrocarbon group portion is the above-mentioned A3 substituted C! ~ C10 acyclic aliphatic hydrocarbon group, and one or more selected from the preferred examples of substituents, or the C6 ~ C1G aromatic hydrocarbon group portion is The substituted C6 ~ Cl4 -230- 200526665 (226) of the above-mentioned G2 is preferably substituted with one or more selected from the examples of preferred substituents for aromatic hydrocarbon groups (including substitution of both). (39) In the above formula (I), A] is-(CH2) 2-, and A ^ A'G1 is combined as A, C (= 0) -NH-G1, and when G1 is a single bond, A3- The A4-G2 system as a whole is a heterocyclic substituted alkyl group formed by a Cl ~ C6 # cyclic aliphatic hydrocarbon group and a heterocyclic group having 1 to 4 atoms selected from an oxygen atom, a nitrogen atom, and a sulfur atom in the ring. (40) In the formula (I), A1 is · (CH2) 3-, and A ^ AlG1 is bound as A ^ C (= 〇) -NH-G1, and when G1 is a single bond, A3-A4-G2 The whole system is an acyclic aliphatic hydrocarbon group, and a heterocyclic group formed by a heterocyclic group having 1 to 4 selected from the group consisting of oxygen, nitrogen, and sulfur atoms in the ring is substituted for the heterocyclic group, but the A3- A4-G2 heterocyclic substituted alkyl is a C! ~ C6 acyclic aliphatic hydrocarbon group part which is substituted by the above-mentioned A3 &lt; ^ ~ 0: 10. It is substituted by one or more substituents selected in the presenter, or the heterocyclic group is a heterocyclic group having 1 to 4 atoms selected from an oxygen atom, a nitrogen atom, and a sulfur atom in a substituted ring containing G2. One or more of the substituents shown in the preferred examples of the substituents are substituted by the best (including the case where both are substituted). (41) When A1, A2, G1, A3, and A4 are all shown as single bonds in the above formula (I), G2 is preferably a hydrogen atom or a Cl ~ C6 acyclic aliphatic hydrocarbon group, and (1) As mentioned in (41), the preferred combination of X'A1, A2, G2, A3, A4, and G3 of the above formula (I) can be further shown with R2-A5-a better base, that is, A5 is a single bond, In addition, R2 is a monocyclic C3 ~ C5 square aromatic heterocyclic group having 1 to 2 -231-200526665 (227) selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a substitutable ring. Among them, the R2_A5_ group or R2 is an R2-A5 group of an aliphatic nicotyl group which can be substituted, and the combination of R3 &amp; A5 is a preferred example. The preferred groups shown by A 6-are preferably combined. The pyrrolopyrimidinone derivative represented by the above formula (I) may have the following formula (III)

[Formula A], A2, A3, A4, A5, A6, G1, G2, R2 and the components gij are defined as shown in formula (I)] Tautomers as shown in the formula, these tautomers are also included in this invention. When the atom constituting the molecule of the pyrrolopyrimidone derivative represented by the above formula (I) has an asymmetric structure, its optically active substance and mixtures thereof at any content ratio are also included in the scope of the present invention. When a pyrrolopyrimidone derivative represented by the above formula (I) has a stereoisomeric structure of a molecule, the stereoisomers and mixtures thereof at any ratio are included in the present invention. The pyrrolopyrimidinone derivative represented by the above formula (I) may also have a basic group in its molecule. In this case, it can be converted into a medically acceptable acid addition salt as required. The acid may be, for example, an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, or carbonic acid; or acetic acid, citric acid, hydroxysuccinic acid, oxalic acid, tartaric acid, lactic acid, maleic acid, fumaric acid, Organic-232-200526665 (228) acids such as methanesulfonic acid. The pyridoxinone derivative of formula (I) above may have an acidic group in its molecule. At this time, it can be converted into a medically acceptable salt if necessary. The salt can be a non-toxic cationic salt. Specifically, it can be compared with alkali metal ions such as Na +, k +, alkaline earth metal ions such as Mg2 +, Ca2 +, metal ions such as a13 +, Zn2 +, or atmospheric, triethylamine, ethylenediamine, and propylenediamine 'D ratio. Organic bases such as pyridine, hexahydropyridine, hexahydropyridine, pyridine, lysine, bile test, ethanolamine, N, N-dimethylethanolamine, 4-hydroxyhexahydropyridine, glucosamine, N-methyl grapeamine The resulting salt. The definitions of A1, A2, A3, A4, A5, A6, G1, G2, R2 and R3 in the above formula (II) are respectively the same as A1, A2, A3, A4, A5, A6 'in the above formula (I), 02:: ^ and R3 have the same definition. It may be the same example as each example. In addition, the reaction of the pyrrolopyrimidinone derivative of the present invention represented by the formula (I) is led to the pyrrolopyrimidinone derivative of the formula (11), or the pyrrolopyrimidinone of the formula (11) is introduced. The derivative is guided to the pyrrolopyrimidone derivative of the present invention represented by the above formula (I), and can be removed as a barrier to chemical reactions, and can be A1, A2, A3, A4, A5, A6, &amp; The preferred examples of G2, G2, R2, and these, and the preferred combinations thereof may also be the same as those described in the pyrrolopyrimidone of the present invention represented by the formula (I). In the formula (II), X represents a chlorine atom, a bromine atom, an iodine atom, a C2 to 08 fluorenylthio group, a C2 to C8 alkoxymethylthio group, an alkyl group, or an arylsulfonyloxy group. X 1 is as follows Shown when showing chlorine atom, bromine atom, iodine atom or C! ~ 08 alkyl group or arylsulfonyloxy group. X1 is an alkyl group or an aryl-233-200526665 (229) sulfonyloxy group may be, for example, methanesulfonyloxy group, methanesulfonyloxy group trifluoride, ethanesulfonyloxy group, propanesulfone Fermentoxy, butanesulfonyloxy, tert-butanesulfonyloxy, sulfonylfluorenyl 9-fluoride, benzenesulfonyloxy, p-bromobenzenesulfonyloxy, tosylsulfonyloxy, benzylsulfonium Oxy, α-phenylethylsulfonyloxy, and Θ-phenylethylsulfonyloxy can be substituted by a substituted alkyl or aryl group and sulfonylsulfonyloxy. The preferred example of X1 is chlorine Atom, bromine atom, iodine atom, and methylsulfonyl trifluoride, especially chlorine atom and methylsulfonyl trifluoride are preferred. The compound represented by the above formula (Ic) can be prepared according to Technical knowledge 'It is very easy to produce the pyrrolopyrimidone derivative represented by the above formula (I) of the present invention. In the above (Ic), A], A2, A3, A4, A5, A6, G], G2, r2, and R3 The definitions are the same as the definitions of Aι, A2 'A3, A4, A5, A6, G1, G2, R2, and R3 in the above formula (; [), respectively, and may be the same examples as the examples. (Ic), actinide (: 2 ~ : 1 () fluorenyl group, C2 ~ C1 () alkoxymethyl group, or substituted or unsubstituted benzyl group. When q is C2 ~ CIGfluorenyl group, the C2 ~ C] group can be as follows Ethyl fluorenyl, ethyl fluorenyl trifluoride, propyl fluorenyl, butyl ethyl, isobutyl butyl, pentyl phenyl, isopentyl, trimethyl ethyl phenyl, hexamethyl phenyl, benzyl phenyl, phenyl ethyl phenyl Phenylpropenyl, and phenylpropenyl. When Q is C2 ~ cIQ alkoxymethyl, examples of the c2 ~ Cl () alkoxymethyl are methylmethyl, methoxyethoxy Methyl, tert-butoxymethyl, 2- (trimethylsulphonyl) ethoxymethyl, benzyloxymethyl, p-methoxybenzylmethyl, p-nitrobenzene Methoxymethyl, o-nitrobenzylmethoxymethyl, -234- 200526665 (230) substituted benzyl, p-methoxybenzyl, p-nitrobenzyl (trimethylsilyl and ^ Methoxyphenoxymethyl. Q is a substituted or unsubstituted benzyl system such as benzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl And p-cyanobenzyl. Preferable examples of this Q))) Ethoxymethyl. The above formula (I) Slightly chewing __ creatures can be synthesized from 批 [3, 2 • 嗔 衍生物 嗔 derivatives as shown in the above formula (η) according to the following synthesis (A).

The pyrrolopyrimidone derivative of the present invention represented by the above formula (I) is represented by formula (la) in the following synthesis method, and may be represented by pyrrolo [3, 2-d I-pyridine derivative. . [Synthesis method A]

[In the formula, Ria represents the base that can withstand the transformation reaction among those defined by the π base aLa ^ gLaIa ^ g2 in the above formula (I), and R2 A is defined by the bases represented by R and A5 in the above formula (I) Among them, can be resistant to the basis of transformation. In the definition of the base represented by R and A6 in the above formula (1), R3 A is a group that can withstand the conversion reaction. X is a non-chlorine atom, a bromine atom, an _ atom, or a Ci ~ Cs group or an arylsulfo group ]. That is, by hydrolyzing Dlt-pyrrolo [3,2.d] pyrimidine derivative (11-A), the pyrrolopyrimidone derivative (I a-A) of the present invention can be synthesized. This hydrolysis reaction -235- 200526665 (231) Use a base such as sodium hydroxide, lithium hydroxide, etc., and use a solvent such as dioxane, ethanol, 2-propanol, dimethylasco, etc., at 0 ° C ~ 150 ° C temperature range reaction. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Π), the pyrrolo [3,2-d] pyrimidine derivatives represented by the following formula (II-B) can be synthesized according to the following method ( B) is obtained from a pyrrolo [3,2-d] pyrimidine derivative represented by the above formula (Ia). [Synthesis (B)]

[In the formula, Rib represents the base that can withstand the transformation reaction among those defined by aI-^-gLaIa ^ g2 in the above formula (I). &Amp; 28 is the base of R2-A5 in the above formula (I) Among those who define the base, they can bear the base of transformation. r3b is a base that can withstand the transformation reaction in the definition of the bases represented by R and A 6 in the above formula (I). XIG is as defined above]. That is, for example, when X1G is a chlorine atom, the pyrrolopyrimidone derivative (Ia-B) of the present invention is reacted with phosphonium chloride to synthesize the pyrrolopyrimidone derivative (II-B) of the present invention. The chlorination reaction by phosphorous chloride is based on the general chlorination reaction conditions, such as in the presence or absence of triethylamine, 4-dimethylamine pyridine, and ~ methylaniline in a solvent such as acetonitrile. In the presence or absence, the reaction can be performed in the temperature range of 0 t to 150 ° C. For another example, when X 1G is methanesulfonyl trifluoride, the pyridopyrimidone derivative (la-B) of the present invention is reacted with methanesulfonic anhydride trifluoride, that is, -236- 200526665 (232) Synthesis of the pyrrolopyrimidone derivative (II-B) of the present invention. The oxidation reaction of methanesulfonium trifluoride with methanesulfonic anhydride can be carried out with pyridine, triethylamine and other amines, for example, in the presence or absence of a solvent such as dichloromethane, in the temperature range of 0t to 100t. reaction. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolo [3,2-d] pyrimidine derivatives represented by the following formula [Ia-Bl] can be synthesized according to the following method (B1) was synthesized from a 7 · cyanopyrrolo [3,2-d] pyrimidine derivative represented by the following formula (Ia-CN). [Synthesis (B 1)]

[Where RIB1 is the base that can withstand the transformation reaction among those defined by the base shown in the above formula (I), R2B] is the base defined by R2-A5 in the above formula (i), Resistant to transformation. Dimensions are the bases that can withstand the conversion reaction in the definition of the bases represented by R and A6 in the above formula (I)]. That is, the pyrrolo [3,2-d] pyrimidine derivative (Ia-CN) can be hydrolyzed to synthesize the pyrrolopyrimidone derivative (Ia-B1) of the present invention. This hydrolysis &amp; application of bases such as sodium hydroxide, lithium hydroxide, etc., in the presence or absence of hydrogen peroxide, using a solvent such as ethanol, 2-propanol, dimethyl asus, etc., at 0 ° C ~ 100. ° C temperature range reaction. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), -237- 200526665 (233) The pyrrolo [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B2) It can be synthesized from a pyrrolo [3,2-d] pyrimidine derivative represented by the above formula (ia_Bl) according to the following synthesis method (B2). [Synthesis method (B 2)]

(Ia-Bl)

(M2) [wherein R1B2 is a base that can withstand the transformation reaction among those defined by Ai-A ^ GLA ^ AtG2 in the above formula (I), and R2B2 is R2-A5 in the above formula (I) Among the base definitions shown, the bases can be resistant to transformation]. That is, Huffman transposes the pyrrolopyrimidine derivative (Ia-Bl) 'of the present invention to synthesize the pyrrolopyrimidinone derivative (Ia-B2) of the present invention. This Huffman translocation reaction uses, for example, sodium hypochlorite, bromine, benzyltribromide tribromide, and other reagents, in the presence or absence of a base such as sodium hydroxide, using ethanol, 2-propanol, acetonitrile, Solvents such as water. &lt;: ~ 1 5 (TC temperature range reaction.) Among the pyrrolop [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolop [3,2 shown by the following formula (Ia-B3) -d] Pyrimidine derivatives can be synthesized from pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B2) according to the following synthesis method (B3). -238- 200526665 (234) [Synthesis Law (B3)

(Ia-B2)

(Ia-B3) [wherein R1B3 represents the base that can withstand the conversion reaction among those defined by aLa'G ^ aIaLg2 in the above formula (I), and r2B3 is R2-A5 in the above formula (I) Among the base definitions shown, those that can tolerate transformation. R3B3 system The above-mentioned system shows a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom]. That is, 'the pyrrolopyrimidinone derivative (Ia-B2) of the present invention is allowed to react with nitrous acid or nitrite, and a Sandrneyer type reaction is performed', so that the pyrrolopyrimidone derivative of the present invention can be synthesized. (I a _ B 3) ° For the reaction of Sandmia type using nitrous acid or nitrite, reagents such as nitrous acid, sodium nitrite, isoamyl nitrite, and tert-butyl nitrite are used. 'When fluorine atoms are introduced, they are hydrogen fluoride or hydrofluoric acid; when chlorine atoms are introduced, they are, for example, copper chloride or carbon tetrachloride; when bromine atoms are introduced, they are, for example, tetramolybdenum carbon or bromoform; In the presence of a halogenating agent such as iodine, in the presence or absence of an acid such as sulfuric acid and hydrochloric acid, a solvent such as ethanol, acetonitrile, and water is used to react at a temperature range of 〇c to 〇50. Among the pyrrolop [3,2 · d] pyrimidine derivatives represented by the above formula (I a-B), the pyrrolop [3,2 _ d] pyrimidine derivatives represented by the following formula (I a · B 4) can be determined by The following oral preparation method (B4) is synthesized from the D (t-pyrrolo [3,2-d] pyrimidine derivative represented by the above formula (Ia-B2). -239- 200526665 (235) [Synthesis method (B4)]

* R2

(M2) (Ia-B4) [wherein r1B4 represents the base that can withstand the conversion reaction among those defined by aLaIgLaIa ^ G2 in the above formula (I), and r2B4 is R2- in the above formula (I) Among the base definitions shown in A 5, the bases that are resistant to transformation]. That is, the pyrrolopyrimidinone derivative (Ia-B2) of the present invention is allowed to react with nitrite or nitrite to synthesize the pyrrolopyrimidinone derivative (Ia-B4) of the present invention. In the reaction using nitrous acid or nitrite, reagents such as nitrous acid, sodium nitrite, isoamyl nitrite, and tert-butyl nitrite are used. In the presence of acids such as sulfuric acid and hydrochloric acid, dimethyl formamide is used. Solvents such as hydrazine, tetrahydrofuran, ethanol, and water are reacted at a temperature ranging from 0 ° C to 150 ° C. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolop [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B5) can be determined according to The following synthesis method (B5) is synthesized from a pyrrolo [3,2-d] pyrimidine derivative represented by the above formula (Ia-B4). -240- 200526665 (236) [Synthesis (B5)]

(Ia-B5) [wherein R1B5 represents the base that can withstand the transformation reaction among those defined by aLaIgLaLa ^ G2 in the above formula (I), and r2B5 is represented by R2-A 5 in the above formula (I) Among those who define the base, they can bear the base of transformation]. That is, the pyrrolopyrimidone derivative (Ia-B4) of the present invention can be synthesized with the pyrrolopyrimidone derivative (Ia-B5) by reacting nitric acid or nitrogen dioxide. For the reaction using nitric acid or nitrogen dioxide, reagents such as nitric acid, nitrogen dioxide, ammonium nitrate, and sodium nitrite can be used in the presence or absence of sulfuric acid, hydrochloric acid, acetic acid, and ozone. Solvents such as methyl chloride, acetonitrile, water, etc., are reacted at a temperature range. Among the pyrrolo [3,2 · d] pyrimidine derivatives represented by the above formula (I a-B), the pyrrolo [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B6) may be as follows Synthesis method (B6) 'Synthesized from the pyrrolo [3,2-d] -pyridine derivative represented by the above formula (Ia-B6a). -241-200526665 (237) [Synthesis (B 6)]

[Wherein R] B6 represents a base that can withstand the transformation reaction among those defined by the bases in formula (1) above, and is resistant to the bases defined by R2-A5 in formula (1) above Based on the transformation. Rule ^^ is not a bromine atom or an iodine atom. The above r3b6 formula (z) in the definition of R3 shows a substituted or unsubstituted saturated aliphatic hydrocarbon group, a substituted or unsubstituted C3 ~ C8 alicyclic hydrocarbon group, a substituted or unsubstituted C6 ~ C "aromatic hydrocarbon group, substituted Or the unsubstituted ring contains 1 to 2 monocyclic C3 to C5 aromatic heterocyclic groups, or trimethylsilyl groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom].

That is, in the presence of a catalytic amount of palladium, the pyrrolopyrimidinone (Ia-B6a) of the present invention is allowed to interact with the terminal alkyne derivative represented by the formula R3B6-CeC-H to synthesize the pyrrolopyrimidine of the present invention Ketone derivatives (1a_B6). That is, 'the reaction system using terminal alkyne derivatives with a catalytic amount of palladium and terminal alkyne derivatives ~' uses palladium catalysts such as tetrakis (triphenylphosphine) palladium, bis (triphenylphosphine) palladium, and palladium acetate, In the presence or absence of ligands such as triphenylphosphine, tri (o-tolyl) phosphine, 1, i'-bis (diphenylphosphine) ferrocene, etc., in diethylamine, diethylamine, hexahydropyridine In the presence of a base such as pyrrolidine and pyrrolidine, the reaction is performed using a solvent such as tetrachloromethane, dimethylformamide, and toluene at a temperature ranging from 0 t to i 5 0 t • 242- 200526665 (238). Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolo [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B7) can be synthesized according to the following method ( B6), synthesized from a pyrrolo [3,2-d] pyrimidine derivative represented by the above formula (Ia-B7a). [Synthesis (B7)]

(Ia-B7a)

(Ia-B7) [where R represents the base defined by Ai-AlGi-AS-ALG2 in formula (I) above, which can withstand the transformation reaction, and r2b? Is in formula (i) above Among those defined by the bases shown by R2-A5, bases that are resistant to transformation. R3B7a represents a bromine atom or an iodine atom. B3B7 is a substituted or unsubstituted C6 to CM aromatic hydrocarbon group or a substituted or unsubstituted ring having 1 to 4 members selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the R3 group defined by the formula (I). Clusters of aromatic heterocyclic groups]. That is, in the presence of a catalyst amount of palladium, the pyrrolopyridinone derivative (Ia-B7a) and the boric acid derivative [R3B7-B (OR) 2 of the present invention are used; here, R3B7 is the same as the above-mentioned synthesis method (B7 ) Has the same definition, and R is a hydrogen atom or an alkyl group], and the pyrrolopyrimidone derivative (Ia-B7) of the present invention can be synthesized. That is, in the reaction using a catalyst amount of palladium and a boric acid derivative, bis (triphenylphosphine) palladium, palladium acetate, and tris (diphenylmethyleneacetone) dipalladium-chloroform are used together with the boric acid derivative. Catalysts such as palladium, in the presence or absence of ligands such as 200526665 (239) triphenylphosphine, tri (o-tolyl) phosphine, 1,1, -bis (triphenylphosphino) ferrocene, etc. In the presence of alkalis such as potassium phosphate, sodium carbonate, potassium hydroxide, sodium ethoxide, etc., using a solvent such as tetrahydrofuran, dimethylformamide, 2.propanol, water, etc., at a temperature range of 0 ° C ~; 50 ° C reaction. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolo [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B8) can be synthesized according to the following method (B8) is synthesized from a pyrrolo [3,2-d] pyrimidine derivative represented by the formula (Ia-B8a). [Synthesis (B8)]

(Ia-B 8a) (Ia-B8) [where r1B8 represents the base that can withstand the conversion reaction among those defined by the formula (I) represented by aLa'gLaIaIg2, and R2B 8 is the above formula (I) In the definition of the base shown by R2-A5, the base is resistant to the transformation reaction. R3B8a represents a bromine atom or an iodine atom. R3B8 shows the definition of R3 in the above formula (I)]. That is, in the presence of a catalytic amount of palladium, a terminal olefin derivative is allowed to act on the pyrrolopyrimidone derivative (Ia-B8a) of the present invention, so that the pyrrolopyrimidone derivative (Ia-B8) of the present invention can be synthesized. That is, in the reaction using a catalytic amount of palladium with a terminal olefin derivative, it is used together with a terminal olefin derivative such as palladium chloride, palladium acetate, tris (diphenylmethyleneacetone) dipalladium-chloroform addition -244 200526665 (240) palladium catalysts in the presence or absence of triphenylphosphine, tri (o-tolyl) phosphine, 1, 丨, · bis (— ^^) monopentyl temple ligand In the presence of a base such as sulphuric acid, potassium carbonate, potassium hydroxide, triethylamine, etc., using a solvent such as tetrahydrofuran, monomethylmethanamine, water, etc., at a temperature range of 0 ° C to 150 ° C Perform the reaction. In addition, the pyrrolopyrimidone derivative (Ia_B8) of the present invention can also be contacted with semi-reduction or borohydride-protonation to synthesize a pyrrolo [3,2-d] pyrimidine derivative having an alkynyl group obtained according to the synthesis method (B6). (La_B6). That is, the contact half-protozoic reaction is performed in the presence of a palladium catalyst such as fine barium sulfate-quinoline, inactive carbon-D quinoline, and the like in a hydrogen atmosphere using a solvent such as methanol, ethanol, and tetrahydrofuran. t ~ 100 ° C temperature range is sufficient. In the borohydride-protonation reaction system, borohydride can be performed using a borohydride reagent such as 9-borabicyclo [3 · 3 · 1] nonane or dicyclohexylmethylboron, and then protonated with acetic acid. In this reaction, solvents such as tetrahydrofuran, diethyl ether, dichloromethane, and toluene can be used at 0 ° C to 100 ° C. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolop [3,2-d] pyrimidine derivatives represented by the following formula (Ia · B9) may be as follows The synthesis method (B9) is synthesized from a pyrrolo [3,2-d] pyrimidine derivative represented by the formula (Ia-B9a). [Synthesis (B 9)]

(Ia-B9a) (Ia-B9) 245- 200526665 (241) [where r1B9 represents the base defined by a ^ a ^ gLa ^ aLg2 in formula (i) above, which is resistant to the transformation reaction. R2b9 is a radical that can withstand the conversion reaction in the definition of the radical represented by R2-A5 in the above formula (I). R3B9a represents a bromine atom or an iodine atom, and R3B9 represents a substituted or unsubstituted saturated aliphatic hydrocarbon group, a substituted or unsubstituted C] ~ C! G alicyclic hydrocarbon group or vinyl group]. That is, in the presence of a catalytic amount of palladium or nickel, the pyrrolopyrimidinone derivative (la-B 9a) of the present invention can be reacted with an organometallic reagent to synthesize the pyrrolopyrimidinone derivative (Ia- B9). That is, the reaction using a catalyst amount of palladium or nickel and an organometallic reagent is used as an organic zinc reagent such as phenyl zinc chloride, and an organic zinc reagent prepared from Glia reagent and zinc chloride is used as Organotin reagents such as phenyltrimethyltin and tetramethyltin, as Grignard reagents may be organometallic reagents such as phenylmagnesium bromide, n-butylmagnesium bromide, etc. (Triphenylphosphine) palladium, tris (diphenylmethyleneacetone) dipalladium-chloroform adduct, {1,1, _bis (diphenylscalyl) ferrocene} palladium, or nickel contact Examples of the medium are {i, 3- bis (diphenylphosphino) propane} nickel, nickel bromide, triphenylphosphine, tri (o-tolyl) scale, 1 ′,-bis (diphenylphosphino) In the presence or absence of a ligand such as ferrocene, a solvent such as diethyl ether, tetrahydrofuran, dimethylformamide and the like is used at 0 ° C to 150 ° C. (: Temperature range reaction. In addition, the pyrrolopyrimidone derivative (Ia-B9) of the present invention can also be obtained by hydrogen back-to-original formation method (B6), and the pyrrolo [3,2-d] pyrimidine derivative having an alkenyl group ( U-B6), or the pyrrolo [3'2_d] umidine derivative (Ia_B8) with alkenyl group obtained by the synthesis method (B8). This hydrogen reduction trans-246 · 200526665 (242) should be In the presence of a medium of palladium activated carbon, in a hydrogen atmosphere, using a solvent such as methanol, ethanol, tetrahydrofuran, etc., to react at 100 ° C; pyrrolo [3,2-d] pyrimidine represented by the above formula (Ia-B) Among the derivatives, the pyrrolo [3,2-d] pyrimidine derivative represented by the following formula (Ia-BIO) can be obtained from the pyrrolo [3,2-d shown by the formula (Ia-B10a) according to the following synthesis method (B10): ] Pyrimidine derivatives. Biosynthesis. [Synthesis (B10)]

[In the formula, R1B10 is the base that can withstand the conversion reaction among those defined by the formula A ^ A ^ GLaIa4-G2 in the formula (I), and R2BI () is the formula R1 to A5 in formula (I). In the definition of the base, the base can withstand the transformation reaction. 11381 () 3 shows a bromine atom or iodine atom, and R3B1G shows c2 ~ c1 () hydroxy, alkoxy, N-substituted amino or N, N-disubstituted amino]. That is, the pyrrolopyrimidinone derivative (Ia-B 10a) of the present invention is reacted with carbon oxide in the presence of a catalytic amount of palladium to synthesize the pyrrolopyrimidinone derivative (Ia-BIO) of the present invention. That is, the carbonyl insertion reaction using a catalyst amount of palladium is performed in a carbon monoxide atmosphere, and as the palladium catalyst, for example, tetrakis (triphenylphosphine) palladium, palladium acetate, and tris (diphenylmethyleneacetone) dipalladium- Chloroform adducts, in the presence or absence of ligands such as triphenylphosphine, tri (o-tolyl) phosphine, 1,1'-bis (diphenylphosphino) ferrocene, in potassium carbonate, triethyl In the presence or absence of a base such as amine, a solvent such as acetonitrile, tetrahydrofuran-247-200526665 (243) an, dimethylformamide, etc. is used at 0 ° C to 150 ° C. (: Reaction. At this time, it can be synthesized as a carboxyl group when water is added as a reactant, and introduced into a oxo group when alcohol is added. An N-substituted or n, N-disubstituted amine carbonyl group is added to the primary or secondary amine. Compounds.

Among the pyrrolop [3,2 · d] pyrimidine derivatives represented by the above formula (I a-B), the following formula is shown. (I a-B 1 1) pyrrolo [3,2-d] pyrimidine derivatives According to the following synthesis method (B11), it can be synthesized from the d ratio shown in formula (Ia-Blla) and the [3,2-d] glutamidine derivative. [Synthesis method (B 1 1)]

[In the formula, r1B11 is a base that can withstand a conversion reaction among those defined by aLaIgLaIa ^ g2 in the above formula (I), and r2BI1 is a base that can be defined by the base represented by R2-A5 in the above formula (I). Resistant to the base of change reactions. R3Blla represents a bromine atom or an iodine atom. That is, in a carbon oxide atmosphere, the pyrrolopyrimidinone derivative (la-B1 la) of the present invention is reacted with a reducing agent in the presence of a catalyst amount of palladium to obtain the pyrrolopyrimidinone derivative of the present invention. (I a-B 1 1). That is, in the formazanation reaction using palladium in a catalyst amount, under a carbon monoxide atmosphere, tetrakis (triphenylphosphine) palladium, palladium acetate, and tris (diphenylmethyleneacetone) diamine are used as palladium catalysts. Palladium-chloroform adduct in the presence or absence of ligands such as triphenylphosphine, tri (o-tolyl) phosphine, 1,1'-bis (diphenylphosphino) ferrocene, etc. -248- 200526665 (244 ) In the presence or absence of a base such as potassium carbonate, triethylamine, and the like, a solvent such as acetonitrile, tetrahydrofuran, and dimethylformamide is used to react at 50 ° C to 50 ° C. At this time, if a reducing agent such as tributyltin hydride or triethylsilane is added, a methylamyl group may be introduced, and an organometallic reagent such as an alkyl zinc reagent, an alkylboron reagent, or an organotin reagent may be added to introduce an alkylcarbonyl group. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (ia-B), the pyrrolop [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B12) may be as follows Synthesis method (B12) is synthesized from a pyrrolo [3,2-d] pyrimidine derivative represented by formula (ia-B12a). [Synthesis method (B 1 2)]

[In the formula, R1B12 represents the base that is resistant to transformation reaction among those defined by aLa2-GI_a3-A4_g2 in formula (I) above, and R2B12 represents the definition of the base represented by r2_a5 in formula (I) above Resistant to the base of change reactions. R3B12a represents a bromine atom or an iodine atom]. That is, 'the pyrrolopyrimidone derivative (; [a-B 1 2 a) of the present invention is reacted with a reagent available for methyl trifluoride to synthesize the pyrrolopyridone derivative of the present invention (ia -B 丨 2). That is to say, the trifluoromethylation reaction system can use trifluoromethyl donors such as sodium trifluoride or methyl trifluoroacetate, and simultaneously use cuprous iodide or fluorinated planer. Of methyl zinc compound or methyl cadmium trifluoride compound and cuprous bromide to prepare methyl copper trifluoride-249- 200526665 (245) compound, or from methyl iodide trifluoride and copper powder The method of methyl copper trifluoride compound uses dimethylformamide, N-methylpyrrolidone, hexamethylphosphamide, acetonitrile, pyridine and other solvents at a temperature of 0 to 150 ° C.

Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolo [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B 1 3) may be as follows Synthesis method (B13) is synthesized from a pyrrolo [3,2-d] pyrimidine derivative represented by formula (Ia-B13a). [Synthesis method (B 1 3)]

[Wherein r] b] 3 is a base which is resistant to transformation reaction among those defined by aLaLgLaIa ^ g2 in formula (I) above, and R2B13 is a base represented by R2-A5 in formula (I) The definition can be resistant to the basis of the transformation reaction. ] The pyrrolopyrimidinone derivative (Ia-Bl 3a) of the present invention is reacted with water in the presence of nitrous acid to synthesize the pyrrolopyrimidinone derivative (Ia-B13) of the present invention. That is, in the hydroxyl reaction in the presence of nitrous acid, sodium nitrite or isoamyl nitrite is used, in the presence of an acid such as trifluoroacetic acid or sulfuric acid, in the presence of a co-solvent such as acetonitrile, dimethylformamide, or In the absence of water, the reaction is carried out at 0 ° C to 150 ° C with water as the solvent. Among the pyrrolop [3,2-d] pyrimidine derivatives represented by the above formula (Ia-B), the pyrrolop [3,2-d] pyrimidine derivatives represented by the following formula (Ia-B14) can be prepared according to -250- 200526665 (246) The following synthesis method (B14) was synthesized from a pyrrolo [3 '2-d] pyrimidine derivative represented by the formula (Ia-B14a). [Synthesis method (B14)]

[In the formula, R1B14 is a group that can withstand the conversion reaction among those defined by ALA ^ GkA ^ A ^ G2 in formula (I) above. 'R2B 14 is shown by R2-A5 in formula (I) above. In the definition of the radical, the radical which can withstand the shift reaction is shown. R3B14 shows C] ~ C6 aliphatic hydrocarbon group]. That is, the pyrrolopyrimidone derivative (Ia-B 14a) of the present invention is reacted with water in the presence of nitrous acid to synthesize the pyrrolopyrimidone derivative (Ia-BM) of the present invention. That is, the alkyl sulfur reaction in the presence of nitrous acid uses sodium nitrite or isoamyl nitrite, and in the presence or absence of acids such as hydrochloric acid or sulfuric acid, dialkyl disulfide or alkanethiol is used as the Reagent, using acetonitrile, dimethylformamide, etc. as a solvent, the reaction was carried out up to 150 t. Pyrrole shown in (Ia-B) of the above synthesis method (B) or (CN) of the synthesis method (β1) [ Among the 3,2-d] pyrimidine derivatives, pyrrolidine [3,2-d] pyrimidine derivatives represented by the following formula (ia_c2) may be a

The aW F synthesis method (C) is synthesized from the following formula (Ia-Cl). -251-200526665 (247) [Synthesis method C]

[In the formula, RIC is a group that is resistant to the conversion reaction among those defined by Ai-A2-GLAlA4-G2 in the above formula (I), r2ci is a chlorine atom or bromine atom, and r3C is a non-cyano group or the above. In the formula (I), a group defined by a6_r3 is a group that can endure a shift reaction. When A5 is -NR2 () 1 (the definition of R2G1 is the same as that of R2 01 in the above formula (I)), R2c2 is shown by removing fluorine atom, chlorine atom, bromine from the definition of R2 in the above formula (I) For atoms and stele atoms, when A5 is a bond showing a single bond, r2c "sr2c2 and the bonded a5 represent a substituted or unsubstituted nitrogen atom. The ring has 1 to 4 members selected from oxygen, nitrogen, And a heterocyclic group consisting of a group of sulfur atoms]. That is, 'the primary or secondary amine is reacted with the pyrrolopyrimidone derivative (Ia-Cl) of the present invention, and the pyrrolopyrimidone derivative of the present invention can be synthesized. (Ia-C2). Through the amination reaction of primary or secondary amines under solvent-free conditions or using dimethylmethylene, dimethylformamide, dioxane, tetrahydrofuran, toluene, etc. Solvent in the presence or absence of bases such as pyridine, triethylamine, diisopropylethylamine, 4-dimethylaminopyridine, sodium carbonate, etc., in a mixture of palladium salts such as palladium acetate and phosphorus such as triphenylphosphine In the presence or absence of the transition metal complex catalyst generated by the radical, the reaction is carried out at 0 ° c to 15 ° r. The above formula (la) or the synthesis method (B 1) In the pyrrole-252- 200526665 (248) and [3,2-d] pyrimidine derivatives represented by (Ia-CN), pyrrole [3 '2-d] pyrimidine D shown in the following formula (Ia_D2) Derivatives can be synthesized according to the following synthesis method (0) from the formula (ia_D 1) and [3, 2-d]. [Synthesis method (D)]

(Ia-Dl) (Ia-D2) [wherein 1110 is a base represented by Ai-AtG ^ AlAtG2 in the above formula (I), and a base which is resistant to the transformation reaction in the test is defined. r2d! is a chlorine atom or a bromine atom. R2O2 is a substituted or unsubstituted c6 ~ Cl4 aromatic hydrocarbon group, or a substituted or unsubstituted aromatic heterocyclic ring having 1 to 2 aromatic heterocyclic rings selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. The radical is a radical which is resistant to a shift reaction in the definition of the radical represented by A6-R3 in the above formula (I)]. That is, the pyrrolopyrimidone derivative (I a- D 1) of the present invention and, for example, a boronic acid derivative [R2D2-B (OR) 2; wherein the definition of r2D2 is the same as the definition of R2D2 in the above synthesis method (D) In the same way, R is a hydrogen atom or an alkyl group], and the pyrrolopyrimidone derivative (Ia-D2) of the present invention can be synthesized. The reaction with boric acid derivatives is generally based on the conditions of the Suzuki reaction. For example, using a solvent such as 2-propanol and / or water, using a catalyst such as palladium acetate in the presence of an inorganic base such as sodium carbonate, and adding triphenylphosphine as the The ligand is reacted from 0 ° C to 150 ° C. Among the pyrrolop [3,2-d] pyrimidine derivatives represented by the above formula (la) or (Ia-CN) in the synthetic method (B1), the pyrrolop [3 • 253- 200526665 is represented by the following formula (Ia-E2): (249) The 2-d] pyrimidine derivative can be synthesized from a pyrrolo [3'2-d] pyrimidine derivative represented by the following formula (Ia_El) according to the following synthesis method (E).

[In the formula, 111 £ is a base shown by aLaIgLaIa ^ g2 in the above formula (I), and a base of which is defined to be resistant to changeover reactions. r2E represents a chlorine atom, a bromine atom, or an iodine atom. r3E represents a cyano group or a group that is resistant to a shift reaction in the definition of the group represented by R6 · A3 in the formula (I). That is, the pyrrolopyrimidone derivative (Ia-El) of the present invention can be halogenated to obtain the pyrrolopyrimidone derivative (Ia-E2) of the present invention. The halogenation reaction system uses, for example, halogenating reagents such as N-chlorosuccinimide and N-bromosuccinimide, in the presence of a solvent such as dimethylformamide, dioxane, and tetrahydrofuran. 20t ~ 150 ° C for reaction. Among the pyrrolo [3,2-d] pyrimidine derivatives represented by the formula (10 or the synthetic method (B1) (Ia-CN)), the pyrrolop [3'2] is represented by the following formula (Ia_F): -d] Pyrimidine derivatives can be synthesized from the following formula (IV-F) without using [3,2-dp memididine derivative according to the following synthesis method (F). -254- 200526665 (250) [Synthesis method (F)]

[Wherein r] f is a base represented by a'aIgLaIa ^ g2 in the above formula (I), and is a base which can withstand a conversion reaction among those defined. R2F is a carbon atom of a pyrrole ring bound to a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, and R2F in the definition of the formula (J) represented by R2, and the substituted or unsubstituted ring having a nitrogen atom has 1 ~ 4 heterocyclic groups selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, R3F is a cyano group or a group that is resistant to transformation in the definition of AL r3 in the above formula (I)]. That is, the pyrrole derivative represented by the above-mentioned formula (IV-F) can be synthesized by cyclization using formamidine or formamidine, and the pyrrolop [3 '2- d] pyrimidine derivatives. The cyclization reaction using formazan uses a formazan acetate salt and 2-propanol or the like as a solvent, and the reaction is performed at ~ 150 ° C. In addition, the cyclization reaction of formamidine is carried out by using bases such as formamidine and sodium methoxide in the presence or absence of a solvent such as dimethyl arylene or dimethoxyethane at G ° C ~ 1 5 (TC The reaction proceeds smoothly. The pyrrolo [3,2-d] pyrimidine derivative represented by the formula (la) or (Ia-CN) of the synthesis method (B 1) can be synthesized from the following formula (G) according to the following synthesis method (G) IG) is synthesized by a pyrrolo [3,2-d] pyrimidine derivative. -255- 200526665 (251) [Synthesis (G)]

• [In the formula, R1G is the base shown by A ^ / ^ Gi-AlAtG2 in the above formula (I), and is defined as a base that can withstand the conversion reaction. 1126 is a base which can withstand a shift reaction in the definition of the base represented by R2-A5 in the above formula (I). In the definition of a cyano group or a group represented by A6-R3 in the above formula (I), a group that can withstand the transformation reaction, Q is a C2 ~ C1G group which may be substituted, and a C2 ~ C.1G group which may be substituted. Alkoxymethyl, or substituted or unsubstituted benzyl]. That is, for example, when Q is a fluorenyl group, the pyrrolopyrimidinone derivative (I · G) of the present invention can be reacted with a fluorenyl halide to synthesize the pyrrolopyrimidinone derivative (Ib-G) of the present invention. . The fluorination reaction of fluorenyl halides can be performed according to general fluorination reaction conditions, for example, in the presence of triethylamine or pyridine, at 0 ° C to 10 ° C. Also, for example, Q is a In the case of oxymethyl and benzyl, the pyrrolopyrimidinone derivative (I-G) of the present invention can be reacted with an alkoxymethyl halide or benzyl halide to synthesize the pyrrolopyrimidine of the present invention. A ketone derivative (I-G). The reaction by an alkoxymethyl halide or a benzyl halide can be carried out in the presence of sodium hydride at 0t: ~ 100 ° C. According to the present invention obtained Pyrrolopyrimidone derivatives (Ib-G) can be converted to reactions known to practitioners of A], A2, A3, A4, A5, A6, (5), G2, R2, and / or 113. The pyrrole [ 3,2-d] pyrimidine derivatives • 256- 200526665 (252) (I b-G) is hydrolyzed under neutral or basic conditions when Q is fluorenyl, and trifluoro when q is alkoxymethyl The hydrolysis reaction is performed under acidic conditions such as acetic acid. When R3 is a benzyl group, a hydrogenation reaction is performed to convert it into the pyrrolopyrimidone derivative (I-G) of the present invention. The pyrrolopyrimidinone derivatives of the present invention synthesized according to the above-mentioned synthesis methods (A), (B), (C), (D), (E), (F), and (G) are those having a oxo group, Oxygen, aromatic nitro, and other easily convertible substituents can be subjected to well-known reactions of the industry, and can be converted into the D [t-pyrolo-B-one ketone derivatives of the present invention each having a carboxyl group, a hydroxyl group, and an amine group. If the pyrrolopyrimidone derivative of the present invention synthesized by the above synthesis methods (A), (B), (C), (D), (E), (F), and (G) has a carboxyl group, A well-known condensation reaction can be converted into a pyrrolopyrimidone derivative of the present invention having an alkoxycarbonyl group, a carbamoyl group, an N-alkylaminoformyl group, and the like. The above synthesis methods (A), (B), (C) ), (D), (E), (F), and (G) when the pyrrolopyrimidinone derivatives of the present invention have an amine group, it can be converted to a fluorenyl group by a condensation reaction known to the industry. Pyrrolopyrimidinone derivatives of the present invention such as sulfanylamino groups. Also, when having an amine group, it can be converted by a reductive alkylation reaction well known to the practitioner. A pyrrolopyrimidinone derivative of the present invention having a monoalkylamino group or a dialkylamino group. The above synthesis methods (A), (B), (C), (D), (E), (F), and (G) When the synthesized pyrrolopyrimidone derivative of the present invention has a hydroxyl group, it can also be converted to a pyrrolopyrimidone derivative of the present invention by a condensation reaction well known to industry practitioners, which has a fluorenyl-257-200526665 (253) group. The pyrrolopyrimidinone derivatives of the present invention synthesized by the methods (A), (B), (C), (D), (E), (F), and (G) can also be used in the case of a methylpyridyl group. A well-known reductive alkylation reaction is converted into a pyrrolopyrimidone derivative of the present invention having an alkylaminomethyl group and the like. In the method for synthesizing a pyrrolopyrimidone derivative represented by the above formula (I), the pyrrole derivative represented by the above formula (IV-F) used as a starting material can be represented by the following formula (VI-H) The 3-alkoxyacrylonitrile derivative is synthesized according to the synthesis method (ii). [Synthesis (Η)]

[The ruler in the formula is the base defined by aLaIgLaIa ^ g2 in the above formula (I), and it is a base that can withstand the conversion reaction. R2HS In the definition of the group represented by R ^ A5 in the above formula (I), the carbon atom of the pyridine ring except fluorine atom, chlorine atom, bromine atom, iodine atom, and R2Hg is removed, and the substituted or unsubstituted ring bonded to the nitrogen atom is shown. It has 1 to 4 heterocyclic groups selected from the group consisting of oxygen, nitrogen, and sulfur atoms. R3H is cyano or can be resistant to the definition of the group represented by A6-R3 in the formula (I). Based on the transformation reaction]. That is, an amine acrylonitrile derivative (VH) can be synthesized by reacting an alkoxyacrylonitrile (VI-H) with a primary amine (κΛΝΗ2; R] has the same definition as R1 in the above synthesis method (ii). . In the presence of a base, the pyrrole derivative (IV-H) can be synthesized by reacting this amine-258-200526665 (254) propionitrile nitrile derivative (V-H) with methyl bromoacetate and then cyclizing it. ^ The reaction between oxopropionitrile derivative (VI-H) and primary amine is carried out using a solvent such as methanol, ethanol, or isopropanol, and the reaction is carried out in a process of 0 to i. (Ν · Η) The reaction with methyl bromoacetate uses a base such as sodium carbonate and acetonitrile as a solvent, and it is performed in the form of a pyrrolidopyrimidone derivative represented by the above formula (I). Among the pyrrole derivatives represented by the above formula (IV-F) used as a starting material in the synthesis method, a pyrrole derivative wherein R2F is a hydrogen atom can be obtained from, for example, a 3-oxy group represented by the following formula (VII-J) Acrylonitrile derivatives were synthesized according to the synthesis method (j). [Synthesis method (J)]

[In the formula, R &quot; is a base defined by aLaIgLaIa ^ G2 in the above formula (I), and is a base that can withstand a conversion reaction. Is a radical which is resistant to a shift reaction in the definition of a radical represented by R or A3 in the above formula (I)]. That is, by reacting a 3-oxyacrylonitrile derivative (VII-j) with a primary amine (Ri_NH2; R1 is the same as defined in the above synthesis method (J)), an aminoacrylonitrile derivative ( VJ). In the presence of a base, this -259- 200526665 (255) aminoacrylonitrile derivative (V-J) is reacted with methyl bromoacetate and then cyclized to synthesize a pyrrole derivative (IV-J). The reaction of 3-oxyacrylonitrile derivative (VI-J) with primary amine is carried out using a solvent such as methanol, ethanol or isopropanol at 0 ° C ~ 1 oot to react the aminoacrylonitrile derivative (VJ) with The reaction of methyl bromoacetate uses a base such as sodium carbonate and acetonitrile as a solvent, and the reaction is performed at 0 ° C to 150 ° C.

Among the pyrrole derivatives represented by the above formula (IV-J) used as a starting material in the method for synthesizing the pyrrolopyrimidone derivative represented by the above formula (I), a pyrrole derivative wherein 1 ^ 〃 is a hydrogen atom is usable Another method is, for example, synthesis (K) synthesis. • [Synthesis method (K)]

(VII-K) (V-K)

(ιν · κ) [In the formula, the rule ^ is the base shown by aLaIgLaLa ^ G2 in the formula (I) above, and it is a base that can withstand the conversion reaction among those defined. r3K is a cyano group or a group that is resistant to a shift reaction in the definition of the group represented by R6-A5 in the above formula (I)]. In other words, the 3-oxyacrylonitrile derivative (VII-K) and the glycine methyl ester derivative (Ri-NH-CKOOCHr R1) having R1 on the nitrogen atom have the same definition as R1 in the synthesis method (K). ) Reaction to synthesize amine-260-200526665 (256) propane; If nitrile derivative (vK). Cyclization of this aminoacrylonitrile derivative (V-K) in the presence of a base can be synthesized into a pyrrole derivative (丨 v_κ). The cyclization reaction of a 3-oxyacrylonitrile derivative (ν-κ) uses, for example, a 1,8-diazo ring [5,4,0] -7-undecene or carbonic acid as a base, Using acetonitrile or ethylene glycol dimethyl ether as a solvent, the reaction is performed at 0 ° C to 150 ° C. The pyrrolopyrimidone derivative represented by the above formula (I) thus obtained has the effect of blocking GSK-3 activity, and can be used as a GSK-3 activity blocker as a clinically applicable preventive agent and / or treatment Agent. Diseases that can be treated with GSK-3 activity blockers include diabetes, diabetic flare, atherosclerotic arteriosclerosis, hypertension, hypertrophy, symptom cluster X, Alzheimer's disease, neurodegenerative diseases (AIDS encephalopathy , Dance step disease, Parkinson's disease, cerebral ischemia), bipolar disorder, traumatic brain injury, hair loss, inflammatory diseases, cancer, and immunodeficiency. The pyrrolopyrimidinone derivative represented by the above formula (I) and a medically acceptable salt system can be used as a pharmaceutical composition together with a pharmaceutically acceptable carrier and / or diluent. The pharmaceutical composition can be formed into various dosage forms and administered orally or parenterally. Parenteral administration can be, for example, intravenous, subcutaneous, intramuscular, transdermal, intrarectal. The dosage form for oral administration may be, for example, lozenges, nine doses, granules, powders, liquids, suspensions, syrups, capsules, and the like. Here, the method of forming a tablet can use an excipient, a binding agent, a disintegrating agent, etc. to prepare a pharmaceutically acceptable carrier according to a general method. Nine doses, granules, powders can also be formed in the same manner as in the case of tablets, using excipients and the like. The liquid, suspension and sugar-violet agents are formed using glycerol-vinegar-261-200526665 (257), alcohols, water, vegetable oil, etc. by the usual methods. The method for forming capsules can be filled with granules, powders, or liquids in capsules such as gelatin. In the case of parenteral administration, it can be administered as an injection when it is administered intravenously, subcutaneously, or intramuscularly. The injection can be, for example, one dissolved in a water-soluble solution such as physiological saline, or one insoluble in a propylene glycol, polyethylene glycol, or vegetable oil organic ester. For transdermal administration, it can be used in the form of ointments, creams, and the like. Ointments can be mixed with oils and petroleum jelly, and creams can be mixed with emulsifiers. These various preparations can also be added with other permeabilizing agents, preservatives, preservatives, wetting agents, buffering agents, emulsifiers, dispersants, stabilizers, etc. as required to make pharmaceutically acceptable carriers. In addition, these various preparations may be filtered by using a bio-retaining filter as required, and treated with a bactericide or the like to make them sterile. The amount of the pyrrolopyridinone derivative represented by the formula (I) and the medically tolerable salt may vary depending on the type of disease, the method of administration, the symptoms of the patient, age, sex, weight, etc., and it is usually Oral administration is about 1 to 500 mg per person per day. Intravenous, subcutaneous, intramuscular, and transdermal parenteral administration is about 0.1 to 100 mg per person per day. Examples The present invention will be specifically described below based on examples. However, the present invention is not limited to these examples. The compound number -262- 200526665 (258) attached to each compound in the following examples corresponds to the compound number attached to the compounds listed in the above table as preferred specific examples. In addition, regarding the data of the compounds synthesized in the following examples, "HP LC storage time" indicates a compound retention time (in minutes) in HPLC analysis under the following analysis conditions.

HPLC (high performance liquid chromatography) analysis conditions system: Hewlet-Packard 1100 HPLC column Cadenza CD-C18 (manufactured by imtakt) 100mmx4.6mm0 Solvent: A: H20 / acetonitrile = 95/5 (0.05% trifluoride Acetic acid) B ·· H20 / acetonitrile = 5/95 (0.05% acetic acid trifluoride) Flow rate: 1.0mL / min Gradient: 〇-1 minute solvent B 1 0% solvent A 9 0% 1-14 minutes solvent B 1 0 % — 100% Solvent A 90% -0% 14-16 minutes Solvent B 1 0% Solvent A 0% Purity calculation: UV absorption (254ΠΠ1) area. /.

Reference Example 1 Synthesis of (cyclopropylhydroxymethylene) methane-l, b dinitrile

Tetrahydrofuran (150ml) suspension containing sodium hydride (H.49g) -263- 200526665 (259) was cooled to 0 ° C. A solution of malononitrile (15.8 g) in tetrahydrofuran (50 ml) was added dropwise over 1 hour. After the reaction mixture was stirred at room temperature for 1 hour, the reaction mixture was cooled to 0 ° C., and a solution of cyclopropylcarbonyl chloride (25.0 g) in tetrahydrofuran (50 ml) was added dropwise over 80 minutes. After the reaction mixture was stirred at room temperature for 49 hours, water (50 ml) was added to the reaction solution. The solvent was removed by distillation under reduced pressure, and ethyl acetate (200 ml) and lmo 1/1 hydrochloric acid (270 ml) were added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated common salt water and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product (40.9 g) of the title compound. The NMR data of this compound are shown below. 1 H-NMR (400 MHz, CDCI3) δ (ppm): 1 · 1 0 -1 · 2 2 (m, 4 Η), 2.10-2.22 (m, 1 Η), 4.27 (s, 3 Η). Similarly, malononitrile and 3-chlorothiophene-2-carbonyl chloride were used to obtain [(3-chloro (2-thienyl)) hydroxymethylene] methane-1,1-dinitrile. The NMR data and ESI / MS data of this compound are shown below. 1H-NMR (400MHz »CD3OD) 5 (ppm): 6 · 9 2 (d, J = 5 · 1, 1 Η), 7.5] (d, J = 5.4, 1 Η) ESI / MS m / e: ( M +, Hf, C8H3C1N20S) Reference Example 2 Synthesis of (cyclopropylmethoxymethylene) methane-1,1-dinitrile

^ CN H3C-O CN A suspension of tetrahydrofuran (100 m 1) containing sodium hydride (2.6 g) was cooled to 0 ° C. A tetrahydrofuran (60 ml) solution containing (1-hydroxy-2.phenylmethylene-264-200526665 (260)) methane-1,1. Dinitrile crude (14.5 g) was added dropwise over a period of 30 minutes. After the reaction mixture was stirred at room temperature for 20 minutes, it was cooled to 0 ° C, and a solution of dimethyl sulfate (13. 7 g) in tetrahydrofuran (40 ml) was added dropwise over 1 hour. After heating under reflux for 2 hours, the mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. To the residue were added ethyl acetate (100 ml) and a saturated aqueous sodium hydrogen carbonate solution (100 ml), followed by extraction with ethyl acetate. After the organic layer was washed with saturated brine, the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1) to obtain the title compound (6.8 g, yield 54%). The NMR data of this compound are shown below. iH-NMRMOOMHz, CDC13) 5 (ppm): 1 · 1 0 -1,2 2 (m, 4 Η), 2.10-2.22 (m, 1 Η), 4.27 (s, 3 Η). Reference Example 3 Synthesis of methyl 3-amino-l- {2-[(third-butoxy) carbonylamino] ethylbuzocyano-5-cyclopropylpyrrole-2-carboxylic acid methyl ester

N- (2-aminoethyl) carbamic acid tert-butyl ester (6.3g) is added to the solution containing (methoxycyclopropylmethylene) methane-1,1-dinitrile (8.7g) The solution was stirred in acetonitrile (150 ml) at room temperature for 10 minutes. Anhydrous carbonic acid (38.5 g) and methyl bromoacetate (; n. 2 ml) were added and heated under reflux for 6 hours. After cooling to room temperature, it was left to stand 'and the supernatant liquid was separated by decantation. The solvent was removed by distillation under reduced pressure -265- 200526665 (261). The residue was concentrated and the solid portion left after pouring was added. Ethyl acetate and water were added, and extracted three times with ethyl acetate. The organic phase was washed with water and saturated brine, and then dehydrated with anhydrous magnesium sulfate. The sulfuric acid meter was filtered off, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1) to obtain the title compound (17.5 g, yield 85%). The ESI / Ms data of this compound are shown below. ESI / MS m / e: 3 49.1 (M + + H, C17H24N404) In the same manner as in Reference Example 2 and Reference Example 3, [(3-chloro (2-thienyl)) hydroxymethylene] methane-1, 1-dinitrile was used as a raw material to synthesize 3-monthlyl (third butoxy) hydroxyamino] ethylbu (3-chloro (2-thienyl) cyanopyrrole-2-carboxylic acid methyl ester. As shown below ESI / MS data of this compound. ESI / MS m / e: 42 5 · 2 (M + + H, C18H21C1N404S) Reference Example 4 (Third Butoxy) -N- [2- (7-cyano Synthesis of Alkoxy-6-Cyclopropyl (3-Pyrrolidine [3,2_d] pyrimidin-5_yl) ethyl] fluorenamine

Add; K-amino- 丨-{2-[(third-butoxy) carbonylamino] ethyl 4-methyl 4-cyano-5-cyclopropylpyrrole-2-carboxylic acid methyl ester (17.4g) and methyl Rhenium hydrochloride (-266- 200526665 (262) 104.lg) in 2-propanol (360ml) was heated under reflux for 45 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure. Water was added to the residue, and the resulting solid matter was collected by filtration and washed thoroughly with water. This solid was recrystallized (ethanol / ethyl acetate / hexane = 1/2/1) to obtain the title compound (9.8 g ', yield 57%). The ESI / MS data of this compound are shown below. ESI / MS m / e: 3 62 · 1 (M + + Η, C17H2iN5 03) Similarly, 3-amino-l- {2-[(third-butoxy) carbonylamino] ethyl group 5 was used. -(3-Chloro (2-thienyl))-4-cyanopyrrole-2 · carboxylic acid methyl ester 'synthesized to obtain (third butoxy) -N- {2- [6 · (3-气 (2 -Thienyl))-7-cyano-4-oxy [3-hydropyrrole [3'2-d] pyrimidin-5-yl]] ethyl} fluorenamine. The ESI / MS data of this compound are shown below. ESI / MS m / e: 420.2 (M + + Η, C18H18C1N 5 03 S) Reference Example 5 Synthesis of 3 -oxy-2- (3-pyridyl) propionitrile hydrochloride

HCI Ο Ο was added dimethylformamide dimethyl acetal (123.6 g) in a toluene (100 ml) solution containing 3-pyridinylacetonitrile (40.8 6 g), and heated to reflux for 4 hours. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate), and the obtained brown solid was washed with ethyl acetate to obtain a colorless solid (46.93 g). Water (-267-200526665 (263) 40 ml) and concentrated hydrochloric acid (24.50 ml) were added to a suspension of tetrahydrofuran (300 ml) containing the reaction product (20.37 g), and the mixture was stirred at 50 t for 4 hours. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure. The residue was dried in the air to obtain the refined product of the title compound (3 0.1 2 g). This product was used for subsequent reactions without further purification. The ESI / MS data of this compound are shown below. ESI / MS m / e: 147.1 (M + + H, C8H5N20 HC1) Reference example 6 3-(((1Z) -2 -cyano-2- (3 -pyridinyl) ethane) ([methoxy Synthesis of Ethylcarbonyl) Methyl] Amino} Ethyl Propene

Add crude 3-oxy-2- (3-pyridyl) propionitrile (7.826 £) to ethyl 3-{[((methoxycarbonyl) methyl] amino} propionate) (6.720 g ) In acetic acid (30 m I) solution, and stirred at 80 ° C for 2 days. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure. The residue was diluted with water, neutralized with sodium carbonate, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dehydrated with sodium sulfate. After sodium sulfate was filtered off, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/3) to obtain the title compound (7.52 21 g, yield 83%). The ESI / MS data of this compound are shown below. -268- 200526665 (264) ESI / MS m / e: 318 · 2 (M + + Η, Ci6Hi9N3 04) Reference Example 7 3- [3-Amino-2- (methoxycarbonyl) -4- (3 -Pyridyl) pyrrolyl] ethyl propionate

Add 1,8-diazabicyclo [5,4, 〇] -7-undecene (3.590g) to 3-{((1Z) -2-cyano-2- (3-pyridyl) ethylene ) [(Methoxycarbonyl) methyl] amino} propionic acid ethyl ester (6.236 g) ethylene glycol dimethyl ether (50 ml), and stirred at 60 ° C overnight. After the reaction solution was cooled to room temperature, acetic acid was added to neutralize it, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/5) to obtain the title compound (4.38 g, yield 70%). The NMR data and ESI / MS data of this compound are shown below. H-NMR (400 MHz, DMSO-d6) (5 (ppm): 1 · 1 0 -1 · 1 8 (m, 3 Η), 2 74 (t, J = 6.8 25 2 H), 3.77 (s? 3H) 5 3 · 9 9-4 · 0 7 (m 5 2 H), 4-38 (t? J = 6.8 45 2H)? 7.46 (s5 1 H), 7 · 8 5 (dd, J = 5 · 7 4 5 J = 7 · 9 4 ,, Uh 8.36 (d, J = 8.0 8 9 1 H)? 8.60 (d? J = 5.40? 1H)? 8.84 (s, 1H) ESI / MS m / e: 318.2 (M + + H, C16Hi9N304) -269- 200526665 (265) Reference Example 8 Synthesis of (cyclopropylhydroxymethylene) methane-1-(3-pyridyl) -1-nitrile

HO CN 500ml eggplant-shaped flask was placed with 3-pyridineacetonitrile (13.0g, 110mmol), and then added with tetrahydrofuran (150ml), while stirring at 0 ° C, n-butyllithium (2.6M The solution was 44 ml, 1 14 mm (0.01 mm), stirred at 0 ° C for 30 minutes, and then stirred at 40 ° C for 30 minutes. After cooling to 0 ° C, a tetrahydrofuran (30 ml) solution containing cyclopropanecarbonyl chloride (10.45 g, 100 mmol) was added dropwise while stirring. After stirring at room temperature for 1 hour, a saturated ammonium chloride aqueous solution (300 ml) was added to the reaction Separated in liquid. The aqueous layer was extracted with ethyl acetate (100 ml), and the organic layer was washed twice with saturated brine (300 ml). The organic layer was dehydrated with magnesium sulfate, dried, filtered, and concentrated to obtain a concentrated residue (18.25 g). Add acetonitrile (30ml) directly to the concentrated residue to filter off the insoluble portion, and wash with acetonitrile (20ml) to obtain the crude product of the title compound (5.17g, yield 28%). The NMR data of this compound are shown below. ] H-NMR (400MHz, DMSO-d6) 5 (ppm): 0.64 (m, 4H), 2.24 (m, 1H) 5 2.5 0 (brds, 1H), 7.70 (dd? J = 5.4Hz5 J = 8.6Hz5 1H), 8.11 (d, J = 5.4Hz, 1H), 8.21 (d? J = 8.6Hz, 1H), 9 · 12 (brds5 1 H). ESI / MS m / e: 187.1 (M + + H, C]] H] 〇N20) -270- 200526665 (266) Reference Example 9 (Cyclopropyl-p-methylsulfoxaloxymethylene) Synthesis of -1- (3-pyridyl) -1-nitrile

(Cyclopropylmethylidene) methane-1- (3-pyridyl) -benzonitrile (4.51§, 24.3111111〇1) and p-toluenesulfonic anhydride (9.14g, 28 mm), and dichloromethane (100 ml) was added, and triethylamine (4.8 ml, 34.5 mmol) was added dropwise while stirring at room temperature, followed by stirring at room temperature for 2 hours. After the completion of the reaction, 'water (50 ml) was added to the reaction solution for separation. The aqueous layer was extracted with dichloromethane (2), and the organic layer was washed once with a saturated aqueous sodium hydrogen carbonate solution (50 ml), and then washed twice with water (50 ml). The organic layer was dehydrated with magnesium sulfate, dried, filtered, and concentrated to obtain a purified product of the title compound (8.47 g, yield 100%). The NMR data and ESI / MS data of this compound are shown below. ] H-NMR (270MHz, CDC13) δ (ppm): 1.10-1.32 (m5 4H), 2.40 (s; 3H); 2.15-2.42 (m? 1H)? 7.05 (m? 3H)? 7.40 (m? 2H )? 7 · 6 0 (m, 1 H), 8 · 4 0 (m, 2 H). ESI / MS m / e: 341 · 〇 (M + + 18, C18H〗 6N2〇3S) Reference Example 1 〇3-amino group 4-(3 · H0O group) -5 -cyclopropyl D (t. -2-Synthesis of Residual Ethyl Ester -271-200526665 (267)

A 200ml eggplant-type flask was charged with (cyclopropyl-p-tosylsulfonyloxymethylene) methane-1- (3-pyridyl) -benzonitrile (7.764g, 22.8mmol), and ethanol (70ml) was added. And tetrahydrofuran (35 ml), and diethylaminomalonate hydrochloride (5.0 8 g, 24 mmol) was added under stirring at 0T. Next, an ethanol solution (35 ml) containing sodium ethoxide (5.43 g, 80 ml) was added dropwise, and the mixture was stirred at 0 ° C for 1 hour. After the reaction was completed, the solvent was concentrated under reduced pressure, and water (150 ml) and ethyl acetate (100 ml) were added to the concentrated residue for separation. The aqueous layer was extracted with ethyl acetate (50 ml), and the organic layer was washed once with water (100 ml), and washed three times with a saturated saline solution (50 ml). The organic layer was dehydrated with magnesium sulfate, dried, filtered, and concentrated to obtain a refined product (3.90 g). It was then purified by silica gel column chromatography (silica gel), 〇〇g; elution solvent: hexane / ethyl acetate = 4/1-〇 / 1, to obtain the title compound (1.07 g, recovered Rate 17%). The NMR data and ESI / MS data of this compound are shown below. ] H-NMR (2 70 MHz, CDCls) (5 (ppm): 0.60-0.95 (m, 4 Η), 1.30 (m, 1 Η), 1.36 (t, J = 7.0 Hz5 3 Η), 4.15 (q, J = 7.0Hz, 2Η), 4.35 (brds5 2H), 7.15 (m, 1H), 7.75 (m, 1H), 8.50 (m, 1H), 8.75 (s, 1H). ESI / MS m / e: 272 · 1 (M + + Η, C15H17N3〇2) Reference Example 1] N- {2- [4-chloro-6- (3-chloro (2-thienyl))-7-iodine- 200526665 ( 268) Synthesis of pyrrolidine [3,2-d] pyrimidin-5-yl] ethylpyridine 2,2,2-trifluoroacetamide

Contains Ν · {2 · [6- (3-chloro (2-thienyl))-7-iodo-4-oxy (3-hydropyrrole [3,2-d] pyrimidin-5-yl)] ethyl A solution of 2,2,2-trifluoroacetamidamine (3.3 3 mg) in phosphonium chloride (3.0 ml) was stirred at 1 1 (TC for 2 hours. The reaction mixture was cooled to room temperature, and then distilled under reduced pressure. Remove excess phosphorous chloride. Dry the residue in vacuo to obtain the refined product of the title compound. The obtained refined product can be used directly for subsequent reactions without purification. The ESI / MS data of this compound is shown below. ESI / MS m / e: 5 3 5.2 (M + + H, C14H8Cl2F3IN4OS) Reference Example 12 N- {2- [7-Bromo-4-chloro-6- (3-chloro [2-thienyl]) pyrrolo [3,2-d] Synthesis of Pyrimidin-5-yl] ethylbuthyl 2,2,2-trifluoroacetamide

In the same manner as in Reference Example 11, N- {2- [7-bromo-4-chloro-6- (3- -273- 200526665 (269) chloro [2-thienyl])-4-oxy (3 -Hydropyrrole [3,2-d] pyrimidin-5-yl] ethyl} -2,2,2-trifluoroacetamidamine to obtain a purified product of the title compound. The ESI / MS data: ESI / MS m / e: 48 9.0 (M + + H ^ C 4 Η 8 B r C 12 F 3 N 4 〇S) Example 13 N- {2- [4,7 -dichloro · 6- (3-chloro (2-thienyl))

Synthesis of pyrrolidine [3,2-d] pyrimidine · 5-yl] ethyl} -2,2,2-trifluoroacetamide

Following the same method as in Reference Example 11, N- {2- [7-chloro-6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrole [3,2-d] Pyrimidine-5 -yl)

] Ethylbuthyl 2,2,2-trifluoroacetamide, to give a purified product of the title compound. The ESI / MS data of this compound are shown below. ESI / MS m / e: 443.4 (M + + H, C14H8Cl3F3N4〇S) Reference example 1 4 N-(2-{7-[(1 E)-1 -aza-2 · (dimethylamino)) ethylene Synthesis of] -4-chloro-6- (3-chloro (2-thienyl)) pyrrole [3,2-called pyrimidine-5 ~ yl} ethyl) (4-fluorophenyl) fluorenamine -274- 200526665 (270) CH3 h3c-n.

In the same manner as in Reference Example 11, N-(6-(3 -chloro (2-thienyl))-5- {2-[(4 · fluorophenyl) carbonylamino] ethyl 4-oxy ( 3-Hydropyrrole [3,2-d] pyrimid-7-yl))-2,2,2-trifluoroacetamidamine (1.09 g) to obtain a purified product of the title compound (0.87 g ). The NMR data and ESI / MS data of this compound are shown below.丨 H-NMR (400MHz, DMSO-d6) (5 (ppm): 2.81 (brs5 1H), 2.97 (brs 1H) 5 3.2 8 (s; 2H)? 3.3 7-3.4 5 (m? 2H) 5 7.1 7 -7.2 7 (m5 3 H), 7 · 5 5-7.6 8 (m, 2 H), 7.8 6 (d, J = 5 · 4, 1 H) 5 8.3 BU 8 · 3 8 (m, 1 H) , 8.61 (s5 1 H), 8.75 (s, 1 H). ESI / MS m / e: 5 05.4 (M + + H, C22H19C12FN60S) Example 1 5- {2-[(third butoxy) _Aminoamino] ethylbu 6- (3-chlorothienyl)) oxy-3-hydrocarbazine [3'2-d] ^ n-7-7-fluorenamine (compound number: 9 5 0) Synthesis-275- 200526665 (271)

Dissolve 3.0g of (third butoxy) -N- {2- [6- (3-chloro (2-thienyl))-7-cyano-4-oxy (3-amino D than slightly [ 3,2-d] anuridine-5-yl)] ethyl} fluorenamine in 1001111 ethanol, and 5111 sodium hydroxide aqueous solution of 20111 was added. Add 30 ml of a 30% hydrogen peroxide solution over 20 minutes with stirring. After stirring at 45 ~ 50 ° C for 24 hours, add 20ml of 30% hydrogen peroxide aqueous solution and stir at 45 ~ 50 ° C for 24 hours. After concentration, it was neutralized with 1M hydrochloric acid, and the precipitated white precipitate was filtered and washed with water. Drying under reduced pressure gave the title compound (2.68 g, yield 86%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 7.2 (minutes) 1 H-NMR (270MHz ^ DMSO-d6) 5 (ppm): 1.26 (s, 9H), 3.2- 3.5 (m, 2H), 3.8-4.0 (m, 1H), 4.4 -4.6 (m, 2H), 6.5-6.6 (m, 1H); 7.17 (d, 1H, J = 4.6Hz), 7.2-7 · 3 (ιη, 1H), 7.91 (d, 1H, J = 5.4Hz ), 8.0-8.1 (m, 1H), 12.4-12.5 (m 1H). ESI / MS m / e: 438.3 (M + + H, C] 8H2C1N504S) Example 2 5- {2-[(Third butoxy) carbonylamino] ethylbulf-cyclopropyl)- Cooperation of 4 -oxy-3 -pyridoxine [3,2 -d] Biddin-7 -amidamine (compound number: 8 9 8) -276- 200526665 (272)

H2N〇C

Following the same method as in Example 1, (third butoxy) -N- [6-cyclopropyl-7-cyano-4-oxy (3-hydropyrrolo [3,2-d] pyrimidine-5) was used. -Yl)] ethyl} amidamine to give the title compound. The ESI / MS data of this compound are shown below. ESI / MS m / e: 3 62 · 1 (M + + Η, C17H23N5 04) Example 3 N- {2- [7 · Amine-6- (3-chloro (2-thienyl))-4- Synthesis of 3- (3-Hydropyrrole [3,2-d] pyrimidin-5-yl)] ethyl} (Third-butoxy) amidamine (Compound No. 959)

1 10 mg of 5- {2-[(third butoxy) carbonylamino] ethyl 6- (3-chlorothienyl)) 4-oxy-3-hydropyrrole [3, 2-d] pyrimidine-7-amidamine in 7.5 ml of a 1 M aqueous sodium hydroxide solution. Add 1 3 5 mg of benzyltrimethylammonium tribromide and stir for 1.5 hours. After 1 M hydrochloric acid was added to make it acidic, it was washed with ethyl acetate. The aqueous layer was made basic with sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate -277- 200526665 (273). After filtration and concentration, the solvent was extracted with silica gel 1. The house: ethyl acetate = 1: compound (72 mg, yield 70%). And ESI / MS data. JH-NMR (270MHz, CDC13) δ 3.5 (m, 2Η), 4.3-4.5 (m, 2Η), J = 5.4Hz)? 7.54 (d? 1H, J = 5., 10 · 1 (m5 1 H) Column chromatography (silica gel, 15 g; wash 1 ~ 10: 1), the title Θ shows the NMR data (pPm) of this compound: 1.32 (s, 9H), 3.3-4 · 9, S.〇 (m, 1H), 7.1 l (d5 1H, 2), 7.79 (brs, 1H)? 10.0-

ESI / MS m / e: 410 · 3 (M + + Η, Cl7t}, cin5o3s) Example 4 N- {2- [7-Amine vapor group] _4_oxy (3 · hydropyridine (third butyl (Oxy) amidine (Hydroxypyrene [3,2-d] pyrimidin-5-yl)} ethase} Compound number: 903) h3c h3c

ΝΗ

The title compound was obtained according to the same method as in Example 3 using ethylamino] ethylbu 6-cyclopropyl) -4 and pyrimidine-7-amidine according to ESI / MS data. W-NMRmOMHz, CDC13) 5 1.2 (m5 5H) 5 3.4 (brs; 2H) 5 3.5. 5.6 (brs, 1H), 7.8 (brs, 1H) 〇 ~ S, {2-[(third butoxy) Carbonyl_-3-hydropyrrole [3,2-d] The NMR number (pPm) of this compound is shown below: 1.34 (s, 9H) 5 0.8- ° (m5 3H), 4.5-4.6 (m5 2H)?

I 200526665 (274) ESI / MS m / e: 3 3 4 · 1 (M + + Η, C16H23N50) Example 5 (Third butoxy-N- {2- [7-amino-6- Synthesis of (3-Chloro (2-thienyl))-4-oxy (3-hydropyrrole [3'2-d] pyrimidin-5-yl)] ethyl} fluorenamine (compound number: 945)

Obtained 30 mg of N- {2- [7-amino-6- (3-chloro (2-thienyl))-4-oxy (3-hydroaramidol [3,2-d] pyrimidine-5- Group)] ethyl} (third-butoxy) fluorenamine, after adding 1 ml of bromoform, then add 50 μΐ of isoamyl sulfinate. After stirring at 7 ° C for 4 hours, saturated brine was added and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Thin layer chromatography on silica gel (developing solvent, ethyl acetate) was provided, and The title compound (15 mg, yield 43%) was obtained. The HP LC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 9 · 5 (minutes) 1H-NMR (270MHz »CDC13) (5 (ppm): 1.31 (s, 9H), 3.3 · 3.5 (m, 2Η), 4.2-4.3 (m, 1Η), 4.5-4.7 (m, 1Η), 4 · 7-4 · 9 (η, 1H), 7.13 (d, 1H, J = 5.7Hz), 7.60 (d, 1H5 J = 5.4Hz) 5 7.94 (d, 1H, J = 3.0Hz). ESI / MS m / e: 4 7 5 · 2 (Μ + + Η, C17H] 8BrClN4 03 S) -279- 200526665 (275) Example 6 (Third butoxy-N- {2- [7-bromo-6-cyclopropyl] -4-oxy Synthesis of (3-Hydropyrrolo [3,2-d] pyrimidin-5-yl)} ethyl) fluorenamine (compound number: 2511) Bγ h3c h3c

ch3 ο N- {2- [7-Amino-6-cyclopropyl] -4-oxy (3-hydropyrrolo [3,2-d] pyrimidin-5-yl) was used in the same manner as in Example 5. } Ethyl} (third butoxy) fluorenamine to give the title compound. The HP LC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 8.5 (minutes) j-NMRUTOMHz, CDC13) δ (ppm): 1.3-1 (s5 9H), 1.1- 1.3 (m, 5 Η), 3.5-3 · 9 (m, 3 Η), 4.5-4 · 9 (m, 2 Η), 5.-5 · 3 (brs,] H), 7.9 (s, 1 H) ESI / MS m / e: 3 9 7 · 1 (Μ + + Η, CI6H2IBrN4 02 S) Example 7 (Third-butoxy) -N- {2- [6- (3-chloro (2-thienyl))-7-iodo-4-oxy (3- Synthesis of pyrrolidine [3,2-d] pyrimidin-5-yl] ethyl} fluorenamine (compound number: 946) -280- 200526665 (276)

N- {2- [7-amino-6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrolo [3,2-d] pyrimidin-5-yl) )] Ethyl} (third butoxy) fluorenamine, after adding 7 ml 1 of diiodomethane iodide, 822 μΐ of isoamyl nitrite was added. After stirring at 70 ° C for 4 hours, saturated brine was added and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Silica gel chromatography (eluent, hexane · ethyl acetate = 5: 1--0: 1) was provided to obtain the title compound (694 mg, yield 55%). The NMR data and ESI / MS data of this compound are shown below. HPLC retention time = 9.6 (minutes) 1H-NMR (270MHz, CDC13) δ (ppm): 1.32 (s, 9H) 5 3.3- 3.5 (m, 2 H), 4 · 2-4 · 3 5 (m , 1 H), 4 · 6-4.7 5 (m, 1 H), 4 · 8-5 · 0 (m, 1H), 7.M (d, 1H, J = 5.4Hz), 7.59 (d, 1H , J = 5.7 Hz), 7.95-8.05 (m, 1H). ESI / MS m / e: 521.3 (M + + H, CI7H18C1IN503 S) Example 8 (Third butoxy-N- {2- [7-iodo-6-cyclopropyl] -4-oxy (3 -Synthesis of pyrrolidine [3,2-d] pyrimidin-5-yl)} ethyl) fluorenamine (compound number: 896) -281-200526665 (277) H3C h3c

CH3 O Using N- {2- [7-amino-6-cyclopropyl] -4-oxy (3-hydropyrrole [3,2-d] pyrimidin-5-yl) in the same manner as in Example 7 } Ethyl} (third butoxy) fluorenamine to give the title compound. The HP LC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 8.7 (minutes) 1 H-NMR (2 70 MHz, CDC13) δ (ppm): 1.31 (s, 9H), 1.0-1.3 (m, 5H), 3.5-3.8 (m, 3H ), 4.7-4.9 (m, 2H), 5.2-5.3 (brs, 1H) 5 7.9 (s5 1H) ESI / MS m / e: 445.4 (M + + H, C) 6H21IN4 03) Example 9 (third Butoxy) -N- {2- [7-chloro-6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrole [3,2-d] pyrimidine-5- )] Synthesis of Ethyl} amidamine (Compound No. 944)

20 mg of N- {2- [7-amino-6- (3-chloro (2-thienyl))-282- 200526665 (278) 4-oxy (3-hydropyrrolepyrene [3,2- d] pyrimidin-5-yl)] ethyl} (third butoxy) fluorenamine, after adding 2 ml of tetrachlorocarbon, then 34 μΐ of isoamyl nitrite. After refluxing for 40 hours, saturated brine was added and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Silica gel thin layer chromatography (developing solvent, ethyl acetate) was provided to obtain the title compound (5 mg, yield 24%). The Η P L C retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 9.4 (minutes)] H-NMR (270MHz, CDC13) 5 (ppm): 1.32 (s, 9Η), 3.3-3.5 (m, 2H), 4.15-4.4 (m, 1 H)? 4.6-4.75 (m, 1H), 4.8- 4.95 (m? 1H)? 7.13 (d? 1H? J = 5.4Hz)? 7.60 (d5 1H? J = 5.4Hz), 7_98 (brs; 1 H). ESI / MS m / e: 429.4 (M + + H, C17H18C12N403 S) Example 10 (Third butoxy) -N- {2- [6- (3-chloro (2-thienyl))-4- Synthesis of oxy (3 -hydropyrrole [3 '2-d] pyrimidin-5-yl)] ethyl} fluorenamine (compound number: 9 4 3)

Obtained 1 ^-{2- [7-amino-6- (3-chloro (2-thienyl)) · 4-oxy (3-hydropyrrole [3,2-d] pyrimidine-5] -Yl)] ethyl} (third-283-200526665 (279) butoxy) fluorenamine, 2 ml of tetrahydrofuran was added, and then 50 μΐ of isoamyl nitrite was added. After stirring at 5 ° C for 3 hours, saturated brine was added and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Thin layer chromatography on silica gel (developing solvent, ethyl acetate) was provided, and The title compound (8 mg, yield 55%) was obtained. The NMR data and ESI / MS data of this compound are shown below. HPLC retention time = 8.4 (minutes) 1H-NMR (270 MHz, CDC13) (5 (ppm): 1.3 1 (s? 9H), 3.3-3.5 (m, 2H), 4.4-4.6 (m, 2H), 5.01 (brs, 1H), 6.66 (s, 1H), 7.07 (d, 1H, J = 5.4Hz) , 7.49 (d, 1H, J = 5.1Hz), 7.93 (brs, 1H), 1 1.2-1 1.3 (m, 1H). ESI / MS m / e: 3 9 5 · 2 (M + + Η, C17H19ClN4 〇3S) Example 1 1 5-(2 -Aminoethyl) -6-(3 -chloro (2-thienyl))-7 -iodine-3_hydropyrrolo [3,2-d] pyrimidine-4 -Synthesis of Ketone Hydrochloride (Compound Number: 206)

Dissolve 331mg of (third butoxy) · N- {2_ [6 ~ (3-chloro (thienyl))-7-iodo-4-oxy (3-hydrogenated ItIt 骈 [3 '2-d ] ANS-D-5-5-yl)] ethyl} fluorenamine in a mixed solution of 0.5 m 1 of methanol and 5.0 m 1 of 1,4. Dioxane, and 4 m / 1 of hydrochloric acid was added / 1, dioxane solution (0.64ml) 200526665 (280), stirred at 6 ° C for 2 hours. After cooling the reaction mixture to room temperature, the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure to obtain the title. Compound (334 mg, yield, quantitative). The ESI / MS data of this compound is shown below. ESI / MS m / e: 421.2 (M + + H, C12H10C1N4OS HC1) Example 1 2 5-(2 -Amine ethyl Synthesis of 7-bromo-6- (3-chloro (2-thienyl))-3-hydropyrrole [3,2-d] pyrimidin-4-one hydrochloride (compound number: 2 05)

NH2 HCI Using (third butoxy) -N- {2- [7-bromo-6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrole) in the same manner as in Example 11.骈 [3 '2-d] pyrimidin 5-yl)] ethyl} amidamine to synthesize the title compound. The ESI / MS data of this compound are shown below. ESI / MS m / e: 3 7 5.0 (M + + Η, C12H1 () BrClN4OS HC1) Example 13 5- (2-Aminoethyl) -7-chloro-6- (3-chloro (2- Synthesis of thienyl))-3 -pyrrolidine [3,2-d] pyrimidin-4-one hydrochloride (compound number: 204) -285- 200526665 (281)

(Third-butoxy) -N- {2_ [7_ 6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrole [3,24] was used in the same manner as in Example U. Pyrimidine-5 -yl)] ethyl} amidamine to synthesize the title compound. The ESI / MS data of this compound are shown below. ESI / MS m / e: 329 · 4 (M + + Η, C12H10C12N4OS HC1) Example 14 N- {2- [6- (3-chloro (2-thienyl))-7-bowl-4 -oxyl Synthesis of (3-Hydropyrrole [3,2-d] pyrimidin-5-yl)] ethylpyrene 2,2,2-trifluoroacetamidamine (Compound No. 320)

Add trifluoroacetic anhydride (595mg) to 5- (2-aminoethyl) -6- (3- (2-thienyl) -7 · iodo-3-hydropyrrolo [3,2-d] pyrimidine- After a solution of 4-ketohydrochloride (259 mg) in tetrahydrofuran (5.0 ml), triethylamine (1.2 ml) was slowly added dropwise. After the reaction mixture was stirred at room temperature for 2 hours, methanol was added to stop the reaction. The solvent was distilled off under reduced pressure, and water and ethyl acetate were added to the residue, and extracted three times with ethyl acetate. The organic layer was washed with saturated food -286- 200526665 (282), washed with brine, dried over anhydrous magnesium sulfate, and filtered through anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure to obtain a purified product (35 mg) of the title compound. The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 9.1 (minutes) 1H-NMR (400MHz, DMSO-d6) &lt; 5 (ppm): 3.45 (m, 2H), 4.16 (m, 1H), 4_61 (m, 1H), 7.30 (m, 1H), 7.93 (m, 1H), 8.02 (m5 1H), 9.37 (m, 1H), 12.29 (brs, 1H). ESI / MS m / e: 517.2 (M + + H, C14H9ClF3N4〇2S) Example 15 N- { 2- [7-bromo-6 · (3-chloro (2-thienyl))-4-oxy Synthesis of (3-Hydropyrrolo [3,2-d] pyrimidin-5-yl)] ethyl} -2,2,2-trifluoroacetamidamine (Compound No .: 3 1 9)

5- (2-Aminoethyl) -7-bromo-6- (3-chloro (2-thienyl))-3-hydropyrrole [3,2-d] pyrimidine-4 was used in the same manner as in Example 14. -Ketone hydrochloride to synthesize the title compound. The ESI / MS data of this compound is shown below. ESI / MS m / e: 471.1 (M + + H, C14H9BrClF3N402S) -287- 200526665 (283) Example 16 Ν- {2- [7 · 气 -6- ( 3-Ga (2-fluorenyl))-4-oxy (3-hydropyrrole [3,2-d] pyrimidin-5-yl)] ethyl} -2,2,2-trifluoroacetamidine Synthesis of Amine (Compound No. 318)

5- (2-Aminoethyl) -7-chloro-6- (3 · chloro (2-thienyl))-3-hydropyrrolo [3,2-d] pyrimidine-4 was used in the same manner as in Example 14. -Ketone hydrochloride to synthesize the title compound. The ESI / MS data of this compound is shown below. ESI / MS m / e: 42 5.4 (M + + H, C14H9C12F3N402S) Example 17 N- {2- [6- (3-chloro (2-thienyl))-7 -Iodine-4-oxy

Of 3- (3-Hydropyrrolo [3,2-d] pyrimidin-5-yl)] ethyl} (4-fluorophenyl) fluorenamine (compound number: 3 4 4)

Add 4-fluorobenzene (23 mg) to fluorenyl chloride (5-mg-aminoethyl) -6 · -288- 200526665 (284) (3-chloro (2-thienyl))-7-iodine-3 · Pyrrolidine hydrochloride [3,2-d] pyrimidin-4-one hydrochloride (33 mg) in N, N-di &gt; methylformamide (2.0 ml) solution, and after stirring at room temperature for a while, 'Add three Ethylamine (2.0ml) ''

Stir at room temperature for 2 hours. Water (0.2 m 1) 'was added to the reaction solution, and the mixture was stirred overnight at room temperature. The solvent 'residue was distilled off under reduced pressure and purified by fractional distillation HPLC to obtain the title compound (22 mg, yield 55%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 9.1 (minutes) 1H-NMR (400MHz ^ DMSO-d6) δ (ppm): 3.52 (m, 2H), 4.24 (m, 1H), 4.63 (m, 1H), 7.19-7.26 (m, 3H), 7.70-7.74 (m, 2H), 7.88-7.92 (ιη, 2H), 8; 45 (m, 1H), 12.24 (brs, 1H). ESI / MS m / e: 5 4 3.3 (M + + H, C19H13ClFIN4〇2S) Example 18 6- (3-chloro (2-thienyl))-7-iodo-5- [2- (quinazoline Synthesis of 4--4-aminoamino) ethyl] -3-hydropyrrole [3,2-d] pyrimidin-4-one (compound number: 8 1) Φ

Add triethylamine (16mg) to 5- (2-aminoethyl) -6- (3-chloro (2-thienyl))-7-iodo-3 · pyrrolidine hydrochloride [3,2-d] pyrimidine -4-ketohydrochloride (36 mg) and 4-chloro D quinazoline (10 mg) in N, N-dimethylformamidine-289- 200526665 (285) amine (2.0ml) solution at 70 ° C Stir for 2 hours. Add triethylamine (32 mg) and stir at 70 ° C for 2 hours. The reaction mixture was cooled to room temperature and purified by fractional HPLC to obtain the title compound (21 mg, yield 49%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC holding time = 6.9 (minutes) 1H-NMR (400MHz ^ DMSO-d6) (ppm): 3.95 (m, 2H) 5 4.48 (m, 1H), 4.87 (m, 1H), 7.12 (m, 1H) , 7.71-7.82 (m, 3H), 7.87 (brs, 1H), 8.00 (t, J = 7.7, 1H), 8.18 (d, J = 8.3, 1H), 8.60 (s5 1H), 9.91 (brs5 1H) , 12.24 (brs5 1H). ESI / MS m / e: 5 49.4 (M + + H, C20H14C1IN5OS). Example 19 N- (5- {2-[(Third butoxy) carbonylamino] ethyl 6- (3- (2-thienyl))-4-oxy (3-Aminopyrene [3 '2-d] pyrimidin-7-yl))-2,2,2-trifluoroacetamidine (Compound No .: 962) Synthesis

Triethylamine (2.71111) was added to the compound containing 1 ^ {2- [7-amino-6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrole [3,2-d ] Pyrimidin-5-yl-290- 200526665 (286))] ethyl} (tertiary butoxy) fluorenamine (1.60 g) in tetrahydrofuran (39 m 1) solution, then cooled to 0 ° C, slow Trifluoroacetic anhydride (1.35 ml) was slowly added dropwise, and the reaction mixture was stirred at room temperature for 1 hour, and then the reaction was stopped by the dropwise addition of saturated saline. Ethyl acetate was added to the solution and extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off under reduced pressure to obtain the title compound (1.97 g, yield, quantitative). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 8.7 (minutes)] H-NMR (400 MHz, DMSO-d6) (5 (ppm): 1.26 (s, 9H), 3.13 · 3.26 (m, 2H), 4.11 (brs5 1H), 4.49 (brs , 1H), 6.60_6.73 (m, 1H)? 7.2 3 (d? J = 5.4? 1 H), 7.8.8 (s, 1 H), 7 · 9 5 (d, J = 5.4, 1 H) , 10.86 (s, 1 H); 1 2.2 1 (brs, 1H). ESI / MS m / e: 5 06.4 (M + + H »C 19 H i 9 C 1 F 3 N 5 〇4 S) Example 20 N- [5- (2-Aminoethyl) -6- (3-chloro (2-thienyl))-4 -oxy (3-hydropyrrolo [3 '2-d] pyrimidin-7-yl )] Synthesis of 2,2,2-trifluoroacetamidine hydrochloride (compound number: 207)

N- (5- {2-[(Third-butoxy) aminoamino] ethyl group 6-291-200526665 (287) (3-chloro (2-thienyl))-4-oxo (3-Hydropyrrolo [3,2-d] pyrimidin-7-yl))-2'2,2-trifluoroacetamidamine (1.97 g) in methanol solution (13 ml) was cooled to Ot :, A 4 mol / l hydrochloric acid / 1,4-dioxane solution (26 ml) was added, and the mixture was stirred at room temperature for 4 hours. The solvent was distilled off under reduced pressure to obtain a purified product of the title compound (1.73 g). The ESI / MS data of this compound are shown below. ESi / MS m / e: 406.3 (M + + H, CmHhFsNsC ^ S · HC1)

Example 21 N-6- (3-chloro (2-thienyl))-5- {2-[(4-fluorophenyl) carbonylamino] ethyl} -4-oxy (3-hydropyrrole) Synthesis of [3,2-d] pyrimidin-7-yl)]-2,2,2-trifluoroacetamide (Compound No .: 345)

Contains N- [5- (2-aminoethyl) -6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrolo [3,2-d] pyrimidin-7-yl )] [2,2,2-trifluoroacetamidine refined product (1.73 g) in pyridine (39 ml) solution was cooled to 0 ° C '4-fluorobenzidine chloride (0.92 ml) was added, Stir at room temperature for 1 hour. Water (40 m 1) was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour to terminate the reaction. After adding common salt until the solution was saturated, it was extracted with ethyl acetate. The organic layer was washed with a mixed solution of saturated saline and [mol / 1] hydrochloric acid (9: 1), dried over anhydrous sodium sulfate, and then filtered. The solvent -292- 200526665 (288) was distilled off under reduced pressure, and then purified by silica gel column chromatography (hexane / ethyl acetate = 1/2-&gt; using only ethyl acetate) to obtain the title compound ( 1.60g, 78% yield in 2 stages). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HP LC retention time = 8.3 (minutes) 1 H-NMR (400MHz ^ DMSO-d6) (5 (ppm): 3 · 4 9-3 · 5 8 (m, 2 Η), 4.34 (brs, 1Η), 4.66 (brs, 1Η), 7.16 (d, J = 5.4, 1Η), 7.19 (t, J = 7.19 2H)? 7.6 5 -7.75 (m? 2H)? 7.83 (d, J = 5.4? 1H)? 7.88 ( s? 1H), 8.40-8.5 0 (m, 1H), 10.85 (s, 1H), 12.25 (brs, 1H). ESI / MS m / e: 528.4 (M + + H, C21H14C1F4N5 03 S) Example 22 (Third butoxy) -N- [2- [6- (3-chloro (2-thienyl))-4-oxy-7- (phenylfluorenylamino) (3-hydropyrrole [ 3,2-d] pyrimidin-5-yl)] ethyl] fluorenamine (compound number: 965)

Add triethylamine (0.69ml) to N- [2- [7-amino-6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrole [3,2] -d] pyrimidin-5-yl)] ethyl] (third butoxy) fluorenamine (0.41 g) in a tetrahydrofuran solution (10 ml), and then cooled to 0 ° C, and benzamidine chloride was slowly added dropwise. (0.29ml-293-200526665 (289)). After the reaction mixture was stirred at room temperature for 1 hour, a 2 mol / l sodium hydroxide aqueous solution (2.0 ml) was added dropwise, and the reaction was terminated by stirring for 18 hours. 1 mol / 1 of hydrochloric acid (4.0 ml) was added to neutralize, and common salt was added until the solution was saturated, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate only) to obtain the title compound (0.5 1 g, yield, quantitative). The ESI / MS data of this compound are shown below. ESI / MS m / e: 514.4 (M + + H, C24H24ClN5004S) Example 23 N- [5- (2-aminoethyl) -6- (3-chloro (2-thienyl))-oxy (3-Hydropyrrole [3,2-d] pyrimidin-7-yl)] Synthesis of benzamidine hydrochloride (compound number: 2 0 8)%

Add 4mo 1/1 hydrochloric acid / 1,4-dioxane solution (6.6ml) to (Third-butoxy) -N- {2- [6- (3-chloro (2-thienyl))- A solution of 4-oxy-7- (phenylcarbonylamino) (3-hydropyrrole [3,2-d] pyrimidin-5-yl)] ethyl} amidamine (0.5) g in methanol (3.3ml) ), And stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure to obtain a purified product of the title compound (0.47 g). The ESI / MS data of this compound are shown below. -294- 200526665 (290) ESI / MS m / e: 414.3 (M + + H, C) 9Hi5ClN502 · HC1) Example 24 N- {2- [6- (3-chloro (2-thienyl)) ·· 4-oxy_7- (phenylcarbonylamino) (3-hydropyrrole [3 '2-d] pyrimidin-5-yl)] ethyl} (4-fluorophenyl) fluorenamine (compound Number: 346)

Add 4-fluorobenzyl chloride (23 · 6 μΐ) and triethylamine (55 M1) to the heart containing [5- (aminoethyl) -6- (3-chloro (2-thienyl)) _ 4-oxygen (3-Hydropyrrole [3,2-d] pyrimidin-7-yl)] benzamide (45 mg) in a solution of dimethylacetamide (1. 〇πι 1), and stirred at room temperature 1 hour. A 2 m ο 1/1 aqueous solution of sodium hydroxide (1.0 m 1) was added dropwise, followed by stirring for 1 hour to terminate the reaction. Then, 1 mol / 1 of hydrochloric acid (2.0 ml) was added to neutralize, common salt was added until the solution was saturated, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off under reduced pressure, and the residue was purified by fractional HPLC to obtain the title compound (25.5 mg, yield, quantitative). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. Η PLC holding time = 8 · 2 (minutes)】 H-NMR (400MHz, DM SO-d6) δ (ppm): 3.50-3.70 (m. 2H), 4.35 (brs, 1H), 4.68 (brs, 1H) , 7.12 (d, J = 5.4, 1H), 7.22 (t, -295- 200526665 (291) J = 8.8; 2H) 5 7.44 (t, J = 7.3? 2H), 7.4 7-7.5 6 (m, 1H ), 7.69- 7.78 (m, 3H), 7.84 (d, J = 7.6, 2H), 7.89 (s, 1H), 8.47 (t, J = 5.4, 1H), 9.72 (s, 1H), 12.22 (brs , 1H). ESI / MS m / e: 5 3 6.4 (M 10 + H, C 2 6 H) 9 C 1 FN 5 O 3 S) Example 25 N- {6- (3-chloro (2-thienyl))- 4-oxy- 5- [2- (quinazolin-4-ylamino) ethyl] (3-hydropyrrolo [3,2-d] pyrimidine · 7-yl)} benzidine (Compound Number: 82)

Dissolving N- [5- (2-aminoethyl) -6- (3-chloro (2-thienyl)) oxy (3-hydropyrrole [3'2-d] pyrimidin-7-yl)]- Benzoxamine (45 mg) and 4-chloroD-quinazoline (16.5 mg) were added to dimethylacetamide (2.9 ml), and triethylamine (27.7 μΐ) was added and stirred at 70 ° C for 3 hours. Triethylamine (1 3.9 μ 1) was further added, and stirred at 70 t: for 5 hours. After the reaction solution was cooled to room temperature, it was directly purified by fractional HP LC to obtain the title compound (4 4.3 mg, yield 82%). The Η P L C retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 6.4 (minutes) 1H-NMR (400MHz, DMSO-d6) (5 (ppm): 3.9 5 -4.05 (m? 2H) 5 • 296- 200526665 (292) 4.52 (brs, 1H), 5.00 ( brs, 1H), 7.05 (d, J = 5.4, 1H), 7.43 (t, J = 7.6, 2H), 7.52 (t, J = 7.3, 1H), 7.65 (d, J = 5.4, 1H), 7.70 -7.85 (m, 5H)? 8.02 (t? J-7.8, 1 H), 8.2 3 (d, J = 8 · 5, 1 H), 8.61 (s, 1H), 9.66 (s, 1H), 10.17 (m, 1H), 12.10 (brs, 1H). ESI / MS m / e: 542.4 (M + + H, C27H2OC1N702 S) Example 26 (third butoxy) -N- [2- [6 · (3-chloro (2-thienyl))-4-oxy-7-ethylene (3-hydropyrrole [3,2-d] pyrimidin-5-yl)] ethyl] fluorenamine (compound number · 966)

In a nitrogen-substituted flask, a 0.5 M zinc chloride tetrahydrofuran solution was placed, and stirred and added]. 0 M vinylmagnesium bromide in tetrahydrofuran solution 1.0 mg, and stirred for 30 minutes. The resulting suspension was used in the following reaction. In a round-bottomed flask, (third butoxy) -N- {2- [6- (3-chloro (2 · thienyl))-4-oxy-7-iodine (3-hydropyrrolidine [ 3,2-d] pyrimidin-5-yl)] ethyl} amidamine (26 mg) and four triphenylphosphine palladium (0) (12 mg). After replacing with nitrogen, anhydrous tetrahydrofuran (2 ml) was added. The above suspension (600 μΐ) was added, and the mixture was stirred at 5 ° C for 8 hours. Saturated saline was added and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting refined product -297- 200526665 ( 293) Using silica gel chromatography (eluent: hexane / ethyl acetate = 5/1 0/1) to obtain the title compound (5.5 mg, yield, 26%). HPLC retention time and ESI / MS data. HPLC retention time = 9.6 (minutes) ESI / MS m / e: 421.2 (M + + H, Ci9H21C1N403 S) Example 27 (third butoxy) -N- {2- [6- (3-Chloro (2-thienyl))-7- (3-hydroxy-1-propyn-1-yl) -4-oxy (3-hydropyrrole [3,2-d] pyrimidine -7-yl)] ethyl} fluorenamine (compound number: 971)

In a round-bottomed flask, 26 mg of (third butoxy) -N- {2- [6- (3-chlorothienyl))-4-oxy-7-iodine (h-pyrrolidine [3, 2_ d] pyrimidin-5-yl)] ethyl} amidamine, 12 mg of four triphenylphosphine palladium, 3.8 mg of cuprous iodide and 15 μΐ of propynyl alcohol 'were substituted with nitrogen, and then added 1 ml Anhydrous tetrahydrofuran and 209 μΐ of diethylamine. After stirring at 50 ° C for 5 hours, saturated brine was added and the mixture was extracted with ethyl acetate. After the organic layer was concentrated, the column was subjected to silica gel column chromatography (developing solvent 'methanol 10 ml, followed by ethyl acetate: methanol = 2:18 ml), and then the ethyl acetate / methanol elution fraction was concentrated to provide fractional distillation HPLC. The title compound was obtained. The following shows -298- 200526665 (294) HPLC retention time and ESI / MS data of this compound. HPLC retention time = 9.0 (minutes) ESI / MS m / e: 44 8.9 (M + + H, C20H2iC1N4〇4S) Example 28 N- {2- [7 -Benzamidine [d] furan-2-yl -6- (3-chloro (2-thienyl). 4-oxy (3-hydropyrrole [3,2-d] pyrimidine · 5-yl)) ethyl] (third butoxy ) Synthesis of sulfonamide (compound number: 1000)

In a round bottom flask, 26 mg of (third butoxy) -N- {2- [6- (3- (2-thienyl))-4-oxy-7-iodine (3 · hydropyrrole) [3,2-d] pyrimidin-5-yl)] ethyl} fluorenamine, 2.2 mg of palladium acetate, triphenylphosphine, 26 mg of sodium carbonate, and 16.2 mg of 2-phenylhydrazone-d-furanylboronic acid. After replacing it with nitrogen ', dimethylformamide: water = 2: 1 solution 1 ml 1 was added, and stirred at 80 ° T for 24 hours. Saturated saline was added and extracted with ethyl acetate. After the organic layer was concentrated, it was subjected to silica gel column chromatography (developing solvent, 10 ml of toluene, followed by ethyl acetate: methanol = 2:18 ml), and the ethyl acetate / methanol fraction was concentrated. Fractional HPLC was provided to give the title compound. The HPLC retention time and ESI / MS data of this compound are shown below. HPLC retention time =] 1.6 (minutes) -299- 200526665 (295) ESI / MS m / e: 5 11.3 (M + H, C25H23ClN4〇4S) Example 2 9 N- {2- [6- (3 -Chloro-¾phen-2 -yl) -7 -iodo-4 -oxy-3 -hydrogenated D ratio slightly higher than [3 '2-d] D-D-5-yl] -ethyl second butyl- Synthesis of Otomo Moon Lady (Compound No. 625)

Add tert-butylacetamidine chloride (95mg) to 5- (2-aminoethyl) -6- (3-chloro-thiophene-2-yl) -7-tele-3-gasification In 3 ′ 2- (1) tridin-4-one hydrochloride (173mg) in N, N-dimethylformamidine (5.0ml), after stirring at room temperature, triethylamine (1 (0ml) and then stirred at room temperature for 2 hours. Water (1.0ml) was added to the reaction solution and stirred at room temperature overnight. The resulting solution was extracted with ethyl acetate (10ml twice). The organic layer was saturated with brine. After washing, the solvent was distilled off under reduced pressure. The obtained refined product was purified by silica gel column chromatography (ethyl acetate only) to obtain the title compound (160 mg, yield 88%). The following is shown below NMR data and ESI / MS data of the compound. 1H-NMR (400MHz ^ DMSO-d6) δ (ppm): 0.84 (s, 9H), 1.81 (d, J = 3.67, 2H), 3.25 -3.34 (m, 2H ), 4.05-4 · 12 (π, 1H), 4.44-4.50 (m, 1H), 7.28 (d, J = 5.36, 1H), 7.69 (t, J = 5.86, 1H); 7.92 ( d? J = 3.6 7 5 ih) 5 8.0 (d5 J = 5.36? 1H)? l2.25 (brs, -300- 200526665 (296) 1 Η). ESI / MS m / e: 519.1 (Μ + + Η , C18H20C1IN4〇2S) implementation Example 3 0 N-{2-[7-(1 H-Dttazole-4 -yl) -6-(3 -Ga-fluoren-2-yl) -4-oxy-3-hydropyrrole [3, 2-d] pyrimidin-5-yl] -Synthesis of triethylacetamide (compound number: 629)

In a vial with a screw cap, put N- {2- [6- (3-chloro · fluoren-2-yl) -4-oxy-7-iodo-3-3-hydropyrrole [3 ' 2-d] Chrysentidine-5-yl] diphenyltributylbutylacetamide (26 mg), palladium acetate (2.2 mg) 'mono-tetramethylphosphine (5.2 mg), sodium carbonate (26mg) and (4 '4' 5'yl, 3,2] -dioxyborane-2-yl) -1H-pyrazole (19.4mg) 'After replacing with nitrogen, add dimethylformamide : Water ^ 2: 1 solution (lml) was stirred at 80 ° C for 12 hours. The resulting solution was added with saturated brine and extracted with ethyl acetate. After concentrating the organic layer, it was purified by fractional HP LC to obtain the title compound. (5.2 post, yield 23%). The HpLc retention time, NMR data, and ESI / MS data of this compound are shown below. Η PLC retention time =] 0.9 (minutes) nm nmrhoomhz, DMS〇-d6) 5 ( ppm): 〇85 (s, called) -301. 5 200526665 (297) 1.84 (d, J = 1.685 2H), 3.30-3.38 (m, 2H), 4.04-4.11 (m, 1H), 4.3 5-4.4 0 (m, 1 H), 7 · 3 4 (d, J = 5. 3 8, 1 H), 7 · 4 4 (brs, 2 H), 7.76 (t, J = 5.60, 1H), 7.93 ( s5 1H), 8.05 (d, J = 5.38, 1 H), 12.17 (brs? 1 H) c ESI / MS m / e: 45 9.3 (M + + H, C2iH23ClN602S) Example 31 5- (2-aminoethyl) -6- (3-chloro-thiophene- Synthesis of 2-yl) -7-pyridin-3-yl-3-hydropyrrolo [3,2-d] pyrimidin-4-one (Compound No. 209) 2 Hydrochloride

Dissolving (Third Butoxy) -N- {2- [6- (3-chloro-thien-2-yl) -7-pyridine · 3 · yl-3 -yl-4 -oxy-3 -hydropyrrole骈 [3,2-d] pyrimidin-5 · yl; | -ethyl} amidamine (1.68g) in methanol (] .00m]), 4mol / l hydrochloric acid / 1,4-dioxane was added The alkane solution (2.0 ml) was stirred at 60 ° C for 12 hours. After the reaction mixture was cooled to room temperature, the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure to obtain the title compound (1.64 g, yield, quantitative). The ESI / MS data of this compound are shown below. ESI / MS m / e: 371.9 (M + + H, Ci7H] 4C1N50S 2HC1) Example 32]-{2- [6- (3-chloro-thien-2-yl) -4-oxy-7 -Pyridin-3-yl-3-hydropyrrole [3,2-d] pyrimidin-5-yl] -ethyl 3- 3-phenyl- -302- 200526665 (298) Synthesis of urea (compound number: 793)

Add phenyl isocyanate (20mg) to 5- (2-aminoethyl) -6- (3-chloro-thiophene-2-yl) -7-pyridine-3-yl-3-pyrrole [3 '2-d] N, N-dimethylformamidine (] · 0χη1) in uridine-4-one 2 hydrochloride (25 mg), and after temporary stirring at room temperature, triethylamine ( 2π1) Stir for 2 hours at room temperature. Saturated saline was added to the obtained solution, and the mixture was extracted with ethyl acetate. The residue was distilled under reduced pressure, and the residue was purified by fractional distillation HP LC to obtain the title compound (8 mg, yield, 29%). The HP LC retention time and ESI / MS data of this compound are shown below. HPLC retention time = 6.6 (minutes) ESI / MS m / e: 491.04 (M + + H ^ C 2 4 Η i 9 C IN 6 〇 2 S) Example 33 4-fluoro-hexahydropyridine-l -{2- [6- (3-chloro-thien-2-yl) -4-oxy-7-pyridin-3-yl-3-hydropyrrole [3,2-d] pyrimidin-5-yl; Synthesis of I-ethylbutanamine (compound number: 550) -303- 200526665 (299)

Add triethylamine (0.078ml) and triphosgene (I7mg) to 5- (2-aminoethyl) -6- (3-chloro-thien-2-yl) -7-pyridin-3-yl-3- Pyrrolidine hydrochloride [3,2-d] pyrimidin-4-one 2 hydrochloride (25 mg) in a solution of chloroform (1.0 m 1) 'was temporarily stirred at room temperature, then 4-fluorohexahydro was added Pyridine (12 mg) was stirred at room temperature for 3 hours. Saturated saline water was added to the obtained solution, and the mixture was extracted with ethyl acetate, followed by distillation under reduced pressure. The residue was purified by fractional distillation of HP LC to obtain the title compound (1.2 mg, yield 5%). The HPLC retention time and ESI / MS data of this compound are shown below. HPLC retention time = 6.9 (minutes) ESI / MS m / e: 501.41 (M + + H »C 2 3 H 2 2 C 1 FN 6 〇 2 S) Example 3 4 5-[2- (bis-cyclopropane Methylmethyl-amino) -ethyl] -6- (3-chloro-thien-2-yl) -7-pyridin-3-yl-3-hydropyrrolo [3 '2 4] pyrimidin-4-one (Compound Number: 1057) Synthesis

-30420052005665 (300)

Add cyclopropanal (5mg), triacetoxy sodium borohydride (24mg) and acetic acid (0.1ml) to a solution containing 5- (2-aminoethyl) -6 · (3-chloro-thiophene-2-yl ) -7-pyridin-3-yl-3-hydropyrrolo [3,2-d] pyrimidin-4-one 2 hydrochloride (25mg) in N, N-dimethylformamide (1.0ml) Medium 'was stirred at room temperature for 10 hours. The resulting solution was added with saturated saline and extracted with ethyl acetate, and then distilled under reduced pressure. The residue was purified by fractional HPLC to obtain the title compound (10 mg, yield 36%). The HPLC retention time and ESI / MS data of this compound are shown below. HPLC retention time = 5.4 (minutes) ESI / MS m / e: 482.0 (M + + H, C25H25C1FN50S) Example 35 N- {2- [6- (3-chloro-thiophen-2-yl) -4 -oxo Of 7-hexahydropyridin-3-yl-3-hydropyrrolo [3,2-d] pyrimidin-5-yl] -ethyltributylbutylacetamide (compound number · 626) synthesis

Add tert-butylacetamidine chloride (23mg) to 5- (2-aminoethyl) -6- (3 «chloro-heptyl-2-yl) -7-hexachloro DfctUdin-3-yl-3 -Rhenium chloride comparison cake [3,2-d] pyrimidin-4-one 2 hydrochloride (25mg) in N, N-dimethylacetamidamine (1.0ml) solution, temporarily stirred at room temperature Thereafter, triethylamine (0.2 ml) was added and the mixture was stirred at room temperature for 2 hours. Water (-305-200526665 (301) 0.2 ml) was added to the reaction solution, and the mixture was stirred at room temperature overnight. To the obtained solution was added λ &amp; in saturated human salt water, which was extracted with ethyl acetate and then distilled under reduced pressure. Residues &amp; ^.

Purified by HPLC by fractional distillation to obtain the title compound (9 mg, yield 72%). The HPLC retention time and ESI / MS data of this compound are shown. HPLC holding time = 7.6 (minutes) ESI / MS m / e: 470.1 (M + + H, C23H24C1N5 02 S) Example 3 6 1-Methyl-cyclohexylamine-{2- [6- (3 · 气-Fluorenyl) · 4-oxy-7-pyridin-3-yl-3-hydropyrrole [3,2-d] pyrimidin_5_ylbuthylethylpyridine (compound number: 684) synthesis

Add p-methyl-cyclohexanecarboxylic acid (24 mg), p-ethyl 3- (hong dimethylaminopropyl) carbodiimide hydrochloride (43 mg), 'hydroxybenzene triazole (8 mg) and triethylamine (〇 .2ml) containing 5- (2-aminoethyl) -6- (3-chloro-thien-2-yl) -7-pyridin-3-yl-3-hydropyrrole [3,2-d] pyrimidine 4-Keto-2 hydrochloride (25 mg) in N, N-dimethylformamide (UmD solution, stirred at room temperature for 0 hours). After adding saturated brine to the resulting solution and extracting it with ethyl acetate, It was distilled under reduced pressure. The residue was purified by fractional HPLC to obtain the title compound (Π mg 'yield 4]%). The HPLC retention time and ESI / MS data of this compound are shown below. -306- 200526665 (302) is 1 ^ Retention time = 8.2 (minutes) ESI / MS m / e: 496.0 (M + + H, C25H35ClN50 2S) Example 37 Ν- {2 · [6 · (3-chloro (2-thienyl))-4 -Oxy- 7- (3 -pyridinyl) · 3 -pyrrolidine [3 '2 -d] pyrimidin-5 -yl] ethyl) acetic acid

Add 4 mol / l hydrochloric acid / dioxane solution (0.57 ml) to the (third butoxy) -N- {2- [6- (3-chloro (2-thienyl))-4-oxy group -7- (3-pyridyl) (3-hydropyrrolo [3,2-d] pyrimidin-5-yl)]-ethyl} amidamine (356mg) of 1,4 · dioxane (6.0ml) And methanol (1.0 ml), and stirred at 60 ° C for 1 hour. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure to obtain a refined product (370 mg). To the dimethylacetamide solution (2.0ml) of the reaction product (26mg), acetamidine chloride (10mg) and triethylamine (0.2ml) were added, and the mixture was stirred at room temperature for 1 hour. After adding water (0.2 ml) and stirring at room temperature for an additional hour, the residue was purified by fractional HPLC to obtain the title compound (15 mg, yield: 5 7%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. -307- 200526665 (303) HPLC holding time = 5.7 (minutes) 1 H-NMR (400MHz ^ DMS 0-d 6) (5 (pp m): 1. 6 5 (s, 3 Η), 3 · 3 1 _ 3_41 (m, 2H), 4.16 (m5 1H), 4.50 (m, 1H), 7.29 (m, 1H), 7.61 (dd, J = 5.12, J = 8.08, 1H), 7.86 (m, 1H), 7.92 (m, 1H), 8.01 (m, 2H), 8.54 (d, J = 5.12, 1H), 8.64 (s, 1H), 12.38 (brs, 1 H). ESI / MS m / e: 414.4 (M + + H, C19H16C1N5 02 S) Example 3 8 6-(3-chloro (2-thienyl))-7-(3-pyridyl)-5- [2-quinazolin-4-ylamino] Synthesis of Ethyl] -3-hydropyrrole [3,2 4] pyrimidin-4-one (Compound No. 84)

Add 4 mol / l hydrochloric acid / dioxane solution (.75ml) to the (second butoxy) -N- {2- [6- (3-chloro (2-thienyl))-4 · oxy group -7- (3-D than fluorenyl) (3-chlorofluorene ft. Shortcake [3 '2-d] chelated fluorenyl-5-yl)] ethyl} amine (356mg) 1,4- A solution of dioxane (6.0 ml) and methanol (1.0 ml) was stirred at 60 ° C for 1 hour. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure to obtain a refined product (370 mg). Into a solution of the reaction product (32 mg) in dimethylacetamide (-308-200526665 (304) 2.0 ml), forcefully add 4-chloroquinazoline (13 mg) and triethylamine (16 mg), Stir at 70 ° C for 2 hours. After the reaction solution was cooled to room temperature, it was purified by fractional distillation HPLC to obtain the title compound (21 mg, yield 54%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 5.6 (minutes)] H-NMR (400 MHz, DMSO-d6) (5 (ppm): 4.01-4.06 (m9 2H), 4.55 (m, 1H) 5 4.9 6 (m, 1H), 7.08 ( m, 1H), 7.47 (dd, J = 4.88, J = 8.04, 1H), 7.72-7.7 8 (m5 3H), 7.83 (m, 1H), 7.90 (s, 1H), 8.02 (t, J = 7.68 , 1H), 8.23 (d5 J = 8.52, 1H), 8.46 (d, J = 5.12, 1H), 8.52 (s, 1H), 8.67 (s5 1H), 10.18 (m, 1H), 12.30 (brs, 1 H). ESI / MS m / e: 500.4 (M + + H, C25H18C1N70S) Example 3 9 3-(4-oxy-7- (3-pyridyl) -3-hydropyrrole [3, 2- d] Synthesis of pyrimidin-5-yl) ethyl propionate (compound number: 35)

Formamidine acetate (7.18 4g) was added to isopropanol containing ethyl 3- [3 · amino-2- (methoxycarbonyl)-[(3-pyridyl) pyrrolidyl] propionate (4.380g) (80 ml) of the solution, stirred at 90 ° C for 10 hours. After cooling the reaction solution to -309- 200526665 (305), the resulting solid was filtered and the filtrate was distilled off under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. After filtering sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / ethanol = 7/1) to obtain the title compound (0.747 g, yield 17%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 5.6 (minutes)] Η-NMR (4 0 0 Μ H z, DMS 0-d 6) (5 (ppm): 1 · 1 1 (t, J = 7 · 0 8, 3H)? 2.95 (t? J = 6.96? 2H)? 4.03 (dd, J = 6.96, J = 14.28? 2H), 4.63 (t, J = 6.84, 2H) 5 7 · 8 1 (dd, J = 5. 1 2, J = 8 · 0 4, 1 H), 7 · 9 9 (s, 1H), 8.22 (s, 1H), 8, 60 (d5 J = 5.12, 1H), 8.81 (d, J = 8.04, 1H) , 9.38 (s, 1H) 5 12.29 (s, 1H). ESI / MS m / e: 313.2 (M + + H, C16H] 6N403) Example 40 3-(4-oxy-7- (3-pyridine ) (3-Hydropyrrolo [3,2-d] pyrimidine · 5-yl))-N-phenylpropanamine (Compound No. 30)

Add water (0.40ml) and 5M aqueous sodium hydroxide solution (0.18ml) to -310- 200526665 (306) containing 3- (4-oxy-7- (3-pyridyl) -3-hydropyrrole [3 ' In a solution of ethyl 2-d] pyrimidin-5-yl) propanoate (91 mg) in 1,4-dioxane (3.0 ml), the mixture was stirred at room temperature for 2 hours. Neutralization with acetic acid was carried out, and the resulting solid was filtered and washed with water and ethyl acetate to obtain a purified product (78 mg). To a mixed solution of dichloromethane (1.0 ml) and dimethylacetamide (1.0 ml) containing the reaction product (20 mg), 1-ethyl-3- (3'-dimethylaminopropyl) was added Carbodiimide hydrochloride (41 mg) and pyridine (0.2 ml), and stirred at room temperature for 1 hour. Aniline (20 mg) was added to the reaction solution 'and stirred at 40 ° C overnight. Methanol was added to terminate the reaction, and the solvent was distilled off under reduced pressure. The residue was purified by fractional HPLC to obtain the title compound (19 mg, yield 76%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 6.1 (minutes) 1H-NMR (400MHz, DMSO-d6) δ (ppm): 2.97 (t? J = 6.58? 2H), 4.69 (t5 J = 6.485 2H), 6.99 (t, J = 7.4 6 5 1 H), 7.24 (t, J = 7.92, 2H)? 7.5 1 (d? J = 8.56, 2H), 7.78 (dd, J = 5.50, J = 7.9 4? 1H), 7.99 (s, 1H ), 8.18 (s, 1H), 8.57 (d, J = 5.40, 1H), 8.78 (d, J = 8.04, 1H), 9.36 (s, 1H), 9.96 (s, 1H), 1 2.30 (brs, 1 H) ° ESI / MS m / e: 360.2 (M + + H, C20H17N50 2) Example 41 6-chloro-5-benzyl-7- (3 · pyridyl) -3-hydropyrrole [ Synthesis of 3,2-d] pyrimidin-4-one (Compound No. 1180) 200526665

Add N-chlorosuccinimide (57mg) to the second containing 5-benzyl · 7 · (3-pyridyl) -3-hydropyrrolo [3,2-d] pyrimidin-4-one (65mg) In a solution of methylformamide (2.0ml), stir at room temperature for 2 hours °, add N-chlorosuccinimide (57mg), stir at room temperature for 2 hours °, add water (0.2ml) to stop the reaction, Purification by fractional HP LC gave the title compound (33 mg, yield 46%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. Η PLC holding time = 8 · 0 (minutes)] Η-ΝΜΙΙ (400ΜΗζ, DMSO-d6) ά (ppm): 5.82 (s? 2H)? 7.22-7.36 (m, 5H), 7.72 (dd, J = 5.12 , J = 8.04, 1H), 8.00 (s, 1H), 8.42 (m? 1H), 8.64 (d? J = 5.12, 1H)? 9.07 (s, 1H)? 12.41 (brs9 1H). ESI / MS m / e: 3 3 7.3 (M + + H, Ci8Hi3C1N4〇) Example 42 7- (3-pyridyl) -4-oxy-6-cyclopropyl-3-hydropyrrole [3, Synthesis of 2-d] pyrimidine (compound number: 1178)

-312- 200526665 (308) A 100 ml eggplant-shaped flask was charged with 3-amino-4- (3-pyridyl) -5 · cyclopropylpyrrole-2-carboxylic acid ethyl ester (118 mg), isopropyl alcohol (40 ml ) And formazan acetate (1.35g), and heated and stirred at 95 ° C for 13 hours. After the reaction was completed, the solvent was concentrated under reduced pressure, and water (20 ml) and ethyl acetate (20 ml) were added to separate the concentrated residue, and the aqueous layer was re-extracted with ethyl acetate (20 ml). After the organic layer was washed twice with water (20 ml), the organic layer was dehydrated with magnesium sulfate, dried, filtered, and concentrated to obtain a crude product (91 mg). This crude product was washed three times with methanol (1 ml) to obtain the title compound (49 mg, yield 45%). The HPLC retention time and ESI / MS data of this compound are shown below. HPLC retention time = 4.1 (minutes) ESI / MS m / e: 2 5 3.1 (M + + H, C] 4H12N40) Example 43 (third butoxy) -N- {2- [6- (3- Chloro (2-thienyl))-4-oxy-7- (trifluoromethyl) (3-hydropyrrole [3,2-d] pyrimidin-5-yl)] ethyl} fluorenamine (compound number ·· 947)

Under nitrogen, the suspension of dry dimethylformamide (10ml) containing cadmium (2.24g) was stirred under ice-cooling, and dibromodifluoromethane-313-200526665 (309) (1.5ml) was added, Stir at room temperature for 3 hours. Dry hexamethylphosphamide (10 ml) was added, and cuprous bromide (1.16 g) was added to the ice-cold mixture, followed by stirring at room temperature for 1 hour to obtain a suspension of a trifluoromethyl copper compound. Add the suspension (10 ml) of the above trifluoromethyl copper compound to the (third butoxy) -N- {2- [6- (3-chloro (2-thienyl))-4-oxo Of dimethyl-7- (trifluoromethyl) (3-hydropyrrolo [3,2-d] pyrimidin-5-yl)] ethyl} fluorenamine (U5mg) in dry dimethylformamide (3ml) The mixture was stirred at 65 t for 6 hours. Aqueous ammonium chloride solution was added and extracted with ethyl acetate. The organic layer was washed with brine, dehydrated with sodium sulfate, filtered and concentrated, and then purified by silica gel chromatography to obtain the title compound (35 mg, yield 34%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 12.1 (minutes) 1H-NMR (270 MHz, CDC13) δ (ppm): 1.32 (s? 9H)? 3.35- 3.60 (m, 2H), 4.00-4.3 0 (m, 1H) , 4.40-4.70 (π, 1H), 7.11 (d, J = 5.1Hz, 1H), 7.61 (d, J = 5.4Hz, 1H), 7.95-8.10 (m, 1H). ESI / MS m / e: 463.2 (M + + H, C18H18C1F3N4〇3s) Example 4 4 6 · Phenyl-7 · (3 · Pyridyl) -3 -hydropyrrolo [3 '2-d] pyrimidinone (Compound Number: 205) Synthesis

• 314- 200526665 (310) will contain 6-chloro-7- (3-pyridyl) -3-hydropyrrolo [3,2-d] pyrimidin-4-one (40mg), phenylboronic acid (&lt; 9mg ) And potassium acetate (78mg) in N, N-dimethylformamide / water (2 ·· 1) solution (1.0ml) and degassed, then add a small amount of [1,1'-bis (diphenyl Phosphino) ferrocene] palladium (II) chloride, a complex of dichloromethane (1: 1). The reaction mixture was heated in a microwave at 140 ° C for 5 minutes. The solvent was distilled off under reduced pressure, and the residue was separated into an ethyl acetate layer and an aqueous layer. The organic layer was washed with a saturated sodium bicarbonate aqueous solution and a saturated sodium chloride solution, dehydrated with sodium sulfate, and after filtering off sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (0 to 5% methanol / ethyl acetate), and then purified by fractional HP LC to obtain the title compound (6.3 mg, yield 10Λ). The HPLC holding time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 4.0 (minutes)] Ν-ΝΜΙΙ (400 ΜΗζ, CD 3 Ο D) (5 (ppm): 7 · 5 0 (m, 5 Η), 7 · 8 6 (dd, J = 5.7, J = 8.2, 1H) 5 7.9 8 (s, 1H), 8.44 (dt, J = 1.6, J = 8.2, 1H), 8.62 (d, J = 5.7, 1H), 8.94 (s, 1H). ESI / MS m / e: 2 8 9.1 (M + + H, C17H] 2N40) Example 45 Ethyl 4- (4-oxy-3-hydropyrrolo [3 '2-d] pyrimidin-5-yl) butanoate ( Synthesis of compound number: 2501)

-315- 0 200526665 (311) Dissolve 4- [3-amino-2- (ethoxycarbonyl) pyrrolyl] butyric acid ethyl ester hydrochloride (20.1g) in dichloromethane (400ml), add saturated Aqueous sodium bicarbonate solution (400 m 1). The reaction mixture was stirred for 30 minutes and separated into two layers. The aqueous layer was extracted with dichloromethane, and the combined organic layer was washed with saturated brine, and then dehydrated with magnesium sulfate and concentrated to remove the magnesium sulfate. The solvent was removed under reduced pressure to obtain a 4- [3-amino group. -2- (ethoxycarbonyl) pyrrolyl] ethyl butyrate (18.0 g). This compound was dissolved in isopropanol (400 nil), and formamidine acetate (9.7 8 g) was added. The mixture was heated at reflux for 150 minutes. The solvent was distilled off under reduced pressure, and the residue was separated into a dichloromethane layer and an aqueous layer. The aqueous layer was extracted with dichloromethane, and the combined organic layer was washed with a 10% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate solution, and a saturated saline solution. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (13.0 g, yield 78%.). The NMR data and ESI / MS data of this compound are shown below. ] H-NMR (400 MHz, DMSO-d6) &lt; 5 (ppm): 1 · 1 4 (t, J = 7 · 1, 3 Η), 2.01 (pent, J = 7.0; 2H), 2.21 (t, J = 7.5, 2H), 3.99 (q5 J = 7.1, 2H)? 4.38 (t5 J = 6.7? 2H), 6.33 (d? J = 2.9? 1 H), 7, 4 1 (d, J = 2 · 9 5 1H), 7.76 (s, 1H) 5 1 1.86 (brs, 1H). ESI / MS m / e: 250.1 (M + + H, C12H15N3 03) Example 46 4- (7-iodo-4-oxy-3-hydropyrrole [3,2-d] pyrimidin-5-yl) Synthesis of ethyl butyrate (compound number: 2502) -316- 200526665 (312)

Add N-Iodide succinimide (12.8g) to ethyl 4- (4- "3-hydropyrrolo [3,2-d] pyrimidin-5-yl) butanoate (12.9g dichloromethane (3 5 (0ml) solution, stirred at room temperature overnight. After washing the filtrate with diethyl ether, it was dried under reduced pressure to obtain the title compound (1.18g, 61% yield). The filtrate was concentrated under reduced pressure, and acetic acid was added. Ethyl residue was stirred vigorously. The solids that occurred were collected by filtration, washed with ethyl acetate and ether, and dried under reduced pressure to obtain the title compound (6.63 g, 34%). The NMR data of this compound are shown below. ESI / MS data. H-NMRMOOMHz, DMSO-d6) (5 (ppm): 1. 1.3 (t, J = 7 · 1, 2.02 (pent, J = 7.0? 2H)? 2.2 2 (15 J = 7.4 5 2 H), 3.96 (q? J = 2H) 5 4.3 9 (t? J = 6.7, 2H), 7.63 (s, 1H), 7.85 (s, 12.06 (brs, 1H). ESI / MS m / e : 3 7 6.0 (M + + H, C] 2H] 4IN3 03) Example 47 4- (4-oxy-7- (3-pyridyl) -3-hydropyridine [3 '2-d] pyrimidine- 5-yl) ethyl butyrate (compound number: 2512) into ft-based-) solids (in the residual diethyl yield 3H)? = 7.1, 1H), slightly mixed -317- 200526665 (313)

• According to the same method as in Example 28 using 4- (7-iodo-4-oxy-3-hydropyrrole [3,2-d] pyrimidin-5-yl) butyric acid ethyl ester and 3-pyridylboronic acid

To give the title compound. The NMR data and ESI / MS data of this compound are shown below. IH-NMR (400MHz, DMSO-d6) 5 (ppm): 1.1.11 (t, J = 7.1, 3H), 2.09 (pent, J = 7.0, 2H), 2.29 (t? J = 7.4, 2H), 3.96 (q, J = 7.1, 2H), 4.45 (t, J = 6.7, 2H) 5 7.41 (m, 1H), 7.93 (s, 1H), 8.06 (s, 1 H), 8.40 (m, 2H) , 9.2 1 (m, 1 H), 1 2 · 1 0 (s, br, 1 H). ESI / MS m / e: 3 2 7.0 (M + + H, C17Hi8N403)

Example 48 of 4- (4-oxy-7 · (3-pyridyl) -3-hydropyrrole [3,2-d] pyrimidin-5-yl) butanoic acid (compound number: 2 5 0 3) synthesis

Add 1M lithium hydroxide aqueous solution (6.3ml) to 4- (4-oxo-318-200526665 (314) yl-7- (3-pyridyl) -3-hydropyrrole [3,2-d] pyrimidine In a solution of ethyl-5-yl ethyl butyrate (0.78 g) in ethanol (24 ml) and water (3 ml), it was stirred overnight at room temperature. The solvent was distilled off under reduced pressure, and water (5 ml) was added to the residue. 1M hydrochloric acid was added to adjust the solution to pH 4, and the resulting solid was collected by filtration. Drying under reduced pressure gave the title compound (0.75 g, yield, quantitative). The NMR data and ESI / MS data of this compound are shown below. / H-NMRyOOMHz, DMSO-d6) δ (ppm): 2 · 0 7 (pent, J = 7 · 0, 2H), 2.23 (t, J = 7.3, 2H), 4.46 (t5 J = 6.7, 2H) , 7.77 (dd, J = 4.3? J = 8.2? 1 H) 5 7.9 8 (s, 1H), 8.24 (s5 1H), 8 · 5 8 (d, J = 4 · 3, 1H)? 8.79 (d ? J = 8.2? 1H)? 9.39 (s5 1H)? 12.12 (brs? 1H)? 12.24 (brs, 1H). ESI / MS m / e: 299.1 (M + + H ^ C15H14N4O3) Example 49 4- (4-oxy-7- (3-pyridyl) (3-hydropyrrolo [3 '2-d] pyrimidine- Synthesis of 5-yl))-N-benzyl butyric acid ammonium (Compound No. 2292)

Add diisopropylethylamine (91 μΐ) and benzylamine (29 μΐ) to a solution containing 4 · (4-oxy-7- (3-pyridyl) -3-hydropyrrole [3,2-d] Pyrimidine-319- 200526665 (315) pyridin-5-yl) butanoic acid (40 mg) in a solution of 2N, N-dimethylformamide (4mi). Then add 0- (7-azabenzimidazolyl) -N, N, N ,, N'-tetramethyluronic acid /, and fluorophosphate ^ "⑺㈠, and stir at room temperature overnight. The solvent was distilled off under reduced pressure, and the water was heated to the residue. The insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure to obtain the title compound (16 mg, yield 22%). The hplc retention time, NMR data and ESI / MS data. HPLC retention time = 5.1 (minutes) iH-NMRMOOMHz, DMSO-d6) (5 (ppm): 2. 1 2 (m5 4H)? 4.23 (d, J = 6.0, 2H), 4.46 (t , J = 6.3, 2H), 7.22 (m, 3H), 7.30 (m, 2H) 5 7.73 (dd, J = 5.0, J = 8.2, 1H), 7.98 (s, 1H)? 8.19 (s, 1H) , 8.33 (t, J = 6.0, 1H), 8.56 (d, J = 5.0, 1H), 8.74 (d, J = 8.2 to 1H), 9.37 (brs, 1H), 12.22 (brs, 1 H). ESI / MS m / e: 3 8 8 · 1 (M + + Η, C 2 2 Η 2! N 5 Ο 2)

Example 5 0 4 · (6 -Ga-4 · oxy-7-(3 -Cyridinyl)-^ -Gasification ratio [3,2-d] pyrimidin-5-yl) butyl Synthesis of Ethyl Ester (Compound No. 2504)

〇 -320- 200526665 (316) 4- (4-oxy-7- (3-pyridyl) -3-hydropyrrole [3,2-d] pyrimidin-5-yl) butyric acid ethyl ester (1.72 g)-After heating to dissolve in dichloromethane (63 ml), cool to 0 ° C. After adding 2 mol / l of a sulfosulfonyl chloride / dichloromethane solution (7.9 ml) to the above solution, the mixture was stirred at room temperature for 3 hours. After the solvent was distilled off under reduced pressure, dichloromethane and a saturated aqueous sodium hydrogen carbonate solution were added and stirred vigorously. It was separated into two layers, and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with saturated brine, and dried over sodium sulfate. After the sodium sulfate was filtered off, the solvent was distilled off under reduced pressure to obtain the title compound (1.8 9 g, yield, quantitative). The NMR data and ESI / MS data of this compound are shown below. ] H-NMR (400MHz, DMSO-d6) 5 (ppm): J = 7.1, 3H), 2.06 (pent, J = 7.0, 2H)? 2.37 (t? J = 7.2? 2H), 2.37 (t, J = 7.2? 2H), 3.94 (q, J = 7.1, 2H), 4.58 (t, J = 6.7, 2H), 7.51 (dd, J = 4.7, J = 7.9, 1H), 7.93 (d, J = 3.0 , 1H), 8.13 (dt, J = 1.9, J = 7.9, 1H), 8.54 (d, J = 4.7, 1H), 8.94 (s, 1H), 12.28 (brs5 1 H) 〇ESI / MS m / e : 361.1 (M + + H? C 17 Η i 7 C IN 4 〇3) Example 51 4- (6-chloro-4 · oxy-7- (3-pyridyl) -3-hydropyrrole [3 Synthesis of 2,2-d] pyrimidin-5-yl) -butyric acid (Compound No. 2505)-321 · 200526665 (317)

Add 1M lithium hydroxide aqueous solution (8.6ml) to 4- (6-chloro-4-oxy-7- (3-pyridyl) -3-hydropyrrole [3,2-d] pyrimidine-5- In a solution of ethyl) butyrate (1.24 g) in ethanol (35 ml), it was stirred at room temperature overnight. 1M hydrochloric acid (8.6 ml) was added, and the solvent was distilled off under reduced pressure to obtain a mixture of the title compound and lithium chloride (1.73 g). The NMR data and ESI / MS data of this compound are shown below. 1H-NMR (400MHz ^ DMSO-d6) δ (ppm): 2.02 (m, 2H), 2.29 (t, J = 7.4, 2H), 4.57 (t, J = 6.9, 2H), 7.58 (ddd, J = 0.85 J = 4.9, J = 8.0, 1H), 7.94 (s, 1H), 8.23 (ddd, J = 1.5, J = 2.3, J = 8.0, 1H) 5 8.57 (dd, J = 1.5, J = 4.9, 1H), 8.98 (dd, J = 0.8, J = 2.3, 1H) 5 12.16 (brs, 1H), 12.39 (brs, 1H). ESI / MS m / e: 3 3 3.1 (M + + H, C15H] 3ClN4〇3 LiCl) Example 52 4- (6-chloro-4-oxy-7- (3-pyridyl) (3-hydrogen [3 '2-d] Branyl-5-yl)) ·· Synthesis of N- (cyclohexylmethyl) butyric acid amine (compound number: 2264) -322- 200526665 (318)

Cyclohexanemethylamine (27mg) and diisopropylethylamine (84 μΐ) were added to the solution containing 4- (6-chlorooxy-7- (3-b-pictyl) -chloride). [3, 2-d] pyrimidin-5-yl) -butyric acid (40 mg) in N, N-dimethylformamide (1 ml). Then add 0- (7-azabenzylidenetriazol-1-yl) -N, 1 ^, ^^, and T-tetramethyluronic acid hexafluorophosphate (5511 ^), and stir at room temperature 2 hours. The reaction mixture was separated into an ethyl acetate layer and an aqueous layer. The organic layer was washed with lmo 1/1 aqueous citric acid solution, saturated sodium bicarbonate aqueous solution and saturated saline solution, dehydrated with sodium sulfate, filtered off sodium sulfate, and distilled to remove the solvent under reduced pressure. The residue was purified by silica gel column chromatography (5% methanol / ethyl acetate) to obtain the title compound (35 mg, yield 68%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 7.2 (minutes) 1H-NMR (400 MHz ^ CD 3 OD) 5 (ppm): 0.90 (m5 2H)? 1.21 (m? 3H), 1.42 (m, 1H), 1.69 (m , 5H), 2.16 (m5 2H), 2.29 (t, J = 7.4, 2H), 2.95 (d, J = 7.0, 2H) 5 4 6 6 (t, J = 6 9, 2H), 7.53 (ddd, J = 0.9? J = 5.0? J = 8.0? 1H), 7.89 (s? 1H), 8.22 (ddd, J = 1.6, J = 2.25 J = 8.0, 1H)? 8.49 (dd? J = 1.6, J = 5.0? 1H)? 8.93 (dd? J = 0.9? J = 2.25 1H). -323- 200526665 (319) ESI / MS m / e: 428.2 (M + + H, C32H26ClN50 2) Example 53 4- [6 · (3,4-dimethoxyphenyl) · 4-oxy -7- (3-pyridyl) (3-hydropyrrolo [3,2-d] pyrimidin-5-yl)]-N- (cyclohexylmethyl) butanamide (compound number: 2269)

Will contain 4- (6-chloro-4-oxy-7- (3-pyridyl) (3-hydropyrrole [3,2-d] pyrimidin-5-yl))-N- (cyclohexylmethyl ) Ammonium butyrate (50mg), 3,4-dimethoxyphenylboronic acid (64mg) and potassium acetate (

57 mg) of N, N-dimethylformamide / water (2: 1) solution (2 ml) was degassed and replaced with nitrogen. A small amount of a complex compound of [1,1'-bis (diphenylphosphino) ferrocene] palladium (II) chloride methylene chloride (1: 1) was added. The reaction mixture was heated in a microwave oven at 14 ° C for 30 minutes. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (5 ~ 8 ° /. Methanol / ethyl acetate), followed by fractional distillation of HP. Purification by LC to obtain the title compound (12 mg, yield 16%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 8.0 (minutes)] H-NMR (400 MHz, CD3OD) 5 (PPm): 0.85 (m; 2H)? 1.19 (m? 3H), 1.35 (m, 1H)? 1.66 (m? 5H)? 2.01 (m? 2H)? 2.13 (t? -324- 200526665 (320 ) J = 7.4, 2H), 2.88 (d, J = 6.8, 2H), 3.80 (s, 3H), 3.91 (s, 3H), 4.42 (t, J = 7.5, 2H), 7.00 (dd, J = 2.0, J = 8.1, 1H), 7.03 (d, J = 2.0, 1H), 7.13 (d, J = 8.1, 1H), 7.81 (dd, J = 5.6, J = 8.2, 1H), 7.99 (s, 1H), 8.39 (ddd, J = 1.4, J = 2.1, J = 8.2, 1H), 8.52 (d, J = 5.6, 1H), 8 · 90 (d, J = 2 · 1, 1H). ESI / MS m / e: 5 3 0.0 (M + + H, C30H35N5O4) Example 54 4- {7-iodo-4-oxy-3-[(phenylmethoxy) methyl] -3-hydrogen Synthesis of pyrrolidine [3,2-d] pyrimidin-5-yl} butanoate

N, N-dimethylformamidine containing ethyl 4- (7-iodo-4-oxo-3-hydropyrrole [3,2-d] pyrimidin-5-yl) butyrate (4.07 g) To a solution of amine (60 ml), slowly add a small amount of sodium hydride (5 2 1 mg), and stir at room temperature for 30 minutes. After benzyl chloromethyl ether (2.04 g) was added dropwise, it was stirred for another 2 hours. The solvent was distilled off under reduced pressure, and the residue was separated into an ethyl acetate layer and an aqueous layer. The organic layer was washed with water and saturated brine, and dehydrated with sodium sulfate. After sodium sulfate was filtered off, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (15 ~ 30% ethyl acetate / cyclohexane) to obtain the title compound (3.80 g, yield 71%). The NMR data and ESI / MS data of this compound are shown below. -325- 200526665 (321)] H-NMR (400MHz, CDC13) 5 (ppm): 1.25 (t, J = 7 · 1, 3 H), 2.18 (pent, J = 7.0, 2H), 2.32 (t, J = 7.2, 2H), 4.12 (q, J = 7.1, 2H), 4.51 (t, J = 6.9, 2H), 4.65 (s, 2H), 5.50 (s, 2H), 7.22 (s, 1H); 7.29 (m, 1H), 7.33 (m, 4H), 8.03 (s; 1H). ESI / MS m / e: 496.1 (M + + H, C20H22lN304) Example 55 4- {7 · (1-methylpyrazol-4-yl) -4-oxy-3-[[(benzene

Synthesis of Ethylmethoxy) methyl] -3-hydropyrrole [3,2-d] pyrimidin-5-yl] butyrate

Following the same method as in Example 28, 4- (7-iodo-4 · oxy · 3 · [(phenylmethoxy) methyl] -3-hydropyrrole [3,2-d] pyridine) was used. -5-yl} ethyl butyrate and 1-methyl- 4- (4,4,5,5-tetramethyl-1,3,2-dioxyborane · 2-yl) -1 Η- Dttazole gave the title compound. The NMR data and ESI / MS data of this compound are shown below. 1H-NMR (400MHz ^ CD3OD) δ (ppm): 1.16 (t, J = 7 · 1, 3 Η), 2.16 (pent; J = 7.0, 2H), 2.33 (t, J = 7.2 5 2 H), 3.92 (s, 3H), 3.02 (q, J = 7.1, 2H), 4.49 (t, J = 6.7, 2H), 4.68 (s, 2H), 5.56 (s, 2H), 7.22 (m? 1H)? 7.28 (m, 2H), 7.33 (m? 2H) 5 7.5 4 (s? 1H)? 7.86 (d, J = 0.6, 1H), 8.03 (s, 1H) 5 8.1 (s5 1H). -326- 200526665 (322) ESI / MS m / e: 45 0.3 (M + + H, C24H27N5 04) Example 56 4- [6-Chloro-7- (1-methylpyrazol-4-yl) Synthesis of 4-oxy-3-hydropyrrole [3,2-d] pyrimidin-5-yl] -butyric acid (compound number: 25 06)

Contains 4- {6-chloro-7- (1-methylpyrazol-4-yl) -4-oxy-3-[(phenylmethoxy) methyl] -3-hydropyrrole [3, 2-d] Chloridine-5-yl} A solution of ethyl butyrate (220 mg) in concentrated hydrochloric acid (3 ml) was heated at reflux for 1 hour. After the solvent was distilled off under reduced pressure, 2mo 1/1 ammonia in methanol solution (3ml) was added to the residue. The solvent was distilled off under reduced pressure. Imo 1/1 citric acid aqueous solution was added to the residue, and the solid produced was filtered. After washing with water and diethyl ether, the residue was dried under reduced pressure to obtain the title compound (133 mg, yield 87%). The NMR data and ESI / MS data of this compound are shown below. 1H-NMR (400MHz »DMSO-d6) (5 (ppm): 1.97 (pent? J = 7.05 2H), 2.23 (t, J = 7.4, 2H), 3.91 (s, 3H), 4.50 (t, J = 6.8, 3H), 7.91 (d, J = 3.6; 1H)? 8.04 (s? 1H) 9 8.2 4 (s? 1H)? 12.11 (s? 1 H), 1 2.1 7 (d, J = 3.6, 1 H). ESI / MS m / e: 3 3 6.2 (M + + H, C) 4H14C1N503) -327- 200526665 (323) Example 5 7 4- [6-chloro-7- (1-methylpyrazole -4-yl) -4-oxy (pyrrolidine [3,2-d] pyrimidin-5-yl)]-N-[(4-tolyl) methyl] fluorenyl butyrate (compound number: 2507 ) 'S synthesis H3C. Μ

Add 4-methylbenzylamine (29mg) and diisopropylethylamine (84 μΐ) to a solution containing 4- [6 · chloro-7- (1-methylpyrazol-4-yl) -4-oxo Propyl-3-hydropyrrolo [3 '2-d] pyrimidin-5-yl] • butyric acid (40 mg) in a solution of N, N · dimethylformamide (1 m 1). Then, 0- (7-azabenzimidazol-1-yl) -N, N, N ', N, tetramethyluronic acid hexafluorophosphate (55 mg) was added, and the mixture was stirred at room temperature overnight. Ethyl acetate and 1 mol / 1 aqueous citric acid solution were added to the reaction mixture, and separated into two layers. The organic layer was washed with a saturated sodium bicarbonate aqueous solution and a saturated sodium chloride solution, dehydrated with sodium sulfate, and after filtering off sodium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (67 mg, yield, quantitative). Use without further purification to provide subsequent reactions. The ESI / MS data of this compound are shown below. ESI / MS m / e: 4 3 9.2 (M + + H »C 2 2 Η 2 3 C 1N 6 Ο 2) Example 5 8 4- [6- (3,4 · dimethoxyphenyl) methyl Pyrimidine • 328- 200526665 (324) azole-4-yl) -4-oxy (3-hydropyrrole [3,2-d] pyrimidin-5-yl)]-N- [(4-tolyl) Synthesis of methyl] ammonium butyrate (compound number: 2345) H3C, m State ·

Will contain 4- [6-chloro-7- (1-methylpyrazol-4-yl) -4-oxy (3-hydropyrrole [3,2-d] pyrimidin-5-yl)]-N -[(4-Tolyl) methyl] butyramide (65 mg), 3,4-dimethoxyphenylboronic acid (81 mg) and potassium acetate (73 mg) of N, N-dimethylformamidine The amine / water (2: 1) solution (2 ml) was degassed and replaced with nitrogen. A small amount of a complex of [1,1, -bis (diphenylphosphino) ferrocene] palladium (II) chloride methylene chloride (1: 1) was added. The reaction mixture was heated in a microwave oven at 160 ° C for 4 5 minutes. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (5-8% methanol / ethyl acetate), and then purified by fractional HPLC to obtain the title compound (4.4 mg, yield 7%). The HPLC retention time, NMR data and ESI / MS data of this compound are shown below. HPLC holding time = 8.2 (minutes)] H-NMR (400 MHz, CD30D) 5 (ppm): 1. 9 8 (m, 2 Η), · 2 · 1 3 (t, J = 7.5, 2H), 2.29 (2,3H), 3.79 (s, 3H), 3.82 (s, 3H), 3.91 (s, 3H), 4.18 (s, 2H), 4.36 (t, J = 7.4, 2H) 5 6.9 8 ( m, 2H), 7.07 (m, -329- 200526665 (325) 4H), 7.12 (d, J = 7.9, 1H), 7.28 (s5 1H), 7.66 (s, 1H), 7.97 (s, 1H). ESI / MS m / e: 541.1 (M + + H, c30H32N6O4) Example 59 4- (6 · cyclopropyl-4-oxy-3-hydropyrrole [3,2-d] pyrimidin-5-yl) Synthesis of ethyl butyrate (compound number: 2 5 08)

The title compound was obtained in the same manner as in Example 45 using ethyl 4- [3-amino-5-cyclopropyl-2- (ethoxycarbonyl) pyrrolyl] butyrate hydrochloride. The HPLC retention time and ESI / MS data of this compound are shown below. H-NMR (400MHz 'DMSO-d6) δ (ppm): 0.7 4 (m? 2H), 100Cm, 2H), 1.13 (t, J = 7.2, 3H), 1.93-2.06 (m, 3H), 2.31 ( t, J = 7.4, 2H), 3.98 (dd, J = 7.2, J = 14.2, 2H), 4.52 (t, J = 7.0, 2H), 6.0 ((1H), 7.71 (s5 1H) , 11.76 (brs, 1H). ESI / MS m / e: 290.2 (M + + H, C16H] 9N303) Example 60 4- (6-cyclopropyl · 7-iodo-4-oxy-3-hydropyrrole [3 2_d] pyrimidine- Synthesis of 5-yl) ethyl butyrate (compound number: 2509) 200526665 (326)

〇Contains 4- (6-cyclopropyl-4-oxy-3-hydropyrrole [3'2-d] pyrimidin-5-yl) butyric acid ethyl ester (1.58g) and N-iodine-number A solution of imine (1.35 g) in dichloromethane (40 ml) was patted and stirred at room temperature for 2 hours. Add water and stir for another 30 minutes. The solid was collected by filtration, washed with water and ethyl acetate, and dried under reduced pressure to obtain the title compound (1.82 g, yield 80%). The filtrate was separated into an ethyl acetate layer and an aqueous layer, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with saturated brine, and dehydrated with magnesium sulfate. After the magnesium sulfate was filtered off, the solvent was distilled off under reduced pressure. The resulting solid was collected by filtration, washed with ethyl acetate, and then dehydrated under reduced pressure to obtain the title compound (0.3 5 g, yield 15%). The NMR data and ESI / MS data of this compound are shown below. ! Η-NMK (400MΗζ ^ DMSO-d6) 5 (ppm): 0.89 (m, 2Η), 1.08-5H), 1.80 (m, 1H), 2.01 (m, 2H), 2.31 (t5 J = 7.3 , 2H), 3.96 (dd, J = 7.0? J = 14.3, 2H)? 4.57 (t? J = 7.2? 2H)? 7.82 (s, 1H), 12.00 (brs, 1H). ESI / MS m / e, 416.1 (M + + H 'C15H) 8IN303) Example 61 4- (6-Cyclopropyl-4-oxy-7 · (3-pyridyl) -3_hydropyrrolidine [ Synthesis of 3,2-d] pyrimidin-5-yl) butyric acid ethyl ester (compound number: 25 1 0) -331-200526665 (327)

〇 According to the same method as in Example 28, ethyl 4- (6-cyclopropyl-7-oxy-3_hydropyrrole [3,2-d] pyrimidin-5-yl) butyrate and 3 · boronic acid were used. Thus, the title compound was obtained. The NMR number and ESI / MS data of this compound are shown below.

1 H-NMR (400MHz, DMSO-d6) δ (ppm): 0.3 1 (m5 1.01 (m5 2H)? 1.13 (t5 J = 7.2? 3H)? 2.06-2.13 (m? 3H) 9 2. J = 7.3 , 2H), 3.98 (dd, J = 7.2, J = 14.25 2H), 4.61 (t, J 2H), 7.43 (ddd, J = 0.8, J = 4.89 J = 7.9? 1H), 7.82 (s5 8.01 (dt ; J = 2.0, J = 8.1, 1H), 8.46 (dd, J = 1.7, J = 4.7, 8.83 (dd? J = 0.8? J = 2.3, 1H), 1 1.99 (brs, 1H). ESI / MS m / e: 3 67.2 (M + + H, C20H22N4O3) Example 62 4- (6-cyclopropyl-7-iodo-4-oxy-7- (3-pyridine 3 3-hydropyrrole [ Synthesis of 3,2-d] pyrimidin-5-yl) butyric acid (compound I 23 63) -4 • • pyridine, 2H), 40 (t5 = 7.2, 1H), 1H),)-code: -332- 200526665 (328)

Add 1M lithium hydroxide aqueous solution (7.3ml) to the solution containing 4- (6-cyclopropyl-4-oxy-7- (3-pyridyl) -3-hydropyrrole [3,2-d] pyrimidine · 5 -A solution of dioxane (1.06 g) in dioxane (25 ml) and water (10 ml) was stirred at room temperature for 3 hours. After 1 M hydrochloric acid (10.2 ml) was added dropwise, the solvent was distilled off under reduced pressure. Ethanol was added to the residue, and the solid matter was collected by filtration, washed with ethanol, and dried under reduced pressure to obtain the title compound (1.10 g, quantitative yield). The NMR data and ESI / MS data of this compound are shown below. ] H-NMR (400MHz, DMSO-d6) S (ppm): 0.3 9 (m, 2H),

1.10 (m, 2H), 2.07 (m, 2H), 2.18 (m, 1H), 2.33 (t, J = 7.4, 2H), 4.63 (t, J = 7.3, 2H), 7.95 (s, 1H), 8.10 (dd, J = 5.7, J = 8.1, 1H), 8.82 (m, 2H), 9.16 (d, J = 1.8, 1H), 12.26 (brs, 1 H). ESI / MS m / e: 3 3 9 · 0 (M + + H, C 18 H 18 N 4 O 3 H C1) Example 63 4- (6 -cyclopropyl · cardioxy-7- (3- Dftn amidyl) (3-Hydropyrrolo [3,2-d] pyrimido-5 ** yl))-N _ [(4-Tolyl) methyl] sulfanyl butyrate (compound number: 2 3 3 1 Synthesis) -333- 200526665 (329)

CH3 was added with diisopropylethylamine (70 μΐ) and 4-methylbenzylamine (15mg) in a mixture containing 4- (6-cyclopropyl-4-oxy-7- (3-pyridyl) -3- Pyrrolidine hydrochloride [3,2-d] pyrimidin-5-yl) butyric acid hydrochloride (30 mg) and 0- (7-azabenzimidazol-1-yl) -N, N, N ' N'-tetramethyluronic acid hexafluorophosphate (46 mg) in a solution of N, N-dimethylformamide (1.5 ml). The reaction solution was stirred at room temperature for 4 hours. The solvent was distilled off under reduced pressure. The residue was added with ethyl acetate and water and separated into two layers. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dehydrated with sodium sulfate, sodium sulfate was filtered off, and then the solvent was distilled off under reduced pressure. The residue was purified by fractional HPLC to obtain the title compound (3.1 mg, yield 9%). The HP LC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC holding time = 7.3 (minutes)] H-NMR (400MHz, DMSO-d6) (5 (ppm): 0.27 (m, 2H), 0.93 (m, 2H), 2.01-2.ll (m, 3H), 2.21-2.27 (m, 5H), 4.21 (d, J = 5.9? 2H)? 4.58 (t, J = 7.1, 2H), 7. 10-7. 15 (m? 4H), 7.43 (ddd, J = 0.8, J = 4.85 J = 7.9, 1H), 7.82 (s5 1H), 8.01 (dt, J = 2.0, J = 8.1, 1H), 8.34 (t, J = 5.9, 1H), 8.46 (dd, J = 1.8, J = 4.8, 1H), 8.84 (dd5 J = 0.8? J = 2.3; 1H). ESI / MS m / e: 442.2 (M + + H, C26H27N502) -334- 200526665 (330) Examples 64 4- [6-Cyclopropyl-7- (1-methylpyrazol-4 · yl) -4-oxy-3-hydropyrrole [3,2-d] pyrimidin-5-yl] butanoic acid Synthesis of ethyl ester (compound number: 25 1 1)

HqC, μ

Following the same method as in Example 28, ethyl 4- (6-cyclopropyl-7-iodo-4-oxy-3-hydropyrrole [3,2-d] pyrimidin-5-yl) butyrate and 1 -Methyl_4- (4,4,5,5-tetramethyl-1,3,2-dioxyborane-2-yl) -1H-D-pyrazole to give the title compound. The NMR data and ESI / MS data of this compound are shown below. 1H-NMR (400MHz, DMSO-d6) δ (ppm): 0.5 1 (m5 2H), 1 · 1 3 (m, 5 H), 1 · 9 1 (m, 1 H), 2.0 3 (m, 2 H), 2 · 3 1 (t, J = 7 · 3, 2H), 3.89 (s5 3H), 3.97 (dd, J = 7.25 J = 14.2, 2H), 4.58 (t, J = 7.0, 2H), 7.80 (d, J = 3.3, 1 H), 7.8 3 (d, J = 0.7, 1H), 8.03 (s, 1H); 1 1.87 (brs, lH) o ESI / MS m / e: 3 70.2 (M + + H, C19H23N5 03) Example 65 4- [6-Cyclopropyl-7- (1-methylpyrazol-4-yl) -4 -oxy-3-hydropyrrole [3,2 -d] Synthesis of pyrimidin-5-yl] butyric acid (Compound No .: • 335- 200526665 (331) 2364)

H3C, n1 &lt; N

A 1 M aqueous lithium hydroxide solution (3.5 ml) was added dropwise to a solution containing 4- [6-cyclopropyl-7- (1-methylpyrazol-4-yl) -4-oxy-3-hydropyrrolidine [3 2,5-d] pyrimidin-5-yl] butyric acid ethyl ester (0.52 g) in a dioxane / water (4/1) solution (25 ml), the reaction solution was stirred at room temperature, and then added dropwise. 1M hydrochloric acid (3.5ml). The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane / methanol / acetic acid / water = 240/30/3/2), and diethyl ether was added to the obtained solid to be crushed. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to obtain the title compound (0.40 g, yield 84%). The NMR data and ESI / MS data of this compound are shown below. 1H-NMR (400MHz, DMSO-d6) o (ppm): 0.5 1 (m? 2H)? 2H),]. 8 8-2.02 (m, 3H), 2.23 (t, J = 7.4, 2H), 3.89 (s, 3H)? 4.57 (t? J = 7.2? 2H)? 7.80 (d, J = 3.5? 1H) 9 7.8 3 (d? J = 0.7? 1H), 8.03 (s5 1H), 1 1.87 (brs , 1H). ESI / MS m / e: 3 4 2 · 2 (M + + H, C 17 H i 9 N 5 0 3) Example 66 4- [6-Cyclopropyl-7- (bumethylpyrazole-4 · yl ) -4-oxy (3-hydropyrrole [3,2-d] pyrimidin-5-yl)]-N-[(4-tolyl) methyl-336- 200526665 (332)

Synthesis of methyl] ammonium butyrate (compound number: 2332) H3C &gt; m ^ N

CH, 〇 Add diisopropylethylamine (78 μΐ) and 4-methylbenzylamine (13mg) to 4- [6 · cyclopropyl-7- (1-methylpyrazol-4-yl) -4-oxy-3-hydropyrrole [3,2-d] pyrimidin-5-yl] butanoic acid (30 mg) and 0- (7-azabenzimidazol-1-yl) -N, N In a solution of N, N'-tetramethyluronic acid hexafluorophosphate (40 mg) in N, N-dimethylformamide (1.0 μΐ), the reaction solution was stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was purified by fractional distillation HPLC to obtain the title compound (30 mg, yield 77%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 8.0 (minutes) ESI / MS m / e: 445.3 (M + + H, C25H28N602) Example 67 5 -Benzyl-7- (1-oxy (3-pyridyl))- Synthesis of 3-Hydropyrrolo [3 '2-d] pyrimidin-4-one (Compound Number: 2499) -337- 200526665 (333)

Add 30% hydrogen peroxide solution (92mg) to the solution containing 5-benzyl-γ-ί 3-pyridyl &gt; -3-hydropyrrolo [3, 2-d] pyrimidin-4-one (3 lmg) In an acetic acid (2 m 1) solution, stir overnight at 50 ° C. The reaction mixture was cooled to room temperature, and purified by fractional HPLC to obtain the title compound (19 mg, yield 58%). The HPLC retention time, NMR data, and ESI / MS data of this compound are shown below. HPLC retention time = 5.8 (minutes) 1H-NMR (400MHz ^ DMSO-d6) δ (ppm): 5.64 (s? 2H), 7.24-7.35 (m, 5H), 7.46 (m, 1H), 8.00 (m, 2H), 8.10 (m, 1H), 8.34 (s, 1H), 9.11 (s, 1H), 12.25 (brs5 1H). ESI / MS m / e: 319.3 (M + + H'C] 8H] 4N4 02) Example 68 (Third butoxy) -N- {2- [6- (3-chloro (2-thienyl) ))-7- (5-methyl (1,2,4-oxydifluoren-3-yl))-4-oxy (3-aminoammonium glutamate [3 'meridine-5- Base)] B $} 醯 0 Female (Chemical Compound Number: 2 1 26) Synthesis -338-200526665 (334)

CH3 ι. N

Dissolved (Third Butoxy) -N- {2- [6- (3-chloro (2-thienyl))-7-cyano-4-oxy (3-hydropyrrole [3,2-d ] Pyrimidin-5-yl]] ethyl} amidamine (105 mg) in ethanol (2.5 ml), hydroxylamine hydrochloride (35 mg), diisopropylethylamine (100 mg) were added, and reflux was superheated Stir overnight. The solvent was distilled off under reduced pressure, dichloromethane (2.5 ml) and water (2.5 ml) were added, and the organic layer was separated. The aqueous layer was further extracted with dichloromethane (2.5 ml). After the organic layer was dehydrated with sodium sulfate, the solvent was distilled off under reduced pressure to obtain a residue (3 mg). The residue was dissolved in dichloromethane (2 ml), and acetic acid (18 mg), 1-ethyl-3- (3, dimethylaminopropyl) carbodiimide hydrochloride (57 mg), and triethylamine (41 μΐ), and stirred at 40 ° C for 1 hour. The reaction solution was concentrated, and then purified by fractional distillation of P L C to obtain the title compound (7.2 mg, yield 6%). The HPLC retention time and ESI / MS data of this compound are shown below. HPLC retention time = 9.5 (minutes) ESI / MS m / e: 476.9 (M + + H, C20H21ClN6O4S) Example 69 (third butoxy) -N · {2- [6- (3 · chloro (2- (Thienyl))-7- (1,2,4-oxydiazol-3-yl) -4-oxy (3-hydropyrrole-339- 200526665 (335) 骈 [3,2-d] pyrimidine- Synthesis of 5-yl)] ethyl} amidamine (compound number: 2513)

H3C CH3 Soluble (third butoxy) -N- {2- [6- (3 · chloro (2 · thienyl))-7-cyano-4-oxy (3-hydropyrrole [3,2 -d] pyrimidin-5-yl)] ethyl} amidamine (105 mg) in ethanol (2.5 ml), hydroxylamine hydrochloride (35 mg) was added, and diisopropylethylamine (100 mg) was added in Stir overnight under superheated reflux. The solvent was distilled off under reduced pressure, dichloromethane (2.5 ml) and water (2.5 ml) were added, and the residue was separated into a dichloromethane layer and an aqueous layer to obtain an organic layer. The aqueous layer was extracted with dichloromethane (2.5 ml), and the combined organic layer was dehydrated with sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a residue (113 mg). On the other hand, N, N-dimethylformamide (40 mg) was dissolved in diethyl ether (1 ml), and phosphoric acid chloride (84 mg) was added, followed by stirring at room temperature for 1 hour. The resulting oil was diethyl ether ( 1 ml), washed twice, and suspended in a mixed solution of 1, [dioxane and diethyl ether (3 ml). This suspension was added to the above residue and stirred at room temperature for 2 hours. After the reaction solution was concentrated, water (5 ml) and ethyl acetate (5 ml) were added, and the organic layer was separated. The aqueous layer was further extracted with ethyl acetate (5 ml). The combined organic layer was concentrated and purified by fractional distillation of hplC to obtain the title compound (1.9 mg 'yield: 1.6%). The HPLC retention time and ESI / MS data of this compound -340- 200526665 (336) are shown below. HPLC retention time = 9.1 (minutes) ESI / MS m / e: 462.9 (M + + H, C19Hi9C1N6〇4S) Example 70 (third butoxy) · N- {2- [6- (3-hydroxybenzene (Synthetic) -4-oxy-7- (3-pyridyl) (3-hydropyrrole [3,2-d] pyrimidin-5-yl)] ethyl} fluorenamine (compound number: 2121)

Dissolving (Third Butoxy) -N- (2- {4-oxy-6- [3- (phenylmethoxy) phenyl] -7- (3-pyridyl) (3-hydropyrrole) [3,2-d] pyrimidine-5yl)} ethyl) fluorenamine (8.0 mg) in ethanol, and palladium on carbon (20 mg) were added. The reaction was replaced with hydrogen, and stirred at 60 ° C overnight under a hydrogen atmosphere of 1 atmosphere. After the reaction solution was cooled to room temperature, palladium on carbon was filtered off. The filtrate was concentrated and purified by fractional HPLC to obtain the title compound (4.0 mg, yield 60%). The HPLC retention time and ESI / MS data of this compound are shown below. HPLC retention time = 6.3 (minutes) ESI / MS m / e: 448.0 (M + + H, C24H25N504) Example 7 1 to 4 9 4 200526665 (337) According to any one of the methods of Examples 1 to 70 above 'The following compounds of the present invention were synthesized using the corresponding raw material compounds and reactants, respectively. The ESI / MS data in the HPLC / mass spectrometry of each compound, the retention time and purity of the compounds in the HPLC analysis under the following analysis conditions, the synthesis method used and the corresponding compound numbers are shown in Table 2. The compound numbers in the table represent the compound numbers in Table 1 listed in the foregoing specific examples.

-342- 200526665 (338) Table 2 Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis 71 19 Cj »Hjn Ns 〇2 352.2 5. · 7 96 Example 40 72 27 〇2β H25 Νδ 〇3 456.3 7.8 99 Example 40 73 29 C-J7 Ηΐ7 Νδ 〇2 324.2 3.3 99 Example 40 74 40 c21 h15 ci2 n7 0 s 484.2 7.7 98 Example 38 75 80 C20 H14 Br Cl N6 〇S 503.2 6.8 100 Example 38 76 83 〇2β His Cl Ng S2 515.4 10.4 96 · Example 38 77 212 CiB H14 Cl Ns 0 s 395.4 11.7 86 Example 28 78 219 C20 H-te Cl N5 〇2 S 428.0 5.6 95 贲 Example 35 79 230 C21 H20 Cl N5 〇2 S 442.4 4 6.5 100 Example 37 80 245 C21 h2〇Cl n5 o2 s 442.0 6.1 94 Example 35 81 254 C22 H22 Cl N5 〇2 s 456.1 1 6.9 95 Example 35 82 2S7 〇2ΐ H23 N5 〇2 378.2 4.3 100 贲 Example 36 83 263 C20 H21 N5 〇2 364.2 10. 0 96 Example 35 84 269 C21 Ητβ ci N5 02 S 440.4 6.2 100 Example 37 85 280 C22 H25 Ns 〇 2 392.2 5.4 100 Example 35 86 287 C23 H22 Cl N5 〇2 s 468.0 7.1 95 Example 35 87 288 〇22 H21 Cl N4 〇2 S2 472.9 1L8 97 Example 35 88 297 C23 H27 Ns 〇2 406.2 12.9 98 Example 35 89 303 C24 H24 Cl Ns 〇2 s 482.4 8.8 100 Example 37 90 321 C19 H * I3 Cl F3 N5 〇2 S 468.4 7.3 99 Implementation Example 37 91 330 C22 H2i Ng 〇2 400.5 5.0 99 Example 35 92 347 C25 HnB Cl F N4 〇s2 509.4 15.0 99 Example 37 93 348 C24 H17 ci F N5 〇2 s 494.2 8.0 100 Example 37 94 361 〇2e H20 Cl N5 O4 S 534.0 9.4 78 賨 Example 35 95 370 〇2〇H ^ 3 Br Ol F3 Να O3 S 563.1 1 10.4 100 Example 35 -343- 200526665 (339) Example number Compound number Composition formula ESI / MS m / e HPLC min purity (%) synthetic method 96 492 〇〇23 H23 CI Νβ 〇2 S 483. 1 10.8 93 贲 Example 33 97 504 C24 H25 Cl Ne 〇2 S 497.5 8.6 84 Example 33 98 536 C30 H27 Cl Ng 〇s S 587.4 9.0 79 Example 33 99 595 〇21 H2S N5 〇2 380.2 5.2 100 Example 35 100 596 C22 H22 Ol N5 〇2 s 456, 1 6.9 98 Example 35 101 601 C21 H25 N5 〇2 380 2 5.3 100 Example 35 102 602 C22 H22 Cl Ns 〇2 S 456.1 1 7.1 94 Example 35 103 605 C22 H29 N5 〇2 396.3 5. · 1 1 00 Example 35 104 615 C22 H27 N5 〇2 394.1 1 7.5 99 Example 35 105 616 H26 N4 〇3 383.2 10.3 • 78 Example 28 106 617 C21 Hjg N4 〇2 S 399.1 1 li, 6 87 Example 35 107 618 C20 H26 Ng 〇2 383.2 8. 1 60 Example 28 108 627 C22 H23 Cl N4 O3 S 459.3 15.0 95 Example 35 109 628 C22 H2S Cl N4 〇2 S2 475.2 15.7 100 Example 35 110 634 C22 H27 Νδ 〇 2 394.2 5.7 100 Example 53 111 641 C23 H27 Ng 〇2 406.2 5.9 100 Example 35 112 646 C24 H24 Cl N5 〇2 S 482.0 6.9 95 Example 35 113 657 C2i H23 N6 〇2 378.3 4.3 97 Example 35 114 659 C22 H20 Cl N5 〇2 s 454.1 1 6.5 94 Example 35 115 664 C23 H24 Cl N5 〇2 s 470 · 2 9. 1 99 Example 35 116 667 〇24 H28 N5 〇2 420.2 6.3 100 Example 36 117 668 〇25 H26 Cl N5 〇2 S 496.0 0 8.3 8.5 80 Example 36 118 668 〇2 £ H26 Cl Ns 〇2 s 496.0 8.3 89 Example 36 119 673 C25 H26 Cl N5 O3 S 512.0 6.6 6.9 98 Example 36 120 678 〇2Β H32 Cl N5 〇2 S 538. 1 11 · 1 97 Example 36

• 344- 200526665 (340) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 121 689 ^ 25 H25 Cl Ne 〇3 S 525.0 5-9 78 Example 36 122 694 〇24 Η29 Ng 〇2 420.2 2 6.6 100 Example 35 123 696 〇25 H26 Cl 1 ^ 5 〇2 S 496.0 0 8.5 98 Example 35 124 702 Ci9 H2I N5 O3 368.2 9.5 82 Example 35 125 704 C20 Hie Cl N5 〇3 s 444.0 5.4 87 Example 35 126 709 C21 H21 Cl Ne 〇2 s 457.1 4.8 94 Example 35 127 713 C21 Hie Cl ΝΙβ O3 S 471.0 5.2 85 Example 30 128 718 C22 H20 Cl Ns 〇as 486.0 6 ′ 90 Example 35 129 723 ^ 2Λ H23 Nj 〇2 414.5 5.0 98 Example 35 130 724 C25 H20 Cl N5 〇2 s 490.4 8.1 100 Example 37 131 729 〇25 H20 Cl N5 〇3 S 506,0 8.0 90 Example 35 132 733 ^ 25 H25 N5 〇2 428.0 6.7 98 Example 35 133 734 C26 H22 Cl N5 〇2 s 504.0 8. 5 94 Example 35 134 741 C22 H20 Cl N5 〇2 s 454.0 5.7 87 Example 35 135 760 C20 H24 N® 〇2 381.1 5. 1 98 Example 32 136 768 C21 H21 Cl n6 o2 s 457.1 5.4 95. Example 32 137 770 〇20 H20 C 丨 M5 〇2 S2 461.9 10.9 9Θ Example 32 138 776 C24 H25 Cl Ne 02 S 497.0 7.7 95 Example 32 139 785 C23 H22 N $ 〇2 415.0 6.9 96 Example 32 140 795 〇23 Hia Cl N5 〇2 S2 495.9 12.1 99 Example 32 141 801 C24 Η1βCl F N6 02 S 508.9 7.9 97 賨 Example 32 142 802 C24 H18 Cl F Ne 〇2 s 508.9 8. 1 85 Example 32 143 803 CIj Ng 〇2 S 526 · 9 9. 1 95 Example 32 144 804 c25 h21 ct n6 〇3 s 520.9 7.7 98 Example 32 145 805 C25 H21 Cl Νβ 〇2 S 504.9 7.9 95 Example 32 -345- 200526665 (341) Example number Compound number composition Formula ESI / MS m / e HPLC min Purity (%) Synthesis method 146 806 〇25 H21 Cl Ng 〇2 S 504.9 8.2 85 贲 Example 32 147 807 C25 H21 Cl Ne 〇2 s 504.9 8.1 89 Example 32 148 808 H -jb CI2 Ne 〇2 S 520.8 9.3 97 Example 32 149 809 C24 H-ie CI2 Νβ 〇2 S 526 · 9 8. 7 96 Example 32 150 810 C24 H18 Cl F Ne 〇 2 S 508 · 9 7. 7 96 Example 32 151 811 C25 H2i Cl Ng O3 S 520.9 8.9 93 Example 32 1S2 812 〇25 H21 Cl Ne O3 S 520.9 7.4 99 Example 32 153 912 C22 N4 O3 349.5 9. 5 91 Example 28 154 915 C21 H25 N5 O3 396.3 5.5 98 Example 28 155 917 C20 H24 Nd 〇λ 385.3 10.9 66 Example 28 156 918 〇20 H24 N4 〇3 S 401.5 12.4 93 Example 28 157 948 C18 H21 Cl N. 03 S 409.2 11.4 82 Example 26 158 956 〇24 H25 Cl N4 〇3 s 485.2 13.9 91 Example 26 159 968 C23 Hj9 0) N4 〇3 S 477.3 12.9 95 Example 28 160 970 C19 Η1β Cl Ha 〇3 S 419.3 3 10.9 98 Example 27 161 972 C23 H27 Cl N4 O3 s 475.2 11.4 83 Example 27 162 973 C25 H30 Cl Ns 〇3 S 499.2 7.7 81 Example 27 163 974 C25 H23 Cl O3 s 495.5 10.9 98 Example 27 164 975 c25 H22 C) F N4 〇3 s 513.2 11.1 95 Example 27 165 976 〇2e H25 Cl O4 S 525.2 11. 0 98 Example 27 166 977 C25 H24 Cl Ns 〇3 s 510.2 7.9 28 Example 27 167 978 C25 H22 CI2 N4 O3 s 529.2 11.5 95 Example 27 168 979 〇24 H22 Cl N5 〇3 S 496.2 7. 9 72 Example 27 169 980 C24 H30 Cl Ns 〇3 S 488.3 3 7.5 92 Example 27 170 982 C22 H27 Cl N4 〇3 S Si 491.4 12.0 87 Example 27

-346-200526665 (342) Example number Weid number composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 171 983 〇23 H23 Cl 〇3 S 471.3 10.5 92 Example 28 172 984 C23 H22 ci F N &lt; 〇3 s 489.2 10.9 85 Example 28 173 985 C24 H22 Cl F3 N4 O3 s 539.2 12. 1 92 Example 28 174 986 〇2 H22 Cl F3 N4 O4 s 555.3 12 · 2 93 Example 28 175 987 C23 H22 CI2 N4 O3 S 505 · 1 11.6 95 Example 28 176 988 〇25 H25 Cl N4 〇4 s 513.3 9.8 88 Example 28 177 989 C2B H27 Cl N4 〇4 s 563.3 12.5 91 Example 28 178 990 C25 H27 Cl Team 〇5 s 531.3 9.5 91 Example 28 179 991 C25 ΗβCl N5 O3 s 514.2 7.3 79 Example 28 180 992 C2, H25 Cl N4 〇3 s 485.3 11. 1 94 Example 28 181 993 c27 H25 Cl N, 0a S 521.6-81 Example 28 182 994 C2S H27 Cl N4 03 s 499.2 11.6 96 Example 28 183 995 C21 H2l Cl n6 on s 473.2 8.0 22 Example 28 184 996 Cgg Hgs Cl N5 Ojj S 542.3 8.7 90 Example 28 185 997 ^ 29 H33 Cl N4 〇3 S 553.3 14. 0 88 Example 28 186 998 C22 H22 Cl N5 O3 s 472.2 6. 6 78 Implementation 28 187 999 ^ 22 H22 Cl N £ O3 S 472 · 4 8.0 97 Example 28 188 1001 Can Hjt Cl N4 O4 S 461.1 12, 5 84 Example 28 189 1002 C21 Η2Ί Cl O3 S2 477.1 1 13. 1 94 Implementation Example 28 190 1003 C23 H24 Cl N5 O4 s 502.0 11. 1 61 Example 28 191 1004 C23 Η 2Δ Cl Ns 04 S 502.0 11.5 71 賨 Example 28 192 1005 C23 H24 ci Ns 〇4 s 502.1 7. 7 93 Example 28 193 1006 C22 H21 CI2 O3 S 506.0 12 · 8 90 Example 28 194 1007 C22 H21 Cl F Ns 〇3 s 490.1 1 12. 1 80 Example 28 195 1008 C22 H21 Cl F Ns 〇3 s 490.1 1 12.8 94 28Example 28 • 347- 200526665 (343) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 196 1009 C26 H24 C! Ns 〇3 S 522.0 10.4 54 Example 28 197 1010 C24 H22 Cl N5 〇3 s 496.4 14.7 88 Example 28 198 1011 C23 H22 Cl F N4 O3 S 489.3 13.0 99 Example 28 199 1012 C23 H22 Cl F N4 03 S 489.4 13.3 96 Example 28 200 1013 C22 H23 Cl N4 O3 S2 491.3 12.9 99 Example 28 201 1014 〇2〇H21 Cl Νβ 〇3 S 461.4 8.9 98 Example 28 202 1106 C18 Hie N5 〇 2 338.4 5.1 97 Example 40 203 1131 C15 H15 N5 〇2 298.3 2.2 99 Example 40 204 1132 C * k H * | 3 N5 〇2 284.2 1.7 99 Example 40 205 1146 C * ie Ητδ N5 〇2 310.4 2.6. 99 Example 40 206 1161 C-1D Hi £ N5 〇 2346 · 2 5.9 96 Example 40 207 1168 C18 H23 N5 〇 2 354.3 7. 1 99 Example 40 208 1170 〇15 Ηκ N4 〇3, 299.2 4.4 96 Implementation Example 39 209 1174 C12 H10 N4 0 227.2 2.4 100 Example 28 210 1175 c12 h9 Cl n4 0 261.1 1 4.4 95 Example 41 211 1177 Cn He N4 0 213.1 1 5.0 99 Example 28 212 1179 C18 H-14 O 303.2 7.2 99 Example 39 213 1181 Cie H15 N7 0 358.1 1 3.6 100 Example 38 214 1182 c23 h18 ci n7 O s 474,0 6, 8 67 Example 38 215 1183 C22 H17 Cl Nfi 0 S 477. 1 7. 7 100 Example 38 216 1184 C23 H * j9 N7 〇410 · 3 2.3 100 Example 38 217 1185 C24 H1B ci n7 0 s 487.9 6.0 90 Example 38 218 1186 C22 h17 Cl Fa n7 0 s 520. 1 8. 1 100 Example 38 219 1206 C20 H * j9 Cl Ng 〇2 S 443.1 1 6.7 97 Example 35 220 1216 C21 H21 Cl Ne 〇2 s 457.0 8.6 87 Example 28

• 348 · 200526665 (344) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 221 1217 〇22 Hj3 Cl Ng 〇2 S 471.1 1 7.6 83 Example 35 222 1228 C23 H25 Cl Ne 〇2 s 485.2 8. 2 96 Example 35 223 1236 c25 h26 Cl n5 o2 s 497.9 8.4 96 Example 36 224 1237 H27 Cl Ng 〇2 S 499.2 8,5 99 贲 Example 36 225 1243 C25 H22 Cl F Ne 02 S 525.2 8.5 95 Example 35 226 1250 〇21 H23 Cl Ng 〇2 S 459.2 7.5 95 贲 Example 35 227 1257 C21 H23 OI Ne 〇2 S 459.2 7.6 98 Example 35 228 1258 Cie H24 Ng 〇2 357.2 5.9 100 Example 53 229 1259 C «te H23 C 丨 Ng 391.2 6.7 98 Example 50 230 1280 C21 H27 N5 〇 2 382.2 5.3 100 Example 53 231 1261 C20 H28 Νβ 〇2 385.3 6.4 96 Example 35 232 1262 C21H30Ns. 2 399.3 6.6 100 Example 35 233 1271 〇21 H2B Νβ 〇2 397.2 5.8 100 贲 Example 35 234 1277 C23 H2B Νε 〇3 437.3 7.6 79 Example 53 235 1278 C22 H2B Ne 03 423.2 7.2 100 Example 53 236 1282 C23 H2S N5 〇2 S 436.2 6. 0 95 Example 53 237 1284 〇22 ^ 26 Ne 〇2 S 439.2 7.5 100 Example 53 238 1286 C23 H ^ b ⑷ 〇2 S 453.2 8.0 100 Example 53 239 1287 C23 H24 Cl N5 〇3 s 486.3 6.7 100 Example 67 240 1288 C22 H25 Cl Ne 〇2 S 473.1 7 8 93 Example 35 241 1293 C23 H27 Cl N6 o2 s 487.1 8.6 100 Example 28 242 1296 〇23 H2B Ng 〇2 S 453.2 8.1 95 Example 53 243 1297 C21 H25 N5 〇2 380.2 5.2 96 Example 53 244 1331 C23 H27 N7 〇2 434.2 5.2 100 贲 Example 53 245 1332 C22 H2B Nb 〇2 437.3 5.9 100 寊 Example 53

-349- 200526665 (345) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthetic method 246 1333 〇2β Η32 Νε 493.2 7. 1 81 Example 53 247 1334 〇25 ^ 26 Ng 〇 4 477.2 7.5 100 Example 53 248 1335 〇25 H25 Νδ 〇 03 420.2 5.6 99 Example 53 249 1337 〇22 Η2β Me 〇3 423.2 7.1 100 Example 53 250 1338 〇22 Hig Νβ 〇2 S 439.2 7.6 98 Example 53 251 1341 〇23 H2fi Ne 〇2 S 453.2 8.3 100 Example 53 252 1364 〇2Ί Η23 Ns 〇2 378.3 4.3 98 贲 Example 35 253 1374 C21 H21 Cl Νβ 02 S 457.1 1 7. 1 96 Example 35 254 1399 C23 H25 Cl 〇2 S 485.2 8. 0 92 Example 36 255 1405 C24 H2B N5 〇2 420.2 6.1 100 Example 36 256 1413 C25 H26 Cl Ns 〇2 S 497.9 9 8.7 96 Example 36 257 1415 C2. H27 Cl Ne 02 S 499.1 8.6 100 Example 36 258 1423 c25 H3! N5 〇2 434.4 6.5 98 Example 36 259 1427 C25 H29 Cl N © 〇2 S 513.2 9.3 96 Example 36 260 1430 C21 H2n Cl N6 〇2 S 457. 1 7.1 89 Example 35 261 1445 C24 H27 Cl Ne 〇2 S 499.2 8.8 100 Example 36 262 148 2 C25 H31 N5 〇2 434.4 4 6.8 96 Example 35 263 1486 〇25 H29 Cl Ne 〇2 s 513.2 「9.5 100 Example 36 264 1490 C22 H27 Ng 〇2 394.4 5.4 98 Example 35 265 1494 C22 H25 Cl N6 O2 s 473.2 8.2 98 Example 35 266 1511 C ^ e H23 Cl N $ 〇 2 S 519. 1 6.5 91 Example 33 267 1514 C21 h19 0 n6 o2 s 455.1 6.9 87 Example 35 268 1519 C20 H23 N5 〇2 S 398.2 4.9 100 Example 36 269 1520 〇21 H20 Cl N5 〇2 S2 474.0 5.3 98 Example 35 27Q 1522 C24 H25 Cl Νβ 〇3 S 513.1 4.2 100 Example 36 -350- 200526665 (346) Example number Compound number composition Formula ESI / MS m / e HPLC min Purity (%) Synthesis 271 1530 C2S H27 Cl Ne 02 S 512.9 5.4 92 Example 36 272 1533 C2HuCl F, Ns 02 S 500.0 0 6.3 65 Example 35 273 1535 C21 h13 ci f7 n5 o2 s 568.0 7 · 96 96 Example 35 274 1549 C25 H31 N5 〇2 434.2 6.8 100 Example 35 275 1553 C25 H29 CI Ne 〇2 s 513.2 9.5 90 Example 35 276 1554 C26 Ηβ3 N $ 〇2 448.2 7.5 100 Example 35 277 1558 C26 H31 Cl Νβ 02 S 527.2 10.3 95 Example 35 278 156 6 C24H25C1N802S 497.2 8.3 97 Example 36 279 1589 〇23 H25 F2 N5 〇2 442. 23 5. 3 98 Example 36 280 1600 C23 H23 Cl Fj Ne 〇2 S 521.2 7.8 98 Example 36 281 1623 〇27 H35 N5 〇 2 462.2 7.5 7. 7 100 Example 35 282 1647 C24 H26 F3 N5 〇2 474.2 6.2 6.5 79 Example 36 283 1654 C24 H24 Cl F3 Ng 〇2 S 553.2 9.1 1gg Example 36 284 1660 C25 H31 N5 〇2 434.3 3 6.5 6.6 99 Example 36 285 1661 C26 H29 Cl Ng 〇 2 S 513.2 2 9.3 9.4 98 Example 36 286 1673 C22 H25 N5 O3 408.2 4.5 100 Example 36 287 1679 C22 H23 Cl Ne 〇3 S 487. 1 6.4 95 Example 36 288 1682 〇2β H31 Cl Ng O4 S 583.2 6.9 96 Example 36 289 1691 C28 H31 Cl Ne 0. S 583.2 6.9 98 Example 36 290 1693 C27 H32 C! N7 0 &lt; S 586.2 8.4 95 Example 36 291 1695 C27 h32 Ci N7 Ολ s 586.2 8. 6 95 Example 36 292 1696 C2fi H31 Ci Ne 〇AS 583 · 1 7.0 99 Example 36 293 1697 C27 H32 Cl N7 04 S 586.2 8.6 94 Example 36 294 1698 C26 H3〇Cl N7 〇4 s 572. 1 7 · 8 93 Yin Example 36 295 1699 C27 H2S Cl Νβ 〇4 S 569.1 6.2 98 Example 36 -351-200526665 (347) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 296 1700 c26 h3oci n7 o. S 572.2 7.8 92 Example 36 297 1715 C29 H33 Cl N6 〇3 s 581.2 6.3 93 Example 36 298 1719 C27 H27 ci Ne 〇3 S 551 · 1 5.2 96 Example 36 299 1721 〇26 ^ 29 Cl Ng 〇3 S 565, 2 5.7 93 Example 36 300 1739 c27 h31 ci n6 〇2 s 539.2 4.7 90 Example 36 301 1748 H33 C 丨 Ne 02 S 553.2 5.1 95 Example 36 302 1751 ^ 8ΚΙ330ΙΝβ02Β 553.2 5.2 96. Buy Example 36 303 1753 C29 H35 Cl Ns 〇2 S 567.2 5 · 5 89 Example 36 304 1758 C27 His Cl Ne 〇 2 S 537 · 1 4.7 96 賨 Example 36 305 1778 C25 H22 f3 n5 o2 482.3 6.5 99 Example 36 306 1804 C27 H21 Cl N6 〇2 s 530. 9 7.4 92 霣 Example 36 307 1805 C28 H23 Cl Me 〇2 S 543.1 8.1 89 Example 36 308 1806 C27 H22 Cl Ns 〇2 s 516.1 1 6.8 96 Example 35 309 1808 C27 H22 Cl N5 〇2 s 518.0 8 1 90 Example 36 310 1823 C28 H23 Cl Ne 〇2 s 519.1 5.2 94 贲 Example 36 311 1828 c27 h25 ci n6 o2 s 533.1 5.2 89 Example 36 312 1833 C26 H21 Cl Ne 〇2 S 517.1 5.9 86 Yin Example 36 313 1843 C23 H25 Ns O3 419.2 4. 6 86 Example 36 314 1846 Cje H27 N5 〇2 441.2 6.1 90 Example 30 315 1849 C28 H36 N6 〇4 520.3 6.3 39 Example 36 316 1852 C29 H38 Νβ 〇4 534.3 6.9 43 Example 36 317 1855 C16 Hne Fg N5 〇2 406.2 4.4 98 Example 36 318 1860 c19h16cifa〇.s 485.1 7.4 91 Example 36 319 1861 C18 H-Jg Cl Fj N5 〇2 408.2 4.9 36 Example 36 320 1865 C20 H22 Ct 〇2 400.3 4. 6 60 Example 35 -352- 200526665 (348) Example number Wei number composition formula ESI / MS m / e HPLC min Purity (%) Synthesis 321 1868 〇2ι H23 N5 〇2 378.3 4.4 97 Example 35 322 1885 C20 Hgo Fs N5 〇2 420.1 1 5.0 100 Example 36 323 1890 C20 H ^ b Cl F3 Ng 〇2 S 499.1 1 7.7 98 Example 36 324 1891 C24 H29 N5 〇2 420.2 6.3 100 贲 Example 36 325 1894 〇24 H27 Cl Ne 〇2 S 499.2 9.0 100 Example 35 326 1899 G21 H22 F3 NU 〇2 434.1 1 5.5 100 Example 36 327 1900 C21 H20 CI f3 n6 o2s 513.1 1 8.2 98 贲 Example 36 328 1913 〇2l H2〇Ne 〇2 389.1 1 100 100 Example 36 329 1915 〇21 H21 CI2 N5 〇2 446.1 1 5.5 100 Example 36 330 2003 ^ 24Η27 ^ 1Nβ〇2 467.2 8.6 70 Example 53 331 2004 C20H2s Ns 〇2 440.5 6.0 99 Example 35 332 2005 C22 H23 Cl Ng 〇2 S 471.0 7.2 97 Example 32 333 2006 C23 H23 Cl N5 〇2 S 483.0 7.4 97 Example 32 334 2007 C24 Hnj Fa N® 〇 2 483.3 7.0 99 Example 32 335 2008 C24 H2l f3 n6 o3 499.3 7.1 96 Example 32 336 2009 〇23 H * j7 CI2 N7 〇2 S 526.0 6.5 90 贲 Example 33 337 2010 C25 H20 ci F Ne 〇2 s 523.1 6.3 97 Example 32 33S 2011 H21 Cl F N7 02 S 526.1 1 7.9 97 Example 32 339 2012 Hgo Cl N7 〇 2 S 506.1 4. 0 81 Example 33 340 2013 C25 H23 F3 N5 O3 513.1 6.8 100 Example 32 341 2014 c25 h27 Cl nb o2 s 511.0 9.4 97 Example 32 342 2015 Cu H2b Cl Nr 〇2 S 514.1 8.5 100 Example 32 343 2016 C25 H21 Cl n8 o2 s 505.0 7.7 93 Example 32 344 2017 C24 H2j F3 Ne 02 483.2 6.8 100 Example 32 345 2018 F3 Ne 〇2 483.3 6.0 99 賨 Example 32

-353- 200526665 (349) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 346 2019 〇24 H26 Cl N7 〇3 S 528.1 1 4.4 96 Example 33 347 2020 C25 H2e Cl N7 〇3 s 542.1 1 4.3 100 Example 33 348 2021 C25 Hgg Cl N7 〇2 S 526.1 1 4.8 98 Example 33 349 2022 C25 H32 Νβ 〇2 449.2 6. 7 100 Example 32 350 2023 C26 H29 Cl Νβ 〇2 S 525 · 1 7. 3 98 Example 32 351 2024 C25 H30 Cl N7 〇2 s 528.1 8.8 98 Example 33 352 2025 C26 H29 Cl N © 〇2 S 525.2 7.2 94 Example 33 353 2026 C26 H30 Cl n7 o2 s 528.1 1 8.9 100 Example 32 354 2027 c25 H27 Cl Ne 〇3 S 527.2 5. 5 96 Example 33 355 2028 C2B H29 Cl N8 〇2 S 549.0 9.7 97 Example 32 356 2029 C25 H2 OCl F N6 O2 S 523.1 1 5.8 97 Example 32 357 2031 C24 H23 F Νβ 〇2 447.1 5.5 100 Example 32 358 2032 C25 H20 Cl F N6 02 S 523.1 1 6.3 98 Example 32 3S9 2033 C24 H21 Cl F N7 O2 S 526.1 7.8 94 Example 32 360 2034 C25 Hig Cl F2 Ne 02 S 541.0 6.7 96 Example 32 361 2036 C24 H20 Cl 〇 2 S 544.1 17. 6 94 Example 32 362 2040 c2, h22 ci2 n6 02 497.3 6.6 100 Example 33 363 2042 H2a F3 Nc 〇2 497.3 3 6.3 97 Example 33 364 2046 C2S H23 F3 N6 02 497.3 3 6.6 98 Example 33 365 2049 C25 H21 Cl f3 n7 o2 s 576.1 1 8.9 100 Example 32 386 2052 C26 H20 Cl F3 Ne 〇3 S 589.0 0 7. 6 98 Example 32 367 2053 c25 H21 Cl F3 N7 〇3 s 592.1 1 9.0 100 贲 Example 32 368 2054 C24 H24 F3 N7 〇3 516.2 8.0 100 Example 32 369 2056 CjB H20 Cl F3 Ne 〇3 S 589.0 7.7 98 Example 32 370 2058 C25 H21 Cl F3 N7 〇3 s 592.1 1 9. 1 100 Example 32

354- 200526665 (350) Example number Compound number Composition formula ES1 / MS m / e HPLC min Purity (%) Synthesis 371 2060 C2e H23 Cl N6 03 S 535.1 6.3 99 Example 32 372 2062 〇26 Hj3 Cl Νβ 〇3 S 535. 1 6.2 96 Example 32 373 2063 C25 Η24 Cl Ν7 〇3 S 538.1 7.7 91 賨 Example 32 374 2064 C, s Η26 Ne 〇3 459.1 5.3 100 Example 32 375 2065 C26 Η23 CI Ν6 〇3 S 535.1 6. 1 99 Example 32 376 2067 C25 Η24 CI Ν7 03 S 538. 1 7.7 91 Example 32 377 2068 C27 Η25 CI Νβ 〇4 S 565.1 1 5.8 89 Example 32 378 2069 C26 H2s Cl Ν7 〇4 S 568.1 7.0 63 Example 32 379 2070 C27 Η25 Cl Νβ 〇4 S 565.1 6.5 87 Example 32 380 2071 〇2β Η2β Cl Ν7 〇4 S 568.1 1 7.7 94 Example 32 381 2072 C28 H21 CI Νβ 04 S 549.1 54. 1 6.2 96 Example 32 382 2073 C2 Η22 CI Ν7 〇4 s 552.0 7.5 90 Example 32 383 2078 〇26 Η23 Cl 〇4 S2 583.0 5.6 78 Example 32 384 2080 〇2β Η27 Cl Νβ 〇2 S 551.0 5.8 95 Example 33 385 2081 C2A Η2〇CI ν7 02 S 506.1 4. 1 65 Example 33 386 2083 〇24 Η2 0 CI Ν7 〇2 S 506.1 1 4. 1 75 Example 32 387 2085 Η, β CI2 Ny 〇2 S 540.0 5.0 88 Example 32 388 2086 〇23 Η20 CI2 Νβ 〇2 S 543.0 6.9 100 Example 33 389 2087 〇23 H-J9 CI Νβ 〇3 S 495 · 6 5.6 90 Example 32 390 2089 〇23 His CI Νε 〇2 ^ 2 511.0 5.8 94 Example 32 391 2093 Cje Η23 〇Ι Ng 〇2 S 519. 1 6 · 5 98 Example 32 392 2094 〇26 Η23 Cl Nq 〇2 S 519.1 6. 5 98 Example 32 393 2095 C27 Η25 CI Νβ 〇3 s 549.1 1 6.4 100 Example 32 394 2096 〇27 H25 CI Νβ 〇3 S 549 1 6.4 94 贲 Example 32 39S 2097 C26 Η26 CI Ν7 03 S 552.1 7.9 94 Example 32

-355- 200526665 (351) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 396 2098 C26 H23 Cl F N7 02 S 540.1 8, 2 100 Example 32 397 2099 ◦25 Ηίβ Cl F3 Ne 〇2 S 558.9 9.6 96 Example 32 398 2100 〇23 H17 CI2 N7 〇2 S 526.0 6.0 93 Example 33 399 2101 C21 H-jg Cl N7 〇2 S2 497.9 6.4 85 Example 32 400 2102 〇2d Hjo Cl F2 N7 〇2 s 544.1 8. 1 93 賨 Example 33 401 2103 C25 H22 F4 〇2 515.3 6.7 97 Example 33 402 2105 C25 H22 0: 515.3 6.6 100 Example 33 403 2107 C30 H2B Νβ 〇2 505.4 7.0 80 Example 33 404 2109 C25 H21 Cl Νβ 〇2 S 505.1 1 6. 1 89 Example 33 405 2110 C18 H21 Ns 〇3 356.3 4.5 91 Example 28 406 2116 C20 H26 Ne 〇3 399.1 1 6.7 100 Example 28 407 2119 C23 H32 Νβ 〇s 441.2 2 8,1 86 Example 28 408 2120 C «is H22 N4 〇4 371.0 0 7.4 33 Example 70 409 2122 〇23 H2e Ne 〇4 451.0 7.7 41 Example 70 410 2127 C18 H10 Cl Nb 03 S 462.9 8.6 98 Example 28 411 2141 〇2β H28 N4 O4 461.0 Π.5 99 Example 10 412 2142 Cai Hst N5 O4 538.0 9.3 99 贲 Example 28 413 2143 〇s〇H32 Νβ 〇4 541.1 1 11.4 70 Example 28 414 2146 C22 H22 Cl N5 O3 S 472.1 1 6.8 99 賨 Example 35 415 2147 C25 H20 Cl N5 O3 S 506.1 7.1 98 Example 35 416 2148 C22 H22 Cl N5 〇a S 472.1 6.8 99 Example 35 417 2158 C20 H23 N5 〇2 366.4 4. 7 100 Example 49 418 2161 C24 H29 N5 〇2 420.3 7. 1 93 贲 Example 63 419 2162 〇23 H3〇Ng 〇2 423.3 7.8 100 Example 63 420 2164 C24 Hgg Ne 〇2 S 465.3 8.6 100 Example 53

-356- 200526665 (352) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis method 421 2165 〇29 H33 N5 〇4 516.4 7.5 99 Example 53 422 2165 〇25 H27 N5 〇3 446.2 7.3 98.9 Example 53 423 2166 C2B Ne O4 519.3 8.1 100 Example 53 424 2170 C24 H28 Νθ 〇 03 44. 3 8 · 3 100 Example 53 425 2175 C30 Hs ·) N5 O3 510.3 7'6 88 Example 63 426 2176 〇29 H32 Νβ 〇3 513.4 8.2 100 Example 63 427 2183 〇24 Η24 F Ν5 〇2 S 466.3 6.2 98 Example 53 428 2184 〇23 Η25 ΡΝβ 〇2 S 469.3 7.6 100 Example 53 429 2185 〇2B Η30 F Ν5 〇4 520.3 6. 1 99 Example 53 430 2186 c27 Η31 F Ne 0.523.3 7.7 98 Example 53 431 2187 C24 Η24 F Ν5 O3 450.3 5.9 98 Example 53 432 2188 C23 H25 F Νε 〇3 453.3 7.3 100 Example 53 433 2202 C21 Hz5 Ng 〇2 380.4 5.3 100 Example 49 434 2209 C21 H-ib N5 〇2 374, 3 5. 1 100 Example 49 435 2210 C24 H22 Γ &quot; N5 〇2 432.2 7.0 93 Example 63 436 2211 C23 H23 F Ng 〇 2 435.3 7.8 100 Example 63 437 2212 C25 H22 f &quot; 3 Ns 〇2 482.3 7.2 79 Example 63 438 2224 〇25 H22 F3 Ns 〇3 498.3 7. 5 99 Example 63 439 2240 c25 Hu F Ns 02 446. 3 7.0 96 Example 63 440 2241 〇24 H25 F Ne 〇2 449.3 7.6 100 Example 63 441 2265 Czs Hsn N5 〇2 434.3 7.5 98 Example 63 442 2266 C2 &lt; H32 N6 〇2 437.4 8.3 100 Example 63 443 2267 〇28 H29 N5 〇2 S 476.3 7.5 98 Example 53 444 2268 C25 H30 Ne 〇2 S 479.3 9,1 100 Example 53 445 2270 C29 H31 N5 〇A 514.0 8.2 100 贲 Example 53 -357- 200526665 (353) Example number Compound number Composition ESI / MS m / e HPLC min purity (%) synthetic method 446 2271 〇28 H29 N5 〇3 460.3 7.4 93 Example 53 447 2272 〇25 Νβ 〇3 463.3 8.8 100 Example 53 448 2275 226 H33 N5 〇2 448.3 8.2 83 Example 63 449 2277 C2S H34 Νε 〇2 45L4 9.0 100 Example 63 450 2281 〇27 H31 Ns 〇2 S 490.4 7. 7 100 Example 53 451 2282 〇2β Η32 Νβ 〇2 S 493.3 9. 8 100 Example 53 452 2287 ^ 31 Η37 Ns O4 544.5 7.7 100 賨 Example 53 453 2288 〇29 Ηββ Νβ 〇4 533.3 9.0 100 Example 53 454 2288 ^ 30 H3B Νβ 〇4 547.4 9.4 99 Example 53 455 2290 C27 H31 N5 〇3 474.5 5 7.5 100 Example 53 456 2291 〇2Β H32 Νβ 〇3 477.4 9.5 100 贲 Example 53 457 2296 〇25 Η25 Ns 〇2 428.3 5.9 96 贲 Example 63 458 2298 〇2A Η22 F Ν5 〇2 432.3 5.8 95 Example 63 459 2299 C * jg Η03 Ν5 〇2 354.4 4.6 100 Example 49 460 2300 Cie His Ns 〇4 370.3 2.2 100 Example 49 461 2301 〇Τ8 Η21 Νδ 〇3 356.4 4 2.5 100 Example 49 462 2305 C25 Η24 F Ns 〇2 446. 3 5.9 98 Example 63 463 2311 ^ 26 Η24 Ns 〇2 496.3 7.1 98 Example 63 464 2325 〇26 Η24 F3 Ν5 Ο3 512.3 7.3 98 Example 63 465 2329 C2e Η27 Ns 〇2 442.4 6.3 98 Example 63 466 2336 〇27 Η25 Νδ 〇2 S 484.3 7. 3 98 Example 53 467 2337 〇2e Η2β Νβ 〇2 S 487.3 8.7 100 Example 53 468 2340 C24 Η26 Νβ 〇2 431.4 7.4 100 Example 53 469 2341 〇26 Ηζ7 Ns 〇2 442.5 6.4 6. 6 100 Example 53 470 2342 Cai Η2〇Ns 〇 2 504.4 7. 7 7.9 100 Example 53

-358- 200526665 (354) Example number Compound number Composition formula ESI / MS m / e HPLC min Purity (%) Synthesis 471 2343 〇32 ^ 29 ^ 5 〇3 532.4 8.0 100 Example 53 472 2344 〇31 H3T Ns 〇4 538.5 6.9 100 Example 53 473 2347 〇27 Η25 Ns 〇3 468.3 7. 1 98 Example 53 474 2348 〇26 H26 Νε 〇3 471.3 8.4 100 Example 53 475 2350 〇23 Η23 Ν5 〇3 418.3 5.1 · 1 98 Example 63 476 2356 C2e H27 N5 〇2 442-2 7.1 87 Example 63 477 2357 C25 H28 Ne 〇2 445.3 7.8 100 Example 63 478 2446 C17 H1t Cl N4 0 323 · 2 4-5 100 Example 53 479 2448 Ci7 Hi2 〇2 305.3 2. 5 100 Example 53 480 2452 Ci0 H-14 N4 〇2 319.3 4.2 100 Example 53 481 2459 C-J8 H-14 〇2 319.3 2.9 100 Example 53 482 2469 cne h13n6o 292.2 2.9 100 Example 53 483 2471 C15 H10 N4 0 s 295.3 3.2 100 Example 53 484 2481 Ctb H10 N4 〇2 279.3 2.5 100 Example 53 485 2484 Cm Hn〇Cl2 N4 0 357.0 5.5 100 Example 53 486 2486 C19 Hig 〇3 349.2 4.1 100 Example 53 487 2490 C * je His N5 O3 S 382.3 4.0 100 Example 53 488 2492 Cie H12 〇3 333.3 2.7 100 Example 53 489 2495 Cie H * j3 N5 〇328.3 5,1 100 Example 53 490 2500 H22 N4 〇3 439.0 7.5 94 Example 53 491 1562 C24 H27 N5 〇2 418.5 5.7 99贲 Example 36 492 1895 C25 H28 Ne 〇2 445.5 5.7 99 Example 36 493 1875 C21 Ht〇Fe N5 〇2 488,3 6.5 99 Example 36 494 2S14 C30 H3 ·, N5 〇3 510.5 6.6 99 Example 36- 359-200526665 (355) Example 495 Determination of HNR (400MHz, DMSO-d6 or CDCls) of the compound of the present invention. Table 3 shows the data of its chemical shift ((5: ppm)) and coupling constant (J = H2). The compound numbers in the table represent the compound numbers of Table 1 listed in the above-mentioned preferred specific examples. Example numbers of the corresponding compounds are shown. Example number Compound number NMR data δ (ppm) Solvent 72 27 1.2B-1.44 (mt 2H), 1.76 (m, 2H), 2.76 (m, 1H), 2.84 -3.01 (m, 2H), 3.15 (m, 1H), 3.6B (m, 1H) f 3.87 (d, J = 12.96, 1H), 4.39 (d, J = 11.96, 1H), 4.62 (m, 2H ), 7.52 (m, 2H), 7.63 (m, 1H), 7.79 (dd, J = 5.38, J = 8.06, 1H), 7.97 (mf 3H), 8.24 (s, 1H), 8.59 (d, J = 5.36, 1H), 8.78 (d, J = 8.32, 1H), 9.37 (s, 1H), 12.24 (brs, 1H) · DMSO- d6 73 29 0.00 (m, 2H), 0.25 (m, 2H) t 2.28 (m, 1H), 2.37 (t, J = 6.70 &gt; 2H), 4.34 (t, J ^ 6.60T 2H), 7.58 (dd, J = 5.50, J = 7.94, 1H). 7.69 (d, J = 3.92t 1H), 7.73 (s, 1H), 7.86 (s, 1H) t 8.35 (d, J = 5.36, 1H), 8.58 (d, J = 8.28, 1H), 9.14 (s, 1H), 12.02 ( brs, 1H). DMSO- d6 75 80 3.96 (m, 2H), 4.49 (m, 1H), 4.88 (m, 1H), 7.11 (m, 1H), 7.73-7.79 (m, 2H) t 7.83 (m , 1H) t 7.8B (brs, 1H), 8.03 (t J-7.7, 1H), 8.18 (d, J = 8.5, 1H), 8.64 (s, 1H), 10.00 (brs, 1H), 12.29 (brs, 1H) .DMSO- d6 202 1106 1.44 (brs, 2H), 1.62 (brs, 4H) , 3.45 (m, 4H), 5.39 (s, 2H), 7.81 (dd, J = 5.48, J = 8.16, 1H), 7.98 (s, 1H), 8.09 (s, 1H), 8.60 (d, J = 5.40, 1H), 8.80 (d, J = 8.04, 1H), 9.39 (s, 1H), 12.18 (brs, 1H). DMSO- d6 206 1161 5.36 (s, 2H), 7.05 (m, 1H), 7.31 (tt J = 7.56, 2H), 7.58 (d, J = 7.56, 2H), 7.81 (dd, J = 5.24, J = 8.16, 1H), 8.00 (s, 1H), 8.18 (s, 1H), 8.61 (d, J = 5.36, 1H), 8.80 (d, J = 8.04 (1H) t 9.41 (s, 1H) t 10.37 (s, 1H), 12.26 (brs, 1H). DMSO- d6 208 1170 1.19-1.23 (m, 3H), 4.13-4.20 (mt 2H), 5.30 (s, 2H), 7.79 (m, 1H), 8.00 (d, J = 3.92, 1H), 8.15 (d, J = 4.16, 1H), 8.60 (m, 1H), 8.76 (dr J = B.07t 1H), 9.37 (s, 1H), 12.28 (brs, 1H). DMSO- d6 209 1174 4.06 (s, 3H), 7.84 (ddt J = 5.36 , J = 8.03, 1H), 7.96 (s, 1H), 8.16 (s, 1H), 8.61 (d, J = 5.12t 1H), 8.84 (d, J = 7.75, 1H), 9.39 (s, 1H) , 12.21 (brs, 1H). DMSO- d6 212 1179 5.67 (s, 2H), 7.13-7.36 (Γη, 5H), 7.B0 (dd, J = 5.35, J = 8.03, 1H), B.00 ( s, 1H), 8.36 (s, 1H), 8.60 (d, J = 5.36, 1H), 8.83 (d, &gt; 8.07, 1H), 9.40 (s, 1H), 12,29 (brs, 1H). DMSO- d6

Example 496 Measurement of Enzyme Activity Inhibiting GSK-3 In a test compound (5 μΐ) with 5% dimethasone as a solvent, -360- 200526665 (356) was added with 25 μΐ of phosphate monohepatose synthase peptide -2 matrix solution [contains 6 μM phosphate monoglycosylase-2, 20 μM ATP, 16 mM MOPS buffer (pH 7.0), 0.2 mM EDTA, 20 mM magnesium acetate, 0.1 MCi [r-

33P] ATP (activity ratio: about 110TBq / mmol)], and then add GSK-3 stone buffer (20 μΐ) [containing 10mU recombinant human GSK-3 / 5, 20mM MOPS buffer (pH7.0), 1 mM EDTA, 0.1% polyoxyethylene lauryl ether (23 lauryl ether; Brij 35), 5% glycerol, 0.1% / 3-hydrothiothioethanol], and the reaction was started. After reacting at room temperature for 20 minutes, an equal volume of 200 mM phosphoric acid solution was added to terminate the reaction. The reaction product (90 μΐ) was adsorbed on a multi-screen pH plate (manipur company product) and washed with 100 mM phosphoric acid solution. After the pH plate was dried, 30 μΐ of Micro Scint-0 (manufactured by Packard BioScience) was added, and the CPM was measured with a flash meter to investigate the inhibitory activity. Structure of Hepatic Phosphate Synthase Peptide-2 A rg-H is-Ser-Ser-P r 〇-H is-G1 η-Ser (P) -Glu-Asp-Glu-Glu-G1 u 〇The results of measuring the GSK-3 enzyme inhibitory activity (IC5G 値) of the compound of the present invention by the above method, and the compound numbers are 263, 280, 287, 297, 615, 617, 618, 627, 629, 641, 668, 760, 7 8 5, 10 14 '1183' 1206, 1216, 1217, 1228, 1 23 7 '1 243' 1 25 0, 1 25 7, 127 1, 1286 ^ 1287, 1288, 1 293, 1 296, 1 3 74, 1 3 99, 1 405, 1415, 1423, 1427, 1 430, 1 44 5, 1 494, 1514, 1 549, 1553, 1566, 1589, 1 600 '1 647, 1 654, 1 660 ^ 1661, 1679, 1693, 1695, 1715, 1721, 1 890, -361-200526665 (357) 1 900, 2007, 2008, 2010, 2011, 2012, 2013, 20 14, 2015, 2017 '2022, 2026, 203 1, 2032, 203 3 &gt; 2034 &gt; 2 03 6, 2040, 2042 '2046, 2049, 205 3, 2054, 2 05 8, 2, 062, 2 063 ^ 2064 ^ 2065' 2067 &gt; 2068 '2069 ^ 2070' 2 07 1, 2072, 2073 &gt; 2078, 2080, 2083, 208 5, 2086 &gt; 2095, 2097, 2098, 2102, 2103, 2 105 '2107, 22 12, 2 224, 23 11 Compounds confirmed 1 (: 5 () &lt; 2 〇11] ^。 Inhibitory activity. Also, the compound number is 40, 217, 219, 230, 245, 269, 288, 303, 595, 596, 601, 602 '616, 626, 628, 634, 646, 657, 659 , 664, 667 &gt; 668, 673, 689, 694, 696, 723, 733, 734, 741, 768, 770 '776, 793, 795, 801, 802, 803, 804, 805, 806, 807, 809, 809, 810, 812, 915, 1182 '1186, 1 2 3 6, 1, 260' 1 277, 1 27 8, 1 2 8 2 '1 284, 1 3 3 5, 1 3 3 7 ^ 1 3 3 8 ^ 1341, 1 3 64, 14 13, 1 482, 1 486, 1 490, 15 19, 1 5 2 0, 1 5 3 3 '1 5 54, 1 5 5 8 ^ 1 62 3, 1 673, 1 6 8 2, 169 1, 1 696 '1 700, 1719, 1 73 9, 1, 74 8, 1751, 1 7 5 3, 1 7 5 8, 1 7 7 8, 1 806, 1 808, 1 846, 1 849, 1 85 2, 1 8 5 5, 1 8 6 5, 1 8 6 8, 1 8 8 5 '1 894, 1 899 , 2004, 2005 '2006, 2016, 2018, 2019' 2020, 202 1, 2024 '2025, 202 7 &gt; 2 029, 2052 &gt; 2056, 2060, 208 1, 208 7' 2089, 2094, 2099, 2100 ' 2101, 2146 '2147, 2148' 2161, 2 175, 2 183, 2184, 2210, 22 1 1, 2240, 224 1, 2265, 2266, 2275, 2296, 2298, 2305, 2325, 2329, 2331 '2 3 3 Compounds with 2, 2 3 3 6, 2, 3 3 7, 7, 2341, 2342, 2347, 234 8, 23 50, -362- 200526665 (358) 2448, 248 6, 2492 were confirmed to have inhibitory activity of 20nM &lt; IC5G &lt; 100nM . * In addition, the compound numbers are 81, 84, 254, 257, 320, 321, 330, 348, 361, 492, 504, 536, 550, 605, 678, 684, 702, 704, 709, 713, 718, 724, 729, 808, 811, 917, 918, 946, 1001, 1002, 1007, 1008, 1178, 1181, 1184 &gt; 1185, 1258, 1259, 1261 '1262, 1297, 1331' 1333, 1 3 3 4, 15 11 , 1 522, 1 5 3 0, 1 5 3 5, 1 697, 1 804, 1805 1 823, 1 8 3 3 ^ 1 843, 1 8 60, 1861, 1891, 1913, 1915 2 003, 2023, 202 8 '2093' 2096, 2109, 2 116, 2 158 &gt; 2162, 2 164 '2 165, 2166' 2 170 '2176' 2186 '2 187 2 188, 2202, 2209, 2264, 2267, 2268, 2269' 2270 \ 22 7 1, 22 72, 2277, 228 1, 2282 '228 8, 2290, 229 1 X 2292' 2299 '23 00, 2340, 2344, 2345, 23 5 6, 23 5 7 2445, 2446, 2452, 2459' The compounds of 2469, 247 1, 248 1, 2484 2490, and 2495 were confirmed to have an inhibitory activity of 100 nM &lt; IC5G &lt; l OOnM. The compound numbers represent the compound numbers in Table 1 listed in the above-mentioned preferred specific examples. From the above, it is understood that the pyrrolopyrimidone derivative of the present invention shows a strong inhibitory activity against GSK-3. Therefore, the compounds of the present invention can be used clinically by providing GSK-3 activity-inhibiting substances for the prevention and / or treatment of various diseases related to GSK-3. -363- 200526665 (359) Example 49 7 Manufacturing of lozenges Each lozenge is manufactured into the following composition. Compound (Example 1) 50 mg lactose 2 30 mg potato starch 80 mg polyvinylpyrrolidone 1 1 mg magnesium stearate 5 mg mixed with the compound of the present invention (the compound of Example 1), lactose and potato starch, and then 20 with polyvinylpyrrolidone The% ethanol solution was evenly moistened, sieved through a 20-mesh sieve, dried at 45 ° C, and then sieved through a 15-mesh sieve. The obtained granules were mixed with magnesium stearate and compressed into a tablet. Reference example 15 Ν- {2- [4 · chloro-6- (3-chloro (2-thienyl) -7-iodopyridine [3,2-d] pyrimidin-5-yl) ethyl] · 2 Of 2,2,2-trifluoroacetamidamine

Contains N- {2_ [6- (3-chloro (2-thienyl) -7-iodo-4-oxy (3-hydropyrrole [3,2-d] pyrimidin-5-yl)) ethyl] • A solution of 2,2,2-trifluoroacetamidamine (333 mg) in phosphonium chloride (3.0 ml) was stirred at 110 ° C for 2 hours. The reaction mixture was cooled to room temperature, and excess phosphorous chloride -364-200526665 (360) was distilled off under reduced pressure. The residue was dried in vacuo to give the title compound as a brown oil. Provides the use of subsequent reactions without purification. ESI / MS data for the following * $ &amp; ESI / MS m / e: 5 3 5.2 (M + + H, Ci4H8C12F3IN4OS) Reference Example 16 &gt; ^ {2- [7-Bromo-4-chloro-6- (3-chloro (2-thienyl) -pyrrole Synthesis of 骈 [3,2-d] pyrimidin-5-yl) ethyl] -2,2,2-trifluoroacetamidamine

In the same manner as in Reference Example 15, N- {2- [7-bromo-6- (3-chloro (2-thienyl)) · oxy (3-hydropyrrolo [3 '2-d] pyrimidine-5 -Yl)] ethyl 2,2,2-trifluoroacetamidamine to give a purified product of the title compound. The ESI / MS data of this compound are shown below. ESI / MS m / e: 489.0 (M + + H, C14H8BrCl2F3N4〇S) Example 17 Ν- {2- [4 '7 · Dichloro-6- (3-chloro (2-thienyl) pyrrolo [3] Synthesis of 2,2-d] pyrimidin-5-yl) ethyl] -2,2,2-trifluoroacetamidamine-365- 200526665 (361)

Following the same method as in Example 15, N- {2- [7-chloro-6- (3-chloro (2-thienyl))-4-oxy (3-hydropyrrolo [3,2-d] pyrimidine) was used. (-5-yl)] ethyl} -2,2,2-trifluoroacetamidamine to obtain a purified product of the title compound. The ESI / MS data of this compound are shown below. ESI / MS m / e: 443.4 (M + + H »C ι 4 Η 8 C13 F 4N4 0 S) [Industrial application field] In the present invention, the pyrrolopyrimidone derivative represented by the above formula (I) 'and Its medically acceptable salt has a GSK-3 inhibitory effect and can provide the use of active ingredients of pharmaceuticals. That is, the medicament containing the compound of the present invention as an active ingredient can provide diabetes, diabetic dysplasia, AIDS, neurodegenerative disease, dryness, traumatic brain injury, hair loss, inflammatory diseases, cancer, immunity Uses for the treatment or prevention of inequalities related to GSK-3. -366-

Claims (1)

200526665 (1) 10. Scope of patent application 1. A compound represented by the following formula (I) or a medically acceptable salt thereof, a2-g1-a3-a4-g2 (I) In formula (I), A1 represents a single bond or a bivalent acyclic formula in which a nitrogen atom bonded to A1 and A2 are bonded at the same or different carbon atoms. Aliphatic hydrocarbon group, A2 shows a single bond, or a group that combines A1 and G1 in the form below, A] -C (= 0) -G1, A] -C (= 0) -O-G1, A] -C (= 0) -NR ^ -G1, A] -C (= S) -NR102-G], A 丨 -C (= NR103) -G1, A ^ O-G1, A1-0-C (= 0) -G1 'A ^ NR104 ^ 1 ^ A] -NR105-C (= 0) -G1, A ^ NR106 ^ (= 0) 2-G1' A ^ NR ^ -C (= 0) -0-G], A ^ NR ^ LC (= 0) -NRio'G1, -367- 200526665 (2) A ^ NR1 10-C (= S), A ^ NR111 ^ (= S) -NRii2 A ^ S-G1, A, S (= 0) -G1, A -S (= 0) 2-G], A1 "(= 0) 2-NR1 13-Gi, A ^ CR1 14 = CH-G1 'A ^ CR1, 5 = CF- G1 ^ A ^ CHsCR1 “-G1, or A ^ CFsCR1】 7-G1 〇G1 is a single bond, or C3 ~ ClG alicyclic hydrocarbon group which can be substituted, and c6 ~ c14 aromatic hydrocarbon which can be substituted, The k-like group may have a divalent group obtained by removing two hydrogen atoms from any one of the heterocyclic compounds grouped by an oxygen atom, a nitrogen atom, and a sulfur atom in the substituted ring. A3 represents a single bond. Or combine G1 and A4 on the same or different carbon atoms A C ^ Cio divalent acyclic aliphatic hydrocarbon group which may be substituted, A4 represents a single bond, or a group that combines a3 and G2 in the following form, A3-C (= 〇) -G2, A, C (= 〇) -〇-G2, A, C (= 〇) -NR121-G2, A3-C (= S) _NRI22-G2, A3-C (= NR123) -G2 'A-〇-G 2, A3-〇 -C (= 〇) -G2, -368- 200526665 (3) a3-nr124-g2 A3-NR125-C (= 0) -G2, · a3-nrI26-s (= 0) 2-g2, A3-NR127 -C (= 0) -O-G2, A3-NR128-C (= 0) -NR129-G2, A3-NR 13 0-C (= S)-G 2 'A3-NR131-C (= S)- NR132-G2, a3-s-g2, A3-S (= 0) -G2, A ^ -S (= 0) 'A3-S (= 0) 2-NR133-G2, or A3-S (= 0) 2-O-G2, G2 shows hydrogen atom Acyclic aliphatic hydrocarbon group that can be substituted, C3 ~ C that can be substituted] G alicyclic hydrocarbon group, C6 to C14 aromatic hydrocarbon group that can be substituted, or 1 to 4 options in the ring that can be substituted A heterocyclic group consisting of an oxygen atom, a nitrogen atom 'and a sulfur atom, A5 shows a single bond or · Νί1201-, R2 shows a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. The acyclic aliphatic hydrocarbon group of CrCM can be substituted, and the c3 ~ r alicyclic hydrocarbon group can be substituted. A C6 ~ CM aromatic hydrocarbon group that can be substituted, or a heterocyclic group with 1 to 4 groups selected from oxygen, nitrogen and sulfur atoms in the ring that can be substituted, A6 shows a single bond, or The carbon atom of the pyrrole ring that binds R3 and a6 is a group bonded in the following form, -369- 200526665 (4) 113-1 ^ 113 () 1- [] ratio ring, R3-C (= 0)-[ ] Pyrrole ring, R3-NR3G2-C (= 〇), Pyrrole ring, R3_NR3t) 3_C) -D Pyrrole ring, R3-NR3G4-C (= 〇) _NR 3 0 5 -Pyrrole ring, R3-C (= 0) -NR3G6-d ratio ring, R3-NR307-CH = ND ratio ring, R3-C (= 0) -〇-pyrrole ring, R3-0-C (= 〇) -D ratio ring, R3-0-pyrrole ring, R3-S-pyrrole ring, r3-s (= o) · pyrrole ring, R3-S (= 0) 2-pyrrole Ring, R3-CR3Q8 = CR3 () 9-pyrrole ring, R3-C tri-C-pyrrole ring, or r3-s (= 0) 2-C tri-c-pyrrole ring R3 shows hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, nitro group, but C ^ Cio substituted acyclic saturated aliphatic hydrocarbon group, C3 ~ c8 alicyclic hydrocarbon group which can be substituted, c6 ~ c14 aromatic hydrocarbon group which can be substituted, 1 to 4 options in the substituted ring A heterocyclic group formed from an oxygen atom, a nitrogen atom, and a sulfur atom, and the portion shown by A6_R3 may be A6 in the form of R3-CR3〇8 = CR309-pyrrole ring or r3-c ^ c-pyrrole ring. A group bonded to the carbon atom of the pyrrole ring, and R3 may be a trimethylsilyl group, a methylamino group, a C2 to c7 amidino group-370-200526665 (5), a carboxyl group, a C2 to C7 alkoxycarbonyl group, Amine formamidine group, which can be substituted (: 2 ~ 07 alkylamine formamidine group, or a combination of cyano groups, where R1 () 1-R117, R121-R133, R2 () 1, and R3G1-R3G9 are Each independently shows a hydrogen atom or C] ~ C4 acyclic aliphatic hydrocarbon group, but when A1 and A3 are both acyclic aliphatic hydrocarbons, at least either of A2 or G1 will not be a single bond. 2. If applying for a patent Compound of Scope 1 or its medical Permissible salts, wherein A1 in formula (I) is a divalent acyclic alicyclic hydrocarbon group. 3. For example, the compound of the scope of patent application No. 1 or a medically acceptable salt thereof, wherein formula (I ) In A2 is-(CH2) 2 · or-(CH2) 3-. 4. If the compound in the scope of patent application item 2 or item 3 is a medically tolerable salt 'wherein formula (I) In A2, it is not a single bond. 5. If the compound in the scope of the patent application is the second or third compound, its medically acceptable salt, where in formula (1), A2 is -C (= 0) · , _C (= 0) -〇-, -C (= 0) -NH ·, -C (= 0) -NMe-, -NH-, -NH-C (= 〇)-, -NH-C (= 0) · 0-, -NH-C (= 〇) -NH-, -NH-C (= 〇) -NMe-, or-NH-C (= S)-6. If the scope of patent application is the second The salt of the compound of item 3 or item 3 which is medically acceptable, wherein A2 in formula (1) is -C (= 0) -NH ... -NH-, -NH-C (= 0)-, -NH -C (= 0) -〇-, or -NH-C (= 0) -NH-. 7. If the compound in the scope of patent application 1 is medically tolerable -371-200526665 (6), Wherein A1 and A2 in formula (I) each represent a single bond. The compound of any one of claims 1 to 6 or a medically acceptable salt thereof, wherein the combination of G1, A3, A4, and G2 is any one of the combinations 1 to 10 in the following table. _ Combination G1 A3 A4 G2 1 Single bond other than single bond single bond hydrogen atom 2 Single bond other than single bond single bond hydrogen atom 3 Single bond other than single bond single bond other than single hydrogen atom 4 Single bond single bond Bases other than single-bonded hydrogen atom 5 Bases other than single-bond single-bond other than single-bond base Other than hydrogen atom 6 single-bond single-bond other than single-bond base other than hydrogen atom 7 other than single-bond Radicals other than single bonds, radicals other than single hydrogen atoms, radicals other than single bonds, radicals other than single bonds, radicals other than single bonds, radicals other than hydrogen atoms, radicals other than single bonds, radicals other than single bonds, radicals other than single bonds Basic hydrogen atom 10 Single bond Single bond Single bond hydrogen atom 9. The compound according to any one of claims 1 to 7 or a medically acceptable salt thereof, wherein G1 in formula (I) is shown For groups other than single bonds, A3 and A4 are single bonds, and G2 is a hydrogen atom. 10. If the compound of any one of items 1 to 7 of the scope of patent application or a medically acceptable salt thereof, wherein G1 and A4 in formula (I) are shown as single bonds, and A3 is shown as other than single bonds G2 is a hydrogen atom. 11. If the compound of any one of claims 1 to 7 or a medically acceptable salt thereof, G1 is a base other than a single bond, A3 and A4 are single bonds, and G2 is a single bond. A radical other than a hydrogen atom. -372- 200526665 (7) 12. If the compound of any one of claims 1 to 7 or a medically acceptable salt thereof, wherein G1 and A4 in the formula (I) are single bonds, A3 is a group other than a single bond, and G2 is a group other than a hydrogen atom. 1 · If the compound No. 12 of the scope of patent application or a medically acceptable salt thereof, wherein A3 in the formula (I) is an alkenyl group. 14. If the compound of any one of items 1 to 7 of the scope of patent application or a medically acceptable salt thereof, wherein G1 and A4 in formula (I) are groups other than a single bond, and A3 is a single Bond, G2 is a group other than a hydrogen atom. 15. The compound or a medically acceptable salt thereof according to item 14 of the scope of patent application, wherein A4 is -C (= 0)-, _C (= 〇) -NH-, -0, or -NH- C (= 0)-. 16 · If the compound of any one of items 1 to 7 of the scope of patent application or a medically acceptable salt thereof, wherein G1 in formula (I) represents a single bond, and A3 and A4 are other than a single bond. G2 is a group other than a hydrogen atom. 1 7. If the compound of any one of items 1 to 7 of the scope of patent application or a medically acceptable salt thereof, wherein G1 and A3 in formula (I) are groups other than a single bond, and A4 is a single Bond, G2 is a group other than a hydrogen atom. 18. The compound of claim 17 or a medically acceptable salt thereof, wherein A3 in the formula (I) is an alkenyl group represented by the formula. 19. If the compound of any one of claims 1 to 7 of the scope of patent application or a medically acceptable salt thereof 'wherein G1, A3 and A4 in formula (I) are groups other than a single bond, G2 is Shows groups other than hydrogen atoms. 2 0. If the compound in the scope of patent application No. 19 or a medically acceptable salt thereof 'wherein A4 in formula (I) is not -0 &quot; *. -373- 200526665 (8) 21. If the compound of any one of items 1 to 7 of the scope of patent application or a medically acceptable salt thereof 'wherein G1, G3 and A4 in formula (1) are shown For a group other than a bond, G2 is a hydrogen atom. 2 2 · If any of the items 1 to 7 in the scope of the patent application or a medically acceptable salt thereof, wherein G1, A3 and a4 in formula (I) are not single bonds, G2 is not Ammonia atom. 23. If the compound in the scope of patent application item 3 or a medically acceptable salt thereof, wherein A2 in formula (1) is _NH_ (C = 〇), or · νη_ (C = 0) -ΝΗ-, G1 is a single bond, and A3 is a bivalent acyclic alicyclic hydrocarbon group showing Ci to C1G. 24. A compound or a medically acceptable salt thereof according to item 3 of the scope of patent application, wherein A2 in formula (1) is -NH_ (C = 〇) ... -NH- (〇0) -NH-, · ΝΗ-, or -C (= 0) -NH-, G1 is a group other than a single bond. 2 5 · If the compound of the second or third item of the scope of patent application or a medically acceptable salt thereof, wherein A2 in formula (1) represents a single bond and G1 represents a heterocyclic group that can be substituted, but When the heterocyclic group of G1 is a monocyclic ring of five to six members, the monocyclic heterocyclic group of five or six members is substituted or the A3-G2 part is other than a hydrogen atom. 2 6 · If the compound of any one of the 4th or 6th in the scope of patent application or a medically acceptable salt thereof, wherein in the formula (I), G1 is an aromatic hydrocarbon group which may be substituted and may be substituted C7 ~ C1G alicyclic hydrocarbon group, or heterocyclic group which may be substituted, but when the aromatic hydrocarbon group of G1 is phenyl, or when the heterocyclic group of G1 is a single ring of five or six members, the benzene of G1 Or five to six-membered ring mono-374-200526665 (9) Ring heterocyclyl is substituted or the A3-G2 part is other than hydrogen atom. 2 7. If the compound of any one of items 4 or 6 of the scope of patent application or a medically acceptable salt thereof, wherein in formula (I), G1 and A4 are single bonds, and A3 may be substituted For non-cyclic alicyclic hydrocarbon groups, G2 is an alicyclic hydrocarbon group which may be substituted with C5 to C1G, an aromatic hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted. 2 8. If the compound of any one of items 4 to 6 of the scope of patent application or a medically acceptable salt thereof, wherein ⑴ in formula (I) represents a single bond, and A3 represents a non-substituted Cyclic aliphatic hydrocarbon group, A4 is shown as -C (= 0)-, -C (= 〇) -NR121-, -C (= S) -NR122-, -C (= NR123) = &gt; -OC (= 〇)-&gt; -NR125-C (= 0)-'-NR126-S (= 0) 2-, -NR127-C (= 〇) = 〇-, -NR128-C (= 0) -NR] 29 -, -NR130-C (= S)-, -NR13] -C (= S) -NR132-, -S-, -S (= 0)-, -S (= 0) 2 ·, -S (= 0) 2-NR] 33-, or-S (= 0) 2-〇-. 2 9 · If the compound of any one of items 1 to 28 of the scope of patent application or a medically acceptable salt thereof, wherein A5 in formula (I) is a single bond. The compound according to item 29, or a medically acceptable salt thereof, wherein R2 in the formula (I) is an optionally substituted 2Cl ~ C1 () acyclic aliphatic hydrocarbon group, and a substituted C3 ~ C8 alicyclic ring. Formula nicotinyl, CfC! 4 aromatic hydrocarbon group which may be substituted, or heterocyclic group which may be substituted. 3 1 · If the compound in the scope of patent application No. 29 or its medically acceptable salt 'wherein R2 in formula (I) represents C] ~ C] 〇 acyclic aliphatic hydrocarbon group, (: 3 ~ C8 lipid Cyclic hydrocarbon group may be substituted phenyl, or substituted ring -375- 200526665 (10) A heterocyclic group having 1 to 2 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. 3 2. If the compound No. 29 of the scope of patent application or a salt thereof which can be medically used is' wherein R2 in formula (I) is cyclopropyl, cyclobutyl, cyclopropylmethyl, methyl, Ethyl, vinyl, isopropyl, isobutyl, or methyl-1-propenyl. 3 3 · If the compound of the scope of patent application No. 29 or its medically acceptable salt, wherein the formula ( I) R2 is a thiophene substituted by any one or plural of Cl ~ C4 alkyl, Cl ~ C4 alkoxy, C2 ~ C: 4 fluorenyl, hydroxyl, carboxyl, alkoxycarbonyl, fluorine atom or chlorine atom Group, D [t-ansyl group, sulfanyl group, D-pyrrolyl group, pyrazolyl group or phenyl group. 34. A compound according to any one of claims i to 33 in the scope of patent application or its medically acceptable A salt, wherein in formula (i)? Is a single bond 〇 5 5 · If the compound in the scope of patent application No. 34 or a medically acceptable salt thereof, wherein R3 in formula (I) is shown may be substituted C6 ~ C μ aromatic hydrocarbon group or heterocyclic group which may be substituted. 36. For example, the compound of the scope of application for the patent No. 34 or a medically acceptable salt thereof, wherein R3 in formula (I) is Or a thienyl, pyridyl, furyl, pyrrolyl, pyrazolyl, or phenyl group substituted by a Cl to C4 alkyl group. 37. For example, the compound in the scope of claim 34 or its medical use may be Permissible salts, in which R3 in formula (I) is pyridyl or 1-hydroxypyridyl, or hydrazone, or -376- 200526665 (11) N which may be substituted by a Cl ~ C4 alkyl group or a halogen atom. -Methylpyrazolyl. 38. The compound or a medically acceptable salt thereof according to item 29 of the scope of patent application, wherein A6 in formula (I) is a single bond. Compound or a medically acceptable salt thereof, wherein in formula (1), a single bond is shown, and R3 is a Ci ~ 0 alkyl group or a A pyridyl or hydroxypyridyl group, or pyrazolyl or N.methylpyrazolyl substituted by a prime atom. 40. For example, the compound of claim 33 or a medically acceptable salt thereof, wherein In (I), A6 represents a single bond, and R3 represents a pyridyl or hydroxypyridyl group, or a pyrazolyl or N-methylpyrazolyl group which may be substituted by a C! ~ C4 alkyl group or a halogen atom. 41 · If the compound of any one of the 23rd or 28th in the scope of patent application or a medically acceptable salt thereof, wherein A5 and A6 in the formula (I) are single bonds. 4 2. If the compound of item 41 of the scope of patent application or a medically acceptable salt thereof, wherein R2 in the formula (I) is C which can be substituted] ~ C1G acyclic aliphatic hydrocarbon group, which may be substituted C3 ~ C8 alicyclic hydrocarbon group, C6 ~ C14 aromatic hydrocarbon group which can be substituted, or heterocyclic group which can be substituted, R3 shows C6 ~ Cm aromatic hydrocarbon group which can be substituted or heterocyclic ring which can be substituted base. 43. If the compound of the scope of patent application No. 41 or a medically acceptable salt thereof, wherein R2 in formula (1) is Ci ~ acyclic aliphatic hydrocarbon group, C3 ~ C8 alicyclic hydrocarbon group, may be substituted A phenyl group or a heterocyclic group having 1 to 2 atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in a ring which may be substituted. R3 is a group that may be substituted by one or more CrG alkyl groups. -377- 200526665 (12) Thienyl, pyridyl, furyl, pyrrolyl, pyrazole 44. For example, the salt allowed by the compound in the scope of item 41 of the patent application, wherein R2 in formula (I) is cyclopropyl Vinyl, isopropyl, isobutyl, or 2-methyl-1-propanyl, pyridyl, or pyrazolyl or N.methylpyrazolyl substituted with one alkyl or one phonon atom. 4 5 · As permissible by the compound in the scope of patent application No. 41, wherein R2 in formula (I) is a furanyl or pyrrolyl group which may be substituted by any one or a plurality of alkoxy groups or chlorine atoms. , Pyrazolyl, or phenyl, alkyl, or pyridyl substituted with a halogen atom, or pyrazolyl or N-methylpyrazolyl. 46. A pharmaceutical composition, characterized in that it is formed from the compound according to any one of items 1 to 45 or a medicine thereof, and a pharmaceutically acceptable carrier. 47. A GSK-3 blocking agent characterized by containing a compound according to any one of items 1 to 45 or a medical salt thereof as an active ingredient. 48 · —A therapeutic drug related to GSK-3 disease or one containing any of the medically acceptable salts as the active ingredient in any of claims 1 to 45 of the scope of patent application. 49. If the therapeutic drug of item 48 in the scope of the patent application is related to GSK-3, the disease is one or more selected from diabetes, azimuth disease, neurodegenerative disease, bipolar disorder, outer base, or phenyl. Or it can be medically indicated by methyl, ethyl, amine, R3 is pyridyl or hydroxy_ or it can be medically indicated by ~ C4 alkyl, thienyl, pyridyl, R3 is indicated by 1 or 1 -Salts that are allowed in the scope of patent application for hydroxypyridyl, such as preventive medicines that are technically allowed in the scope of patent application, a compound of one of the characteristics or or preventive medicines, which has diabetic syndrome, traumatic brain injury, Tu-378 · 200526665 (13) People with schizophrenia, inflammatory diseases, cancer, and immunodeficiency. 5 0. — a compound represented by the following formula (Ic), In formula (Ic), the definitions of A2, A3, A4, A5, A6, G], G2, R2, and R3 are the same as the definitions of formula (I) above. Q is a C2 ~ C1G fluorenyl group which may be substituted. Substituted C2 ~ C1G alkoxymethyl, or benzyl which can be substituted. Cao -379- 200526665 VII. Designated representative map: (1) 、 Designated representative map in this case is ... None (2) 、 Simple description of component representative symbols of this representative map: None 8. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: Formula I -5-