Dioxopiperidine derivative and use thereof

Abstract

In the present application, as one of the embodiments, a dioxopiperidine derivative represented by formula (I) (wherein R and L are as defined in the description) is disclosed, which is useful in the medical field and has a growth inhibition effect on, for example, hematopoietic tumors that are blood diseases.

Description

Dioxopiperidine derivatives and their uses

[0001] The present invention relates to embodiments of dioxopiperidine derivatives and the like that are useful in the pharmaceutical field, particularly those that have a growth inhibitory effect on hematopoietic tumors, which are blood diseases.

[0002] Hematopoietic tumors are blood disorders that occur when blood cells, such as red blood cells, white blood cells, and platelets, become cancerous during their differentiation. Among hematopoietic tumors, malignant lymphoma, leukemia, and multiple myeloma are known as the three major hematopoietic tumors, in descending order of the number of patients. The incidence and mortality rates of all cancers in Japan are on the rise for both men and women. In 2020, 945,055 new cases of cancer were diagnosed, including 35,997 cases of malignant lymphoma, 14,272 cases of leukemia, and 7,269 cases of multiple myeloma. The incidence rates per 100,000 population in 2020 were 28.5 cases of malignant lymphoma, 11.3 cases of leukemia, and 5.8 cases of multiple myeloma, accounting for approximately 10% of all cancers. The incidence of malignant lymphoma has been increasing year by year, with cases per 100,000 people in 1985, 1995, 2005, 2011, and 2020 reaching 5.5, 8.9, 13.3, 19.4, and 28.5, respectively. The male-to-female ratio is approximately 3:2, with a male predominance, and the peak age for onset is between 70 and 80 years old (National Cancer Center Cancer Statistics 2016-2020 and Non-Patent Document 1).

[0003] Malignant lymphoma is a general term for malignant tumors derived from lymphocytes, a type of white blood cell. The World Health Organization (WHO) Classification, Revised Fourth Edition (2017), lists over 90 different disease types (see Non-Patent Document 2). Chemotherapy remains the core of drug treatment for malignant lymphoma, and although it is a potentially curable hematologic tumor, the cure rate varies significantly depending on the disease type. Some malignant lymphomas are difficult to treat with chemotherapy (see Non-Patent Document 3). For cases where chemotherapy does not produce a sufficient therapeutic effect, molecular targeted drugs alone or combination therapy of molecular targeted drugs with conventional chemotherapeutic agents has been attempted. For example, in B-cell non-Hodgkin's lymphoma, where the CD20 positivity rate is 90% or higher, the anti-CD20 antibody drug rituximab is used in combination with other drugs. As a specific example, in diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, a combination therapy of rituximab and chemotherapy (e.g., CHOP therapy) is recommended from the initial treatment stage, and rituximab is positioned as an excellent antibody drug (Non-Patent Document 4).

[0004] Other molecular targeted drugs for B-cell non-Hodgkin's lymphoma that have attracted attention include ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and lenalidomide, an immunomodulatory drug. In particular, although lenalidomide improves the prognosis of patients with non-germinal center B cell (GCB) diffuse large B-cell lymphoma, it is less effective against GCB diffuse large B-cell lymphoma. In addition, in a study of lenalidomide in combination with rituximab in patients with recurrent mantle cell lymphoma, the overall response rate was 56%, with 44% of patients being non-responsive. Therefore, the development of a new therapeutic drug effective against malignant lymphoma is desired (Non-Patent Document 5).

[0005] Leukemia is a disease characterized by the overproduction of immature or abnormal white blood cells, which ultimately suppresses the production of normal blood cells and results in symptoms related to blood cytopenia. Leukemia is classified as acute or chronic based on the percentage of blasts or white blood cells in the bone marrow or blood. Acute leukemia is predominantly composed of immature, undifferentiated cells (usually blast-type), and is divided into acute myeloid leukemia and acute lymphoblastic leukemia (AML) (Non-Patent Document 6). Acute myeloid leukemia is a diverse hematopoietic tumor characterized by the autonomous clonal proliferation of immature myeloid cells with impaired differentiation and maturation. Abnormal proliferation of leukemic cells in the bone marrow significantly suppresses normal hematopoietic function, resulting in various symptoms associated with leukopenia and thrombocytopenia. Without appropriate treatment, it is a serious disease that can be fatal within a short period due to infection or bleeding. The basic treatment strategy for newly diagnosed acute myeloid leukemia is intensive chemotherapy aimed at achieving a cure, with multidrug combination therapy being the norm. However, its suitability must be carefully and rigorously assessed based on age, organ function, and overall condition, depending on whether the patient can tolerate chemotherapy-induced organ toxicity and complications (Non-Patent Document 1). The median age at onset of acute myeloid leukemia is approximately 65 years. Currently, elderly patients, for whom intensive chemotherapy is difficult due to organ function or complications, have limited treatment options and a poor prognosis. Recent advances in molecular targeted therapy are changing the nature of acute myeloid leukemia treatment, including for elderly patients. Fms-like tyrosine kinase 3 (FLT3) inhibitors (quizartinib, gilteritinib) enable disease control on outpatient basis, and the B cell / CLL lymphoma 2 (BCL2) inhibitor venetoclax has been shown to be effective in combination with conventional azacitidine or low-dose cytarabine for elderly patients and those with acute myeloid leukemia who are ineligible for intensive chemotherapy. On the other hand, as with conventional intensive chemotherapy, neutropenia and thrombocytopenia have been reported, making outpatient management extremely important when continuing treatment (Non-Patent Document 7). Acute lymphoblastic leukemia is a disease that is common in children, and in adults, there is no difference in the incidence rate by age between 20 and 60 years old, but the incidence increases after the age of 60.Acute lymphoblastic leukemia (ALL) is broadly classified into Ph-positive ALL, which has a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia (Ph) chromosome (t(9;22)), and Ph-negative ALL. In ALL, the ABL1 gene on chromosome 9 fuses with the BCR gene on chromosome 22 to form the BCR-ABL1 fusion gene. The tyrosine kinase activity of this protein induces a constitutive signal downstream, leading to cell proliferation and the development of leukemia. In recent years, tyrosine kinase inhibitors have been introduced for ALL, resulting in remission in almost all cases. Furthermore, pediatric chemotherapy, which primarily uses L-asparaginase and methotrexate, has been introduced for ALL, resulting in remission in approximately 80-90% of cases. However, both diseases have long-term problems such as recurrence and treatment-related complications (Non-Patent Document 8).

[0006] Multiple myeloma is a disease characterized by the neoplastic transformation of plasma cells, which differentiate and mature from B cells, a type of white blood cell. It is characterized by monoclonal (neoplastic) proliferation of plasma cells and increased serum and urinary levels of their product, monoclonal immunoglobulin (M protein) (Non-Patent Document 1). Multiple myeloma is a hematopoietic tumor characterized by anemia, renal damage, bone lesions, and hypercalcemia due to the proliferation of clonal plasma cells. In recent years, the emergence of proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory agents (thalidomide, lenalidomide, pomalidomide), and anti-CD38 antibody drugs (daratumumab, isatuximab), has significantly improved treatment outcomes. However, it remains an incurable disease with a poor prognosis (Non-Patent Document 9). A recent prospective study reported that the overall response rate for relapsed / refractory multiple myeloma patients exposed to these three classes of drugs was 29.8%, with median progression-free survival and overall survival of 4.6 and 12.4 months, respectively. The development of new therapeutic agents and therapies is needed to improve the prognosis of this patient population (Non-Patent Documents 9 and 10). Recently, bispecific T cell-inducing antibodies and chimeric antigen receptor T cell therapy have been developed and introduced into clinical settings, and further improvements in prognosis are expected (Non-Patent Document 11).

[0007] WO 2019 / 146773 (Patent Document 1) describes a compound having a thiophene ring, a triazole ring, and a glutarimide group, but there is no specific disclosure of a compound represented by the following formula (I) in which a side chain is extended from a thiophene ring. J. Med. Chem. 2022: 65(1): 747-756 (Non-Patent Document 12) describes a compound having a thiophene ring, a triazole ring, and a glutarimide group, but there is no specific disclosure of a compound represented by the following formula (I) in which a side chain is extended from a thiophene ring. WO 2022 / 251588 (Patent Document 2) describes a compound having a thiophene ring, a triazole ring, and a glutarimide group, but there is no specific disclosure of a compound represented by the following formula (I) in which a side chain is extended from a thiophene ring. WO 2023 / 059609 (Patent Document 3) describes a compound having a thiophene ring, a triazole ring, and a glutarimide group, but does not specifically disclose a compound represented by the following formula (I) in which a side chain is extended from a thiophene ring.

[0008] International Publication No. 2019 / 146773 International Publication No. 2022 / 251588 International Publication No. 2023 / 059609

[0009] Japanese Society of Hematology Clinical Practice Guidelines for Hematopoietic Tumors, 2023 Edition; Yamaguchi, Journal of the Japanese Society of Internal Medicine, Vol. 110, No. 9, p. 1939, 2021; Suzumiya, Journal of the Japanese Society of Internal Medicine, Vol. 105, No. 9, p. 1761, 2016; NCCN Clinical Practice Guidelines for Oncology, Non-Hodgkin's Lymphoma, 2nd Edition, 2015; Arora M, Ther. Adva. Hematol. 7, No. 4, p. 209, 2016 MDS Manual Professional Edition Overview of Leukemia, 2020 Ishikawa, Journal of the Japanese Society of Internal Medicine, Vol. 111, p. 1344, 2022 Hatta, Journal of the Japanese Society of Internal Medicine, Vol. 111, p. 1351, 2022 Takahashi, Hematology, Vol. 85, No. 4, p. 521, 2023 Mateos MV, Leukemia, Vol. 36, No. 5, p. 1371, 2022 Kuroda, Hematology, Vol. 85, No. 4, p. 372, 2024 Teng M, J. Med. Chem., Vol. 65, No. 1, p. 747, 2022

[0010] An object of the present invention is to provide a novel dioxopiperidine derivative which has high cytostatic activity against cells of hematopoietic tumors such as malignant lymphoma, leukemia, and multiple myeloma, and is useful for the prevention or treatment of hematopoietic tumors, and a medicament, etc. containing the same.

[0011] As a result of intensive research aimed at solving the above problems, the present inventors have found that the compound represented by the following formula (I) has excellent cell growth inhibitory activity against hematopoietic tumor cells, and have completed the present invention based on this novel finding. Specific embodiments of the present invention include, for example, the following. However, the present invention is not limited to these embodiments.

[0012] [1] Formula (I):

[0013]

[0014] [Wherein R represents: (1) partial structural formula (II):

[0015]

[0016] (Wherein, ring A represents a 3- to 8-membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms, and may further contain 1 or 2 silicon atoms as ring-constituting atoms; and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents a substituent, w represents an integer of 0 to 3,

[0017]

[0018] indicates a bond, and * indicates the bonding position to the methylene group; (2) a group represented by partial structural formula (III):

[0019]

[0020] wherein ring A has the same meaning as defined above, and ring B is C ３－８ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a substituent, x represents an integer of 0 to 3,

[0021]

[0022] indicates a bond, and * indicates the bonding position to the methylene group; (3) a group represented by partial structural formula (IV):

[0023]

[0024] (Wherein, ring C is C ３－１２ Cycloalkane or C ６－１４ represents an aromatic carbocyclic ring, ｃ are present on the same or different constituent atoms of ring C, and each independently represents a substituent, y represents an integer of 0 to 3,

[0025]

[0026] indicates a bond, * indicates the position of attachment to a methylene group, L １ is C １－６ represents an alkylene group, and n represents 0 or 1; or (4) a group represented by partial structural formula (V):

[0027]

[0028] (Wherein, ring C has the same meaning as defined above, and ring D is C ３－８ a cycloalkane, wherein ring D is spiro-bonded to ring C or fused to ring C to form a bicyclic ring; z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents a substituent, z represents an integer of 0 to 3,

[0029]

[0030] indicates a bond, * indicates the position of attachment to a methylene group, L ２ is C １－６represents an alkylene group, and n represents 0 or 1.) and L is a group represented by the formula: -NH-CO- or -CO-NH-.] or a salt thereof. *) In the above formula, when L is a group represented by the formula: -NH-CO-, -NH is bonded to the benzene ring, and when L is a group represented by the formula: -CO-NH-, -CO is bonded to the benzene ring. The same applies hereinafter in this specification. [2] R is a compound represented by (1) partial structural formula (II):

[0031]

[0032] (Wherein, w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an optionally substituted C ３－８ 6) an optionally substituted C ６－１４ 7) an optionally substituted C ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ (2) a group represented by partial structural formula (III):

[0033]

[0034] (wherein x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an optionally substituted C ３－８ 6) an optionally substituted C ６－１４7) an optionally substituted C ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ (3) a group represented by partial structural formula (IV):

[0035]

[0036] (Wherein, y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an optionally substituted C ３－８ 6) an optionally substituted C ６－１４ 7) an optionally substituted C ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ (4) a group represented by partial structural formula (V):

[0037]

[0038] (Wherein, z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an optionally substituted C ３－８ 6) an optionally substituted C ６－１４ 7) an optionally substituted C６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ The compound or salt thereof according to the above [1], wherein R is a group represented by the following formula (1): (1) an alkanoyl group, and (2) an alkanoyl group, and (3) an alkanoyl group, and (4) an alkanoyl group, and (5) an alkanoyl group, and (6) an alkanoyl group, and (7) an alkanoyl group, and (8) an alkanoyl group, and (9) an alkanoyl group, and (10) an alkanoyl group, and (11) an alkanoyl group, and (12) an alkanoyl group, and (13) an alkanoyl group, and (14) an alkanoyl group, and (15) an alkanoyl group, and (16) an alkanoyl group, and (17) an alkanoyl group, and (18) an alkanoyl group, and (19) an alkanoyl group, and (20) an alkanoyl group

[0039]

[0040] (Wherein, w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ (2) a group represented by partial structural formula (III):

[0041]

[0042] (wherein x R ｂare present on the same or different constituent atoms of ring B, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ (3) a group represented by partial structural formula (IV):

[0043]

[0044] (Wherein, y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents 1) a halogen atom, 2) a C optionally substituted with 1 to 3 halogen atoms １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ (4) a group represented by partial structural formula (V):

[0045]

[0046] (Wherein, z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ The compound or salt thereof according to the above [1] or [2], wherein R is a group represented by the following formula: (1) a partial structural formula (II):

[0047]

[0048] (Wherein, ring A is 1) a 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocycle containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl groups, and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ an alkanoyl group, and w is an integer from 0 to 3;

[0049]

[0050] is a bond, and * is the bonding position to the methylene group; (2) a group represented by partial structural formula (III):

[0051]

[0052] wherein ring A is a 4- to 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂare present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3;

[0053]

[0054] is a bond, and * is the bonding position to the methylene group; (3) a group represented by partial structural formula (IV):

[0055]

[0056] (Wherein, ring C is C ３－１０ Cycloalkane or C ６－１０ an aromatic carbocyclic ring, and y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents C １－６ is an alkyl group, y is an integer from 0 to 3,

[0057]

[0058] is a bond, * is the bonding position to the methylene group, L １ is C １－６ (4) a group represented by partial structural formula (V):

[0059]

[0060] (Wherein, ring C is C ３－６ It is a cycloalkane, and ring D is C ３－６ a cycloalkane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, z is an integer equal to 0,

[0061]

[0062] is a bond, * is the bonding position to the methylene group, L ２ is C １－６ represents an alkylene group, and n is 0 or 1. The compound or salt thereof according to any one of the above [1] to [3],

[0063] [5] R is a partial structural formula (II):

[0064]

[0065] (wherein ring A is 1) a 6-membered nitrogen-containing saturated heterocyclic ring containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocyclic ring containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl groups, and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group (preferably a 5- to 6-membered nitrogen-containing aromatic heterocycle-oxy group containing 1 to 3 nitrogen atoms as ring-constituting atoms), and 9) C １－６ an alkanoyl group, and w is an integer from 0 to 3;

[0066]

[0067] is a bond, and * is the bonding position to the methylene group.) The compound or salt thereof according to any one of the above [1] to [4]. [6] Ring A is an azasilinane, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents C １－６ or ring A is piperidine, and w R ａare present on the same or different constituent atoms of ring A, and each independently represents 1) C １－６ alkyl group, 2) a halogen atom and C ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 3) halogen atom, cyano group, C １－６ Alkyl groups, and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ 4) an aryloxy group, or 5) a 5- to 14-membered aromatic heterocycle-oxy group (preferably a 5- to 6-membered nitrogen-containing aromatic heterocycle-oxy group containing 1 to 3 nitrogen atoms as ring-constituting atoms), or Ring A is piperazine, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents C １－６The compound or salt thereof according to the above-mentioned [5], wherein the compound is an alkanoyl group. [7] N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-tert-butoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide, The compound or salt thereof according to any one of [1] to [6] above, which is N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-toluyloxy)piperidin-1-yl]methyl}phenyl)acetamide, or an acid addition salt thereof.

[0068] [8] R is a group represented by partial structural formula (III):

[0069]

[0070] wherein ring A is a 4- to 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3;

[0071]

[0072] is a bond, and * is a bonding position to a methylene group.) The compound or salt thereof according to any one of the above [1] to [4]. [9] The compound or salt thereof according to any one of the above [1] to [4], wherein R is a group represented by partial structural formula (III):

[0073]

[0074] (wherein ring A is azetidine or piperidine, and ring B is cyclopropane, cyclobutane, or cyclohexane, and ring B is spiro-bonded to ring A to form a bicyclic ring, the compound according to the above-mentioned [8] or a salt thereof.

[10] N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(6-azaspiro[2.5]octan-6-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, The compound or salt thereof according to any one of the above [1] to [4], [8] or [9], which is 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, 4-(2-azaspiro[3.5]nonan-2-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, or an acid addition salt thereof.

[0075]

[11] R is a group represented by partial structural formula (IV):

[0076]

[0077] (Wherein, ring C is C ３－１０ Cycloalkane or C ６－１０ an aromatic carbocyclic ring, and y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents C １－６ is an alkyl group, y is an integer from 0 to 3,

[0078]

[0079] is a bond, * is the bonding position to the methylene group, L １ is C １－６ represents an alkylene group, and n is 0 or 1. The compound or salt thereof according to any one of the above [1] to [4], wherein ring C is a group represented by the formula:

[12] The compound or salt thereof according to the above

[11] , wherein ring C is cyclohexane, adamantane, or benzene.

[13] The compound or salt thereof according to any one of the above [1] to [4],

[11] , or

[12] , wherein ring C is cyclohexane, adamantane, or benzene.

[0080]

[14] R is a partial structural formula (V):

[0081]

[0082] (Wherein, ring C is C ３－６ It is a cycloalkane, and ring D is C ３－６ a cycloalkane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, z is an integer equal to 0,

[0083]

[0084] is a bond, * is the bonding position to the methylene group, L ２ is C １－６represents an alkylene group, and n is 0 or 1. The compound or salt thereof according to any one of the above [1] to [4], wherein ring C and ring D are cyclohexane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, and n is 0.

[15] The compound or salt thereof according to the above

[14] , wherein ring C and ring D are cyclohexane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, and n is 0.

[16] The compound or salt thereof according to any one of the above [1] to [4],

[14] or

[15] , which is 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, or an acid addition salt thereof.

[0085]

[17] N-{4-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropylpiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(6-azaspiro[2.5]octan-6-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-tert-butylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-cyclohexylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-cyclopropylpiperazin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-neopentylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(difluoromethyl)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(trans-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(cis-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-tert-butoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxy-4-methylpiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(3-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide, N-(4-{[4-(2-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(cyclohexylmethylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(2-adamantylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethylcyclohexylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(benzylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(2-phenylpropan-2-ylamino)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, 4-(2-azaspiro[3.5]nonan-2-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide, The compound or salt thereof according to the above [1], which is N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-toluyloxy)piperidin-1-yl]methyl}phenyl)acetamide, or an acid addition salt thereof.

[0086]

[18] N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, or acid addition salts thereof. The compound or salt thereof according to the above-mentioned [1].

[19] The compound or salt thereof according to any one of the above-mentioned [1] to

[18] , wherein L is a group represented by the formula: -NH-CO-.

[20] The compound or salt thereof according to any one of the above-mentioned [1] to

[18] , wherein L is a group represented by the formula: -CO-NH-.

[0087]

[21] A pharmaceutical comprising the compound or salt thereof according to any one of [1] to

[20] above as an active ingredient.

[22] The pharmaceutical according to

[21] above, which is an inhibitor of hematopoietic tumor cell proliferation.

[23] The pharmaceutical according to

[22] above, which is an agent for preventing or treating blood cancer.

[24] The pharmaceutical according to

[23] above, wherein the blood cancer is leukemia, malignant lymphoma, or multiple myeloma.

[25] A method for inhibiting the proliferation of hematopoietic tumor cells, comprising administering an effective amount of the compound or salt thereof according to any one of [1] to

[20] above to a mammal in need thereof.

[26] A method for preventing or treating blood cancer, comprising administering a prophylactically or therapeutically effective amount of the compound or salt thereof according to any one of [1] to

[20] above to a mammal in need thereof.

[27] The method according to

[26] above, wherein the blood cancer is leukemia, malignant lymphoma, or multiple myeloma.

[28] The compound or salt thereof according to any one of [1] to

[20] above, which is used for inhibiting the proliferation of hematopoietic tumor cells.

[29] The compound or salt thereof according to

[28] above, which is used for the prevention or treatment of blood cancer.

[30] The compound or salt thereof according to

[29] above, wherein the blood cancer is leukemia, malignant lymphoma, or multiple myeloma.

[31] Use of the compound or salt thereof according to any one of [1] to

[20] above, for the manufacture of a medicament.

[32] The use according to

[31] above, for the manufacture of an inhibitor of hematopoietic tumor cell proliferation.

[33] The use according to

[32] above, wherein the inhibitor of hematopoietic tumor cell proliferation is an agent for the prevention or treatment of blood cancer.

[34] The use according to

[33] above, wherein the blood cancer is leukemia, malignant lymphoma, or multiple myeloma.

[0088] The present invention provides, as an embodiment thereof, novel dioxopiperidine derivatives that have high cytostatic activity against hematopoietic tumor cells such as malignant lymphoma, leukemia, and multiple myeloma, and are useful for the prevention or treatment of hematopoietic tumors, as well as medicaments and the like containing the same.

[0089] [Regarding Dioxopiperidine Derivatives] The "dioxopiperidine derivatives" provided by the present invention will be described in detail. In one embodiment of the present invention, a dioxopiperidine derivative represented by the formula (I):

[0090]

[0091] [Wherein R represents: (1) partial structural formula (II):

[0092]

[0093] (Wherein, ring A represents a 3- to 8-membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms, and may further contain 1 or 2 silicon atoms as ring-constituting atoms; and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents a substituent, w represents an integer of 0 to 3,

[0094]

[0095] indicates a bond, and * indicates the bonding position to the methylene group; (2) a group represented by partial structural formula (III):

[0096]

[0097] wherein ring A has the same meaning as defined above, and ring B is C ３－８ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a substituent, x represents an integer of 0 to 3,

[0098]

[0099] indicates a bond, and * indicates the bonding position to the methylene group; (3) a group represented by partial structural formula (IV):

[0100]

[0101] (Wherein, ring C is C ３－１２ Cycloalkane or C ６－１４ represents an aromatic carbocyclic ring, ｃ are present on the same or different constituent atoms of ring C, and each independently represents a substituent, y represents an integer of 0 to 3,

[0102]

[0103] indicates a bond, * indicates the position of attachment to a methylene group, L １ is C １－６ represents an alkylene group, and n represents 0 or 1; or (4) a group represented by partial structural formula (V):

[0104]

[0105] (Wherein, ring C has the same meaning as defined above, and ring D is C ３－８ a cycloalkane, wherein ring D is spiro-bonded to ring C or fused to ring C to form a bicyclic ring; z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents a substituent, z represents an integer of 0 to 3,

[0106]

[0107] indicates a bond, * indicates the position of attachment to a methylene group, L ２ is C １－６ represents an alkylene group, and n represents 0 or 1.), and L is a group represented by the formula: -NH-CO- or -CO-NH-.] (hereinafter also referred to as "compound (I)") or a salt thereof." The definition of each symbol in formula (I) is described in detail below.

[0108] In this specification, when notations such as "Ca-b" (e.g., C1-6) or "Ca-Cb" (e.g., C1-C6) appear, this indicates that the number of carbon atoms constituting the group is a to b (e.g., 1 to 6).

[0109] In the present specification, the "3- to 8-membered nitrogen-containing saturated heterocycle" includes a 3- to 8-membered nitrogen-containing saturated heterocycle having at least one nitrogen atom as a ring-constituting atom. Here, the "heterocycle" includes, for example, an aromatic heterocycle and a non-aromatic heterocycle each containing, as ring-constituting atoms other than carbon atoms, 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms, and oxygen atoms.

[0110] In the present specification, examples of the "aromatic heterocycle" include 5- to 14-membered (preferably 5- to 10-membered) aromatic heterocycles containing, as ring-constituting atoms other than carbon atoms, 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms, and oxygen atoms. Preferred examples of the "aromatic heterocycle" include 5- to 6-membered monocyclic aromatic heterocycles (sometimes abbreviated as 5- to 6-membered aromatic heterocycles) such as thiophene, furan, pyrrole, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, 1,2,4-oxadiazole, 1,3,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole, triazole, tetrazole, and triazine; Benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzotriazole, imidazopyridine, thienopyridine, furopyridine, pyrrolopyridine, pyrazolopyridine, oxazolopyridine, thiazolopyridine, imidazopyrazine, imidazopyrimidine, thienopyrimidine, furopyrimidine, pyrrolopyrimidine, pyrazolopyrimidine, oxazolopyrimidine, thiazolopyridine and 8- to 14-membered fused polycyclic (preferably bicyclic or tricyclic) aromatic heterocycles such as quinazine, pyrazolopyrimidine, pyrazolotriazine, naphtho[2,3-b]thiophene, phenoxathiin, indole, isoindole, 1H-indazole, purine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, carbazole, β-carboline, phenanthridine, acridine, phenazine, phenothiazine, and phenoxazine.

[0111] In the present specification, examples of the "non-aromatic heterocycle" include 3- to 14-membered (preferably 4- to 10-membered) non-aromatic heterocycles containing, as ring-constituting atoms other than carbon atoms, 1 to 4 heteroatoms selected from a nitrogen atom, a sulfur atom, and an oxygen atom. Preferable examples of the "non-aromatic heterocycle" include 3- to 8-membered monocyclic non-aromatic heterocycles (sometimes abbreviated as 3- to 8-membered non-aromatic heterocycles) such as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, tetrahydrothiophene, tetrahydrofuran, pyrroline, pyrrolidine, imidazoline, imidazolidine, oxazoline, oxazolidine, pyrazoline, pyrazolidine, thiazoline, thiazolidine, tetrahydroisothiazole, tetrahydrooxazole, tetrahydroisoxazole, piperidine, piperazine, tetrahydropyridine, dihydropyridine, dihydrothiopyran, tetrahydropyrimidine, tetrahydropyridazine, dihydropyran, tetrahydropyran, tetrahydrothiopyran, morpholine, thiomorpholine, azepanine, diazepane, azepine, azocane, diazocane, and oxepane; Examples thereof include 9- to 14-membered fused polycyclic (preferably bi- or tricyclic) non-aromatic heterocycles such as dihydrobenzofuran, dihydrobenzimidazole, dihydrobenzoxazole, dihydrobenzothiazole, dihydrobenzisothiazole, dihydronaphtho[2,3-b]thiophene, tetrahydroisoquinoline, tetrahydroquinoline, 4H-quinolizine, indoline, isoindoline, tetrahydrothieno[2,3-c]pyridine, tetrahydrobenzazepine, tetrahydroquinoxaline, tetrahydrophenanthridine, hexahydrophenothiazine, hexahydrophenoxazine, tetrahydrophthalazine, tetrahydronaphthyridine, tetrahydroquinazoline, tetrahydrocinnoline, tetrahydrocarbazole, tetrahydro-β-carboline, tetrahydroacridine, tetrahydrophenazine, tetrahydrothioxanthene, and octahydroisoquinoline.

[0112] The "heterocycle" has been described in detail above. In this specification, the "nitrogen-containing heterocycle" includes a "heterocycle" containing at least one nitrogen atom as a ring-constituting atom, and the "nitrogen-containing saturated heterocycle" includes a saturated heterocycle among the "nitrogen-containing heterocycle". In this specification, the "3- to 8-membered nitrogen-containing saturated heterocycle" includes a 3- to 8-membered ring among the above "nitrogen-containing saturated heterocycle". Preferred embodiments of the above "3- to 8-membered nitrogen-containing saturated heterocycle" include the following. 1) "4- to 6-membered nitrogen-containing saturated heterocycle" includes, for example, a 4- to 6-membered ring among the above "nitrogen-containing saturated heterocycle". 2) "6-membered nitrogen-containing saturated heterocycle" includes, for example, a 6-membered ring among the above "nitrogen-containing saturated heterocycle".

[0113] In the present specification, examples of "3- to 8-membered nitrogen-containing saturated heterocyclic rings containing 1 to 3 nitrogen atoms as ring-constituting atoms" include those of the above-mentioned "3- to 8-membered nitrogen-containing saturated heterocyclic heterocycles" containing 1 to 3 nitrogen atoms as ring-constituting atoms. Preferred embodiments of the above-mentioned "3- to 8-membered nitrogen-containing saturated heterocyclic rings containing 1 to 3 nitrogen atoms as ring-constituting atoms" include the following. 1) Examples of "4- to 6-membered nitrogen-containing saturated heterocyclic rings containing 1 nitrogen atom as a ring-constituting atom" include those of the above-mentioned "4- to 6-membered nitrogen-containing saturated heterocyclic rings" containing 1 nitrogen atom as a ring-constituting atom. 2) Examples of "6-membered nitrogen-containing saturated heterocyclic rings containing 1 to 2 nitrogen atoms as ring-constituting atoms" include those of the above-mentioned "6-membered nitrogen-containing saturated heterocyclic heterocycles" containing 1 to 2 nitrogen atoms as ring-constituting atoms. 3) "A 6-membered nitrogen-containing saturated heterocyclic ring containing one nitrogen atom as a ring-constituting atom," and examples of the heterocyclic ring include the above-mentioned "6-membered nitrogen-containing saturated heterocyclic heterocyclic ring" containing one nitrogen atom as a ring-constituting atom.

[0114] In this specification, examples of the "3- to 8-membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms and optionally further containing 1 or 2 silicon atoms as ring-constituting atoms" include the above-mentioned "3- to 8-membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms" which may further contain 1 or 2 silicon atoms as ring-constituting atoms. Suitable specific examples of the above-mentioned "3- to 8-membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms" include azetidine, piperidine, piperazine, etc. A preferred embodiment of the above-mentioned "3- to 8-membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms and optionally containing 1 or 2 silicon atoms as ring-constituting atoms" is a "6-membered nitrogen-containing saturated heterocycle containing 1 nitrogen atom as a ring-constituting atom and further containing 1 silicon atom as a ring-constituting atom", and examples of such heterocycles include the above-mentioned "6-membered nitrogen-containing saturated heterocycle containing 1 nitrogen atom as a ring-constituting atom" which further contains 1 silicon atom as a ring-constituting atom. Specific preferred examples of the above-mentioned rings include azasirinane (e.g., 1,3-azasirinane or 1,4-azasirinane, more preferably 1,4-azasirinane).

[0115] In this specification, "C ３－１２ The "cycloalkane" includes 3- to 12-membered saturated carbon rings, such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane, cyclodecane, cycloundecane, cyclododecane, and adamantane. In one preferred embodiment, ３－１０ In the present specification, "C ３－８ The cycloalkane includes the above-mentioned "C ３－１２ Among "cycloalkanes," those having 3 to 8 membered rings are exemplified. ３－６ The cycloalkane includes the above-mentioned "C ３－１２ Among "cycloalkanes," those having 3 to 6 membered rings are mentioned. ６－１４The "aromatic carbocyclic ring" includes a hydrocarbon ring having aromaticity, such as benzene and naphthalene. ６－１０ In the present specification, in the cases where "ring B is spiro-bonded to ring A or fused to form a bicyclic ring" and "ring D is spiro-bonded to ring C or fused to form a bicyclic ring," the "bicyclic ring formed by a spiro bond (spiro ring)" includes a bicyclic ring formed by two rings bonding together and sharing one carbon atom, while the "bicyclic ring formed by condensation (fused ring)" includes a bicyclic ring formed by two rings sharing a side in a one-to-one relationship. Specific preferred examples of the above "spiro ring" and "fused ring" include spiro[5.5]undecane, 2-azaspiro[3.3]heptane, 6-azaspiro[2.5]octane, 2-azaspiro[3.5]nonane, 7-azaspiro[3.5]nonane, 3-azaspiro[5.5]undecane, octahydroquinoline, and the like.

[0116] In the present specification, the "substituents" that may be possessed by each of rings A to D can be appropriately selected by a person skilled in the art, for example, from the viewpoint of improving the efficacy of compound (I). Preferred embodiments thereof include: 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an optionally substituted C ３－８ 6) an optionally substituted C ６－１４ 7) an optionally substituted C ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ Specific examples thereof include an alkanoyl group, etc. More preferred embodiments include: 1a) a halogen atom, 2a) a C group optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3a) C ３－８4a) a cycloalkyl group, 4b) a halogen atom and C ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ Alkoxy group, 5a) C ３－８ cycloalkyloxy group, 6a) halogen atom, cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7a) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8a) a 5- to 14-membered aromatic heterocycle-oxy group, and 9a) C １－６ Specific examples include an alkanoyl group.

[0117] In the present specification, examples of the "halogen atom" include fluorine, chlorine, bromine and iodine.

[0118] In this specification, "C １－６ Examples of the alkyl (group) include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, and 2-ethylbutyl.

[0119] In this specification, "C １－６ Examples of the alkylene group include -CH ２ -, -(CH ２ ) ２ -, -(CH ２ ) ３ -, -(CH ２ ) ４ -, -(CH ２ ) ５ -, -(CH ２ ) ６ -, -CH(CH ３ ) -, -C(CH ３ ) ２ -, -CH(C ２ H５ ) -, -CH(C ３ H ７ )-,-CH(CH(CH ３ ) ２ )-,-(CH(CH ３ )) ２ -, -CH ２ -CH(CH ３ ) -, -CH(CH ３ )-CH ２ -, -CH ２ -CH ２ -C(CH ３ ) ２ -, -C(CH ３ ) ２ -CH ２ -CH ２ -, -CH ２ -CH ２ -CH ２ -C(CH ３ ) ２ -, -C(CH ３ ) ２ -CH ２ -CH ２ -CH ２ - are some examples.

[0120] In this specification, "C ３－８ Examples of the "cycloalkyl (group)" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, and bicyclo[3.2.1]octyl.

[0121] In this specification, "C １－６ Examples of the "alkoxy (group)" include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, and hexyloxy.

[0122] In this specification, "C ６－１４ Examples of the "aryl (group)" include phenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, and 9-anthryl.

[0123] In this specification, "C ３－８Examples of the "cycloalkyloxy (group)" include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, bicyclo[2.2.1]heptyloxy, bicyclo[2.2.2]octyloxy, and bicyclo[3.2.1]octyloxy.

[0124] In this specification, "C ６－１４ Examples of the "aryloxy (group)" include phenoxy, 1-naphthyloxy, 2-naphthyloxy, 1-anthryloxy, 2-anthryloxy, and 9-anthryloxy.

[0125] In the present specification, the term "5- to 14-membered aromatic heterocycle-oxy group" refers to a group having a structure in which an oxygen atom constituting a hydroxyl group is substituted with a group formed by removing any one hydrogen atom from a 5- to 14-membered aromatic heterocycle. Here, examples of the 5- to 14-membered aromatic heterocycle include the 5- to 14-membered "aromatic heterocycle" described above, preferably a 5- to 6-membered monocyclic aromatic heterocycle, and more preferably a 5- to 6-membered nitrogen-containing aromatic heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms (e.g., imidazole, pyrazole, thiazole, isothiazole, pyridine, pyrazine, pyrimidine, pyridazine, 1,2,4-oxadiazole, 1,3,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole, triazole, tetrazole, triazine, etc.).

[0126] In this specification, "C １－６ Examples of the "alkanoyl group" include acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 3-methylbutanoyl, 2-methylbutanoyl, 2,2-dimethylpropanoyl, hexanoyl, and heptanoyl.

[0127] The "dioxopiperidine derivative" in this embodiment is as described above as compound (I), and other preferred embodiments of the dioxopiperidine derivative will be described below one by one.

[0128] [Compound (IA)] R is (1) a compound represented by partial structural formula (II):

[0129]

[0130] (wherein ring A is 1) a 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocycle containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ an alkanoyl group, and w is an integer from 0 to 3;

[0131]

[0132] is a bond, and * is the bonding position to the methylene group; (2) a group represented by partial structural formula (III):

[0133]

[0134] wherein ring A is a 4- to 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3;

[0135]

[0136] is a bond, and * is the bonding position to the methylene group; (3) a group represented by partial structural formula (IV):

[0137]

[0138] (Wherein, ring C is C ３－１０ Cycloalkane or C ６－１０ an aromatic carbocyclic ring, and y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents C １－６ is an alkyl group, y is an integer from 0 to 3,

[0139]

[0140] is a bond, * is the bonding position to the methylene group, L １ is C １－６ (4) a group represented by partial structural formula (V):

[0141]

[0142] (Wherein, ring C is C ３－６ It is a cycloalkane, and ring D is C ３－６ a cycloalkane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, z is an integer equal to 0,

[0143]

[0144] is a bond, * is the bonding position to the methylene group, L ２ is C １－６ represents an alkylene group, and n is 0 or 1. Compound (I) or a salt thereof.

[0145] [Compound (IA-1)] R is a compound represented by partial structural formula (II):

[0146]

[0147] (wherein ring A is 1) a 6-membered nitrogen-containing saturated heterocyclic ring containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocyclic ring containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ 6) a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryloxy group, 7) halogen atom and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group (preferably a 5- to 6-membered nitrogen-containing aromatic heterocycle-oxy group containing 1 to 3 nitrogen atoms as ring-constituting atoms), and 9) C １－６ an alkanoyl group, and w is an integer from 0 to 3;

[0148]

[0149] is a bond, and * is the bonding position to the methylene group.) Compound (IA) or a salt thereof.

[0150] [Compound (IA-1-a)] Ring A is azasilinane, and w R ａare present on the same or different constituent atoms of ring A (preferably silicon atoms), and each independently represents C １－６ or ring A is piperidine, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) C １－６ alkyl group, 2) a halogen atom and C ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 3) halogen atom, cyano group, C １－６ Alkyl group and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ An aryloxy group (more preferably a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ A phenoxy group optionally substituted with 1 to 3 identical or different groups selected from an alkoxy group, more preferably a halogen atom, a cyano group, C １－６ Alkyl group and C １－６ a phenoxy group optionally substituted at the ortho- or para-position by 1 to 2 identical or different groups selected from alkoxy groups), or 4) a 5- to 14-membered aromatic heterocycle-oxy group (preferably a 5- to 6-membered nitrogen-containing aromatic heterocycle-oxy group containing 1 to 3 nitrogen atoms as ring-constituting atoms, more preferably a pyridyloxy group, and even more preferably a 3- or 4-pyridyloxy group), or Ring A is piperazine, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents C １－６ The compound (IA-1) or a salt thereof, wherein R is an alkanoyl group.

[0151] [Compound (I-A-1-b)] N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-tert-butoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide, or acid addition salts thereof. Compound (I-A-1-a) or a salt thereof, and / or 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide, Compound (I-A-1-a) or a salt thereof, which is N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-toluyloxy)piperidin-1-yl]methyl}phenyl)acetamide, or an acid addition salt thereof.

[0152] [Compound (IA-2)] R is a compound represented by partial structural formula (III):

[0153]

[0154] wherein ring A is a 4- to 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3;

[0155]

[0156] is a bond, and * is the position of attachment to the methylene group.) Compound (I) or a salt thereof.

[0157] [Compound (IA-2-a)] R is a compound represented by partial structural formula (III):

[0158]

[0159] Compound (I-A-2) or a salt thereof, wherein ring A is azetidine or piperidine, and ring B is cyclopropane, cyclobutane, or cyclohexane, and ring B is spiro-bonded to ring A to form a bicyclic ring. Examples of the bicyclic ring include 2-azaspiro[3.5]nonane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 3-azaspiro[5.5]undecane, and 6-azaspiro[2.5]octane.

[0160] [Compound (I-A-2-b)] N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(6-azaspiro[2.5]octan-6-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, or an acid addition salt thereof, and / or 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, 4-(2-azaspiro[3.5]nonan-2-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, or an acid addition salt thereof, Compound (I-A-2-a) or a salt thereof.

[0161] [Compound (IA-3)] R is a compound represented by partial structural formula (IV):

[0162]

[0163] (Wherein, ring C is C ３－１０ Cycloalkane or C６－１０ an aromatic carbocyclic ring, and y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents C １－６ is an alkyl group, y is an integer from 0 to 3,

[0164]

[0165] is a bond, * is the bonding position to the methylene group, L １ is C １－６ represents an alkylene group, and n is 0 or 1. Compound (I) or a salt thereof.

[0166] [Compound (IA-3-a)] The compound (IC) or a salt thereof, wherein ring C is cyclohexane, adamantane, or benzene.

[0167] [Compound (I-A-3-b)] Compound (I-A-3-a) or a salt thereof, which is 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(2-phenylpropan-2-ylamino)methyl]phenyl}acetamide or an acid addition salt thereof. [Compound (I-A-4)] Compound (I-A-4) wherein R is a compound represented by partial structural formula (V):

[0168]

[0169] (Wherein, ring C is C ３－６ It is a cycloalkane, and ring D is C ３－６ a cycloalkane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, z is an integer equal to 0,

[0170]

[0171] is a bond, * is the bonding position to the methylene group, L ２ is C １－６ represents an alkylene group, and n is 0 or 1. Compound (I) or a salt thereof.

[0172] [Compound (I-A-4-1)] The compound (I-A-4) or a salt thereof, wherein ring C and ring D are cyclohexane, and ring D is spiro-bonded to ring C to form a bicyclic ring, and n is 0. Here, an example of the bicyclic ring is spiro[5.5]undecane.

[0173] [Compound (I-A-4-1-a)]

[14] Compound (I-A-4-1) or a salt thereof which is 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, or an acid addition salt thereof, and / or Compound (I-A-4-1) or a salt thereof which is N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, or an acid addition salt thereof.

[0174] [Compound (IB)] N-{4-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropylpiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(6-azaspiro[2.5]octan-6-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-tert-butylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-cyclohexylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-cyclopropylpiperazin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-neopentylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(difluoromethyl)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(trans-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(cis-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-tert-butoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxy-4-methylpiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(3-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide, N-(4-{[4-(2-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(cyclohexylmethylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(2-adamantylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,Compound (I) or a salt thereof, which is N-{4-[(4,4-dimethylcyclohexylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(benzylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, or an acid addition salt thereof, and / or 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(2-phenylpropan-2-ylamino)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, 4-(2-azaspiro[3.5]nonan-2-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide, Compound (I) or a salt thereof, which is N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-toluyloxy)piperidin-1-yl]methyl}phenyl)acetamide, or an acid addition salt thereof.

[0175] [Compound (I-C)] N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, or an acid addition salt thereof, Compound (I) or a salt thereof, and / or Compound (I) or a salt thereof, which is N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, or an acid addition salt thereof.

[0176] One embodiment of the "dioxopiperidine derivative" provided by the present invention has been described in detail above. Another preferred embodiment is, for example, the following derivative: [P-1] Formula (I'):

[0177]

[0178] [Wherein R represents: (1) partial structural formula (II):

[0179]

[0180] (Wherein, ring A represents a 3- to 8-membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms, and may further contain 1 or 2 silicon atoms as ring-constituting atoms; and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents a substituent, w represents an integer of 0 to 3,

[0181]

[0182] indicates a bond, and * indicates the bonding position to the methylene group; (2) a group represented by partial structural formula (III):

[0183]

[0184] wherein ring A has the same meaning as defined above, and ring B is C ３－８ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a substituent, x represents an integer of 0 to 3,

[0185]

[0186] indicates a bond, and * indicates the bonding position to the methylene group; (3) a group represented by partial structural formula (IV'):

[0187]

[0188] (Wherein, ring C is C ３－１２ Cycloalkane or C ６－１４ represents an aromatic carbocyclic ring, ｃ are present on the same or different constituent atoms of ring C, and each independently represents a substituent, y represents an integer of 0 to 3,

[0189]

[0190] represents a bond, * represents the bonding position to the methylene group, and n represents 0 or 1; or (4) a group represented by partial structural formula (V'):

[0191]

[0192] (Wherein, ring C has the same meaning as defined above, and ring D is C ３－８ a cycloalkane, wherein ring D is spiro-bonded to ring C or fused to ring C to form a bicyclic ring; z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents a substituent, z represents an integer of 0 to 3,

[0193]

[0194] represents a bond, * represents the position of bonding to the methylene group, and n represents 0 or 1. A compound represented by the formula: or a salt thereof.

[0195] [P-2] R is (1) a partial structural formula (II):

[0196]

[0197] (Wherein, w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) C ６－１４ aryloxy group, and 7) halogen atoms and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ an aryl group, and the other symbols are the same as those defined for partial structural formula (II) in [P-1] above; (2) a group represented by partial structural formula (III):

[0198]

[0199] (wherein x R ｂare present on the same or different constituent atoms of ring B, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) C ６－１４ aryloxy group, and 7) halogen atoms and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ an aryl group, and the other symbols are the same as the corresponding symbols defined for partial structural formula (III) in [P-1] above; (3) a group represented by partial structural formula (IV'):

[0200]

[0201] (Wherein, y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents 1) a halogen atom, 2) a C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) C ６－１４ aryloxy group, and 7) halogen atoms and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ an aryl group, and the other symbols are the same as those defined for partial structural formula (IV) in [P-1] above; or (4) a group represented by partial structural formula (V'):

[0202]

[0203] (Wherein, z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) C ６－１４ aryloxy group, and 7) halogen atoms and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ an aryl group, and other symbols are the same as the corresponding symbols defined for partial structural formula (V) in [P-1] above.) The compound according to [P-1] above, or a salt thereof.

[0204] [P-3] R is (1) a partial structural formula (II):

[0205]

[0206] (Wherein, ring A is 1) a 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocycle containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) C ６－１４ aryloxy group, and 7) halogen atoms and C１－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl groups, and w is an integer from 0 to 3;

[0207]

[0208] is a bond, and * is the bonding position to the methylene group; (2) a group represented by partial structural formula (III):

[0209]

[0210] wherein ring A is a 4- to 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3;

[0211]

[0212] is a bond, and * is the bonding position to the methylene group; (3) a group represented by partial structural formula (IV'):

[0213]

[0214] (Wherein, ring C is C ３－１０ Cycloalkane or C ６－１０ an aromatic carbocyclic ring, and y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents C １－６ is an alkyl group, y is an integer from 0 to 3,

[0215]

[0216] is a bond, * is the bonding position to the methylene group, and n is 0 or 1; or (4) a group represented by partial structural formula (V'):

[0217]

[0218] (Wherein, ring C is C ３－６ It is a cycloalkane, and ring D is C ３－６ a cycloalkane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, z is an integer equal to 0,

[0219]

[0220] is a bond, * is the bonding position to the methylene group, and n is 0 or 1. The compound or salt thereof according to [P-1] or [P-2] above,

[0221] [P-4] R is a compound represented by partial structural formula (II):

[0222]

[0223] (wherein ring A is 1) a 6-membered nitrogen-containing saturated heterocyclic ring containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocyclic ring containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms, １－６ alkyl group, 3) C ３－８ 4) a cycloalkyl group; ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) C ６－１４ aryloxy group, and 7) halogen atoms and C １－６ C optionally substituted with 1 to 3 identical or different groups selected from alkoxy groups ６－１４ aryl groups, and w is an integer from 0 to 3;

[0224]

[0225] is a bond, and * is the bonding position to the methylene group.) The compound or salt thereof according to any one of [P-1] to [P-3] above.

[0226] [P-5] Ring A is an azasilinane, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents C １－６ or ring A is piperidine, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents a halogen atom and C ３－８ C optionally substituted with 1 to 3 identical or different groups selected from cycloalkyl groups １－６ The compound or salt thereof according to the above [P-4], wherein R is an alkoxy group.

[0227] [P-6] R is a compound represented by partial structural formula (III):

[0228]

[0229] wherein ring A is a 4- to 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６ a cycloalkane, wherein ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3;

[0230]

[0231] is a bond, and * is the bonding position to the methylene group.) The compound or salt thereof according to any one of [P-1] to [P-3] above.

[0232] [P-7] R is a compound represented by partial structural formula (III):

[0233]

[0234] (wherein ring A is azetidine or piperidine, and ring B is cyclopropane, cyclobutane, or cyclohexane, wherein ring B is spiro-bonded to ring A to form a bicyclic ring; or a salt thereof according to the above [P-6].

[0235] [P-8] R is a compound represented by partial structural formula (IV′):

[0236]

[0237] (Wherein, ring C is C ３－１０ Cycloalkane or C ６－１０ an aromatic carbocyclic ring, and y R ｃ are present on the same or different constituent atoms of ring C, and each independently represents C １－６ is an alkyl group, y is an integer from 0 to 3,

[0238]

[0239] is a bond, * is the bonding position to the methylene group, and n is 0 or 1. The compound or salt thereof according to any one of [P-1] to [P-3] above.

[0240] [P-9] The compound or salt thereof according to [P-8] above, wherein ring C is cyclohexane, adamantane, or benzene.

[0241] [P-10] R is a partial structural formula (V'):

[0242]

[0243] (Wherein, ring C is C ３－６ It is a cycloalkane, and ring D is C ３－６ a cycloalkane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, z is an integer equal to 0,

[0244]

[0245] is a bond, * is the bonding position to the methylene group, and n is 0 or 1. The compound or salt thereof according to any one of the above [P-1] to [P-3], wherein ring C and ring D are cyclohexane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, and n is 0. [P-11] The compound or salt thereof according to the above [P-10], wherein ring C and ring D are cyclohexane, wherein ring D is spiro-bonded to ring C to form a bicyclic ring, and n is 0.

[0246] Various embodiments of Compound (I) have been described above in detail. However, in carrying out the present invention, Compound (I) can be used in either the free form or the form of a salt thereof (preferably, a pharmaceutically acceptable salt thereof). Those skilled in the art can carry out the present invention by appropriately selecting either form based on the characteristics of the individual Compound (I) used. Examples of salts of Compound (I) include acid addition salts, salts with bases, and salts with amino acids. Examples of acid addition salts include salts with inorganic acids such as hydrochloric acid, sulfuric acid, hydrobromic acid, and nitric acid, and salts with organic acids such as gluconic acid, oxalic acid, tartaric acid, maleic acid, fumaric acid, succinic acid, malic acid, citric acid, mandelic acid, acetic acid, and methanesulfonic acid. Examples of salts with bases include salts with alkali metals such as sodium and potassium, and alkaline earth metals such as calcium. Specific examples of salts with amino acids include, but are not limited to, salts with amino acids such as glycine, lysine, arginine, ornithine, glutamic acid, and aspartic acid. Of these, acid addition salts are preferred, and when the present compound is used as a medicine, pharmaceutically acceptable salts are particularly preferred.

[0247] When compound (I) or a salt thereof contains optical isomers, stereoisomers, positional isomers, or rotational isomers, these are also included in compound (I), and each can be obtained as a single product by a synthesis method or separation method known per se. For example, when compound (I) contains optical isomers, optical isomers resolved from the compound are also included in compound (I). Here, optical isomers can be produced by a method known per se.

[0248] Compound (I) or a salt thereof may be in the form of a crystal. The crystal of compound (I) or a salt thereof can be produced by crystallizing compound (I) or a salt thereof by applying a crystallization method known per se. The crystal of compound (I) or a salt thereof is excellent in physicochemical properties (e.g., melting point, solubility, stability) and biological properties (e.g., pharmacokinetics (absorbability, distribution, metabolism, excretion), pharmacological effect), and is useful as a pharmaceutical.

[0249] Compound (I) may be labeled with an isotope (e.g., H, C, C, F, S, I). Compound (I) may be a hydrate, a non-hydrate, a non-solvated (e.g., anhydrous), or a solvated (e.g., hydrate). Compound (I) also encompasses deuterium-converted forms in which H is converted to D(D). Compound (I) may also be a pharmaceutically acceptable co-crystal or co-crystal salt. Here, a co-crystal or a co-crystal salt refers to a crystalline substance composed of two or more unique solids at room temperature, each having different physical properties (e.g., structure, melting point, heat of fusion, hygroscopicity, solubility, and stability). A co-crystal or a co-crystal salt can be prepared according to a co-crystallization method known per se.

[0250] Compound (I) may be used as a prodrug, and such use as a prodrug is also encompassed within the embodiments of the present invention. A prodrug of compound (I) is a compound that is converted to compound (I) by a reaction with an enzyme, gastric acid, or the like under physiological conditions in a living body, i.e., a compound that is converted to compound (I) by enzymatic oxidation, reduction, hydrolysis, or the like, or a compound that is converted to compound (I) by hydrolysis, etc., with gastric acid, or the like. Those skilled in the art can design these compounds by methods known per se and produce them from compound (I).

[0251] [Regarding the method for producing compound (I) or a salt thereof] The present invention provides, as one embodiment thereof, a method for producing compound (I) or a salt thereof. The production method is not limited, but examples thereof include the following synthesis scheme. Production method

[0252]

[0253] (In the formula, R is as defined for the compound represented by formula (I) in embodiment [1] described in the section [Means for Solving the Problems] above, and Z represents a formyl group.)

[0254] According to the above-described production method, a compound represented by formula (I) or a salt thereof can be produced by reacting a compound represented by formula (X) or a salt thereof with a compound represented by formula (Y) or a salt thereof in a suitable solvent. The solvent is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include N,N-dimethylacetamide, tetrahydrofuran, dimethyl sulfoxide, and dichloromethane. Compound (X) is typically used in an amount of 1 to 1.5 equivalents relative to compound (Y). The reaction temperature is typically within the range of 1°C to 40°C. The above-described production method is preferably carried out in the presence of a reducing agent (e.g., sodium triacetoxyborohydride) or in the co-presence of an iridium catalyst and a reducing agent (e.g., formic acid) (see, for example, Examples 40 to 51 described below). Compound (X) or a salt thereof can be commercially available, or can be easily obtained by those skilled in the art through synthesis from known raw materials using known methods. Compound (Y) or a salt thereof can be obtained by synthesis, for example, by the methods described in (1) to (9) of Example 1 or (1) to (10) of Example 48 below. Salts of compounds (X) and (Y) include those exemplified for compound (I).

[0255] [Use of Compound (I) or a Salt Thereof] Compound (I) or a salt thereof (hereinafter also collectively referred to as "the compound") has excellent growth inhibitory activity against hematopoietic tumor cell lines, and is therefore useful, for example, as a pharmaceutical based on this effect. The use as a pharmaceutical is one preferred embodiment of the present invention. Pharmaceuticals containing the compound can be used as preventive or therapeutic agents for hematopoietic tumors in mammals (e.g., mice, rats, hamsters, rabbits, cats, dogs, cows, sheep, monkeys, humans, etc.). "Hematopoietic tumors" include leukemia, malignant lymphoma, multiple myeloma, etc. Leukemia is classified into acute leukemia and chronic leukemia, but is not limited thereto. Acute leukemia includes, but is not limited to, acute myeloid leukemia, acute promyelocytic leukemia, and acute lymphoblastic leukemia / lymphoblastic lymphoma. Chronic leukemias include, but are not limited to, chronic myeloid leukemia and chronic lymphocytic leukemia / small lymphocytic lymphoma. Malignant lymphomas are classified into Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma is further classified into classical Hodgkin's lymphoma and nodular lymphocyte-predominant Hodgkin's lymphoma. Non-Hodgkin's lymphoma is further classified into precursor lymphoid neoplasms, mature B-cell neoplasms, and mature T / NK-cell neoplasms. Precursor lymphoid neoplasms are further classified into B-cell lymphoblastic leukemia / lymphoma and T-cell lymphoblastic leukemia / lymphoma. Mature B-cell neoplasms include, but are not limited to, chronic lymphocytic leukemia / small lymphocytic lymphoma, splenic marginal zone lymphoma, follicular lymphoma, MALT lymphoma, lymphoplasmacytic lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, etc. Mature T / NK cell neoplasms include, but are not limited to, peripheral T-cell lymphoma, ALK-positive anaplastic large cell lymphoma, adult T-cell leukemia / lymphoma, extranodal NK / T-cell lymphoma, extranodal nasal NK / T-cell lymphoma, mycosis fungoides, Sézary syndrome, etc.

[0256] Here, "prevention" includes preventing the onset of a disease (all pathologies or one or more pathologies) and delaying the onset of the disease. A "prophylactically effective amount" refers to a dose of the compound sufficient to achieve this purpose. Furthermore, "treatment" includes curing a disease (all pathologies or one or more pathologies), ameliorating the disease, and inhibiting the progression of the disease's severity. A "therapeutically effective amount" refers to a dose of the compound sufficient to achieve this purpose. The dosage of the compound is adjusted appropriately depending on symptoms, age, body weight, general condition, etc., but for humans, the compound can typically be administered in the range of 0.001 to 100 mg, preferably 0.001 to 10 mg, more preferably 0.01 to several mg per day for an adult, every day, every other day, once to several times a week, or in a cyclical administration method with a regular rest period. Furthermore, the compound may be combined with radiation therapy, hormone therapy, biological therapy, or immunotherapy, if necessary.

[0257] The present compound can be used as a preventive or therapeutic agent for the above-mentioned various diseases either directly or by mixing with a pharmaceutically acceptable carrier, etc. to form a pharmaceutical composition (medicine). The present compound can be administered using means and adjuvants commonly used in pharmaceuticals, but a preferred administration method is parenteral administration, in which, for example, the present compound is dissolved or suspended in a pharmaceutically acceptable solvent such as water, physiological saline, an organic solvent, or a glucose solution, and may contain, as an adjuvant, an emulsifier, a suspending agent, a stabilizer, a surfactant, a solubilizer, a diluent, an osmotic pressure adjuster, a pH adjuster, or a buffer, and may be administered by intravenous administration including drip infusion, intramuscular administration, intraperitoneal administration, subcutaneous administration, or by direct injection into a target organ or tissue by other delivery means. The method for formulation is not particularly limited, but for example, the compound is dissolved or suspended in an aqueous solvent such as water for injection, physiological saline, 5% glucose solution, citrate buffer solution, or an organic solvent such as dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMA), ethanol, propylene glycol, glycerin, or the like, diluted with a diluent such as Ringer's solution, L-sodium lactate Ringer's solution, fructose injection, essential amino acid pure crystal injection, or xylitol injection, and adjusted to a pH of 4 to 6 with citrate buffer. At this time, a surfactant such as Cremophor or polyethylene glycol may be used as needed.

[0258] The present invention will be specifically explained below based on examples, test examples, and formulation examples, but the present invention is not limited thereto. Those skilled in the art can modify the embodiments of the present invention in various aspects without departing from the spirit of the present invention, and such modifications are also included within the scope of the present invention.

[0259] Example 1 (Compound 1) N-{4-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide

[0260] (1-1) To a solution of 4-bromothiophene-2-carboxaldehyde (25.0 g, 130.9 mmol) in ethanol (260 ml) was added sodium borohydride (9.9 g, 261.8 mmol) in small portions under an argon atmosphere and ice-cooling, followed by stirring at room temperature for 1 hour. 4 M aqueous hydrochloric acid was added dropwise to the reaction solution under ice-cooling, and the ethanol was evaporated. Water was then added and the mixture was extracted with diethyl ether. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give (4-bromothiophen-2-yl)methanol (25.3 g, quant.) as a yellow oil. 1 H-NMR(CDCl3) δ 7.18 (1H, d, J=1.4Hz), 6.92-6.94 (1H, m), 4.79 (2H, d, J=0.3Hz), 1.42-2.17 (1H, br).

[0261] (1-2) To a solution of (4-bromothiophen-2-yl)methanol (25.3 g, 130.9 mmol) in dichloromethane (260 ml) was added thionyl chloride (19.0 ml, 261.8 mmol) under an argon atmosphere and ice-cooled. The mixture was stirred at room temperature for 3.5 hours, and then thionyl chloride (9.5 ml, 130.9 mmol) was added and stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the residue was added with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give 4-bromo-2-(chloromethyl)thiophene (27.5 g, 99%) as a brown oil. 1 H-NMR(CDCl3) δ 7.21 (1H, d, J=1.4Hz), 6.99-7.02 (1H, m), 4.73 (2H, d, J=0.3Hz).

[0262] (1-3) To a solution of 4-bromo-2-(chloromethyl)thiophene (27.5 g, 130.1 mmol) in dichloromethane (130 ml), water (40 ml), tetra-n-butylammonium bromide (4.2 g, 13.0 mmol), and sodium cyanide (9.6 g, 195.2 mmol) were added and stirred at 60°C for 6 hours. Water was added to the reaction mixture, and the mixture was separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The concentrated residue was purified by column chromatography (hexane / ethyl acetate) to yield 2-(4-bromothiophen-2-yl)acetonitrile (22.1 g, 84%) as a brown oil. 1 H-NMR(CDCl3) δ 7.19 (1H, d, J=1.4Hz), 6.99-7.02 (1H, m), 3.89 (2H, d, J=0.8Hz).

[0263] (1-4) To a solution of 2-(4-bromothiophen-2-yl)acetonitrile (22.1 g, 109.4 mmol) in ethanol (200 ml), water (200 ml) and 85% potassium hydroxide (18.4 g, 278.7 mmol) were added and stirred at 100°C for 1 hour. After cooling the reaction mixture to room temperature, the ethanol was removed by distillation, and the mixture was washed with diethyl ether and the aqueous layer was separated. The separated aqueous layer was acidified with 4 M aqueous hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give 2-(4-bromothiophen-2-yl)acetic acid (22.7 g, 94%) as a brown solid. 1 H-NMR(CDCl3) δ 7.14 (1H, d, J=1.4Hz), 6.89-6.92 (1H, m), 3.85 (2H, d, J=0.6Hz).

[0264] (1-5) To a solution of 2-(4-bromothiophen-2-yl)acetic acid (22.6 g, 102.6 mmol) in acetonitrile (205 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (29.5 g, 153.9 mmol) and 1-hydroxybenzotriazole (20.8 g, 153.9 mmol) were added and stirred at room temperature for 30 minutes. 4-Aminobenzyl alcohol (13.9 g, 112.9 mmol) was added and stirred at room temperature for 2 days. The reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give 2-(4-bromothiophen-2-yl)-N-[4-(hydroxymethyl)phenyl]acetamide (33.1 g, 99%) as a brown oil. 1 H-NMR(CDCl3) δ 7.39-7.48 (3H, m), 7.27-7.33 (2H, m), 7.19 (1H, d, J=1.0Hz), 6.95 (1H, brs), 4.64 (2H, s), 3.89 (2H, s), 1.48-1.98 (1H, br).

[0265] (1-6) 2-(4-bromothiophen-2-yl)-N-[4-(hydroxymethyl)phenyl]acetamide (33.1 g, 101.6 mmol) was added with tetrakis(triphenylphosphine)palladium(0) (2.34 g, 2.03 mmol), copper(I) iodide (0.39 g, 2.03 mmol), triphenylphosphine (1.06 g, 4.06 mmol), toluene (200 ml), diisopropylamine (34.3 ml, 243.8 mmol), and trimethylsilylacetylene (28.1 ml, 203.2 mmol), in that order, and the mixture was stirred at 70°C for 21 hours under an argon atmosphere. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The concentrated residue was purified by column chromatography (hexane / ethyl acetate) to give N-[4-(hydroxymethyl)phenyl]-2-{4-[(trimethylsilyl)ethynyl]thiophen-2-yl}acetamide (17.4 g, 50%) as a brown solid. 1H-NMR (CDCl3) δ 7.40-7.45 (3H, m), 7.34-7.39 (1H, br), 7.27-7.32 (2H, m), 7.04 (1H, brs), 4.64 (2H, d, J = 5.0 Hz), 3.86 (2H, s), 1.77 (1H, t, J = 5.6 Hz), 0.24 (9H, s). (1-7) To a solution of N-[4-(hydroxymethyl)phenyl]-2-{4-[(trimethylsilyl)ethynyl]thiophen-2-yl}acetamide (17.4 g, 50.6 mmol) in chloroform (350 mL), manganese(IV) oxide (44.0 g, 506 mmol) was added and stirred at room temperature for 17 hours. The reaction mixture was filtered through Celite, and the filtrate was concentrated. The concentrated residue was purified by column chromatography (hexane / ethyl acetate) to obtain N-(4-formylphenyl)-2-{4-[(trimethylsilyl)ethynyl]thiophen-2-yl}acetamide (13.2 g, 76%) as a brown foam. 1 H-NMR(CDCl3) δ 9.93 (1H, s), 7.81-7.89 (3H, m), 7.68 (2H, d, J=8.5Hz), 7.45 (1H, brs), 7.07 (1H, brs), 3.92 (2H, s), 0.25 (9H, s).

[0266] (1-8) To a solution of N-(4-formylphenyl)-2-{4-[(trimethylsilyl)ethynyl]thiophen-2-yl}acetamide (5.0 g, 14.6 mmol) in methanol (30 mL), potassium carbonate (4.0 g, 29.2 mmol) was added and stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give 2-(4-ethynylthiophen-2-yl)-N-(4-formylphenyl)acetamide (4.2 g, crude) as a brown oil. 1H-NMR(CDCl3) δ 9.92 (1H, s), 7.81-7.87 (2H, m), 7.62-7.70 (3H, m), 7.48 (1H, d, J=1.2Hz), 7.07 (1H, brs), 3.93 (2H, s), 3.05 (1H, s).

[0267] (1-9) 2-(4-ethynylthiophen-2-yl)-N-(4-formylphenyl)acetamide (3.9 g, 14.6 mmol) was mixed with 3-azidopiperidine-2,6-dione (2.3 g, 14.6 mmol), copper(I) iodide (0.3 g, 1.5 mmol), tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (0.8 g, 1.5 mmol), and acetonitrile (30 ml) and stirred under an argon atmosphere at room temperature for 2 days. Acetonitrile (300 ml) was added to the reaction mixture and stirred at room temperature for 30 minutes, after which the solid was collected by filtration. Acetone (100 ml) was added to the collected solid and stirred at room temperature for 30 minutes, after which the solid was collected by filtration. The collected solid was purified by recrystallization (dimethyl sulfoxide / ethanol) to obtain a brown solid of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (2.4 g, 39%). 1 H-NMR(DMSO) δ 11.25 (1H, s), 10.67 (1H, s), 9.89 (1H, s), 8.51 (1H, s), 7.80-7.91 (4H, m), 7.71 (1H, d, J=1.0Hz), 7.40 (1H, brs), 5.84 (1H, dd, J=4.5, 12.5Hz), 3.99 (2H, s), 2.80-2.97 (1H, m), 2.59-2.78 (2H, m), 2.27-2.42 (1H, m).

[0268] (1-10) To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.40 g, 0.94 mmol) in N,N-dimethylacetamide (12 ml), 4,4-difluoropiperidine hydrochloride (0.15 g, 0.94 mmol), sodium acetate (0.08 g, 0.94 mmol), dichloromethane (12 ml), and sodium triacetoxyborohydride (0.38 g, 1.41 mmol) were added and stirred at room temperature for 19 hours under an argon atmosphere. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The concentrated residue was purified by column chromatography (dichloromethane / methanol). After concentration, diethyl ether was added and the solid was collected by filtration to give N-{4-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.19 g, 38%) as a pale yellow solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.23 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.52-7.59 (2H, m), 7.37 (1H, d, J=1.1Hz), 7.21-7.27 (2H, m), 5.83 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.48 (2H, s), 2.82-2.97 (1H, m), 2.59-2.76 (2H, m), 2.45 (4H, brt, J=5.0Hz), 2.30-2.40 (1H, m), 1.84-2.03 (4H, m).

[0269] Example 2 (Compound 2) N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 ml) was added 4,4-dimethyl-1,4-azasilinane (0.03 g, 0.24 mmol), dichloromethane (3 ml), sodium triacetoxyborohydride (0.13 g, 0.48 mmol), and 2-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol). (mmol) was added and stirred at room temperature under an argon atmosphere for 18.5 hours. Ethyl acetate was added to the reaction mixture, which was then extracted with water. The aqueous layer was concentrated and then azeotroped with toluene. Acetonitrile was added to the concentrated residue, which was then filtered. The filtrate was purified by column chromatography (amino silica gel: acetonitrile). After concentration, diethyl ether was added and the solid was collected by filtration to give N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.10 g, 75%) as a pale yellow solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.26 (1H, brs), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.56 (2H, brd, J=8.0Hz), 7.38 (1H, d, J=1.2Hz), 7.20-7.33 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.91 (2H, s), 3.44-3.70 (2H, br), 2.56-2.97 (7H, m), 2.30-2.40 (1H, m), 0.62-0.85 (4H, br), 0.05 (6H, s).

[0270] Example 3 (Compound 3) N-{4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide hydrochloride A solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) in N,N-dimethylacetamide (6 ml) was added with 4,4-dimethylpiperidine hydrochloride (0.07 g, 0.47 mmol), sodium acetate (0.04 g, 0.47 mmol), dichloromethane (6 ml), sodium triacetoxyborohydride (0.25 g, 0.94 mmol), and the resulting mixture was stirred for 1 hour at 47°C for 1 hour. (mmol) was added and stirred at room temperature for 18 hours under an argon atmosphere. Ethyl acetate was added to the reaction mixture, which was then extracted with water. The aqueous layer was concentrated, and toluene was added and the mixture was concentrated. Acetonitrile was added to the concentrated residue, which was then filtered. The filtrate was purified by column chromatography (amino silica gel: acetonitrile) and concentrated. 4 M hydrochloric acid / ethyl acetate (2 ml) was added to the concentrated residue, and the mixture was stirred at room temperature for 18 hours. After concentrating the reaction mixture, acetonitrile was added, and the solid was collected by filtration to give N-{4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide hydrochloride (0.12 g, 47%) as a white solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.50 (1H, s), 9.63 (1H, brs), 8.51 (1H, s), 7.66-7.72 (3H, m), 7.45-7.51 (2H, m), 7.39 (1H, d, J=1.1Hz), 5.84 (1H, dd, J=5.2, 12.7Hz), 4.24 (2H, d, J=5.4Hz), 3.95 (2H, s), 3.08-3.18 (2H, m), 2.83-3.07 (3H, m), 2.59-2.75 (2H, m), 2.30-2.40 (1H, m), 1.55-1.67 (2H, m), 1.44-1.52 (2H, m), 0.99(3H, s), 0.94 (3H, s).

[0271] Example 4 (Compound 4) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropylpiperidin-1-yl)methyl]phenyl}acetamide

[0113] In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-isopropylpiperidine (0.04 ml, 0.24 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropylpiperidin-1-yl)methyl]phenyl}acetamide (0.04 g, 33%) was obtained as a white solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.51-7.56 (2H, m), 7.37 (1H, d, J=1.0Hz), 7.17-7.25 (2H, m), 5.83 (1H, dd, J=5.3, 12.8Hz), 3.90 (2H, s), 3.35 (2H, s), 2.76-2.95 (3H, m), 2.60-2.75 (2H, m), 2.30-2.40 (1H, m), 1.75-1.87 (2H, m), 1.55 (2H, brd, J=12.2Hz), 1.32-1.43 (1H, m), 1.07-1.22 (2H, m), 0.90-1.02 (1H, m), 0.83 (6H, d, J=6.8Hz).

[0272] Example 5 (Compound 5) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide hydrochloride To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.70 g, 1.65 mmol) in N,N-dimethylacetamide (20 ml) was added spiro[5.5]undecan-3-amine hydrochloride (0.34 g, 1.65 mmol), sodium acetate (0.14 g, 1.65 mmol), dichloromethane (20 ml), and the mixture was stirred for 1 hour. ml) and sodium triacetoxyborohydride (1.40 g, 6.60 mmol) were added, and the mixture was stirred under an argon atmosphere at room temperature for 23.5 hours. Ethyl acetate was added to the reaction mixture, which was then extracted with water. The aqueous layer was concentrated and azeotroped with toluene. Water was added to the concentrated residue, and the solid was collected by filtration and washed with acetonitrile. 4 M hydrochloric acid / ethyl acetate (10 ml) was added to the resulting solid, and the mixture was stirred at room temperature for 2 hours. The solid was collected by filtration to give 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide hydrochloride (0.72 g, 72%) as a yellow solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.54 (1H, s), 9.02-9.15 (2H, m), 8.52 (1H, s), 7.70 (1H, d, J=1.3Hz), 7.64-7.69 (2H, m), 7.47-7.53 (2H, m), 7.39 (1H, brs), 5.84 (1H, dd, J=5.3, 12.8Hz), 3.74-4.23 (4H, m), 2.81-2.98 (2H, m), 2.59-2.76 (2H, m), 2.29-2.40 (1H, m), 1.80-1.93 (2H, m), 1.53-1.73 (4H, m), 1.32-1.44 (8H, m), 1.13-1.21 (2H, m), 0.93-1.07 (2H, m).

[0273] Example 6 (Compound 6) N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 ml) was added 2-azaspiro[3.5]nonane hydrochloride (0.04 g, 0.24 mmol), sodium acetate (0.02 g, 0.24 mmol), dichloromethane (3 ml), sodium triacetoxyborohydride (0.13 g, 0.48 mmol) was added, and the mixture was stirred under an argon atmosphere at room temperature for 17 hours. Ethyl acetate was added to the reaction mixture, which was then extracted with water. The aqueous layer was concentrated and azeotroped with toluene. Acetonitrile was added to the concentrated residue, which was then filtered. The filtrate was purified by column chromatography (amino silica gel: acetonitrile). After concentration, diethyl ether was added, and the solid was collected by filtration to give N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.07 g, 54%) as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.20 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.49-7.55 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.15-7.22 (2H, m), 5.83 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.49 (2H, s), 2.80-2.96 (5H, m), 2.60-2.75 (2H, m), 2.30-2.40 (1H, m), 1.48-1.58 (4H, m), 1.25-1.39 (6H, m).

[0274] Example 7 (Compound 7) N-{4-[(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 6,6-difluoro-2-azaspiro[3.3]heptane trifluoroacetate (0.06 g, 0.24 mmol) were obtained. From 2,4-dimethyl-1,4-difluoro-2,4-difluoro-3,5-difluoro-2 ... 1 H-NMR(DMSO-d6) δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.49-7.55 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.13-7.22 (2H, m), 5.83 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.45 (2H, s), 3.16 (4H, brs), 2.82-2.96 (1H, m), 2.59-2.75 (6H, m), 2.29-2.41 (1H, m).

[0275] Example 8 (Compound 8) N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 7-azaspiro[3.5]nonane hydrochloride (0.04 g, 0.24 mmol) were prepared. From 2,4-dimethyl-3,5-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.06 g, 46%) was obtained as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4 Hz), 7.50-7.56 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.17-7.24 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.30-3.36 (2H, br), 2.82-2.95 (1H, m), 2.60-2.75 (2H, m), 2.31-2.40 (1H, m), 2.08-2.30 (4H, br), 1.75-1.87 (2H, m), 1.64-1.71 (4H, m), 1.50 (4H, brt, J=5.2Hz).

[0276] Example 9 (Compound 9) N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 3-azaspiro[5.5]undecane hydrochloride (0.05 g, 0.24 mmol) were prepared. From 2,4-dimethyl-3,5-dioxo-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.06 g, 42%) was obtained as a pale red solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.50-7.56 (2H, m), 7.37 (1H, d, J=0.9Hz), 7.18-7.23 (2H, m), 5.83 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.36-3.42 (2H, m), 2.82-2.96 (1H, m), 2.59-2.75 (2H, m), 2.20-2.41 (5H, m), 1.31-1.42 (10H, br), 1.23-1.31 (4H, br).

[0277] Example 10 (Compound 10) N-[4-(6-azaspiro[2.5]octan-6-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 6-azaspiro[2.5]octane hydrochloride (0.04 g, 0.24 mmol) were prepared. From 2,4-dimethyl-3,4-dioxo-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.05 g, 42%) was obtained as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4 Hz), 7.51-7.57 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.20-7.26 (2H, m), 5.83 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.42 (2H, s), 2.82-2.95 (1H, m), 2.59-2.76 (2H, m), 2.29-2.42 (5H, m), 1.19-1.42 (4H, br), 0.22 (4H, brs).

[0278] Example 11 (Compound 11) N-{4-[(4-tert-butylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-(tert-butyl)piperidine hydrochloride (0.04 g, 0.24 mmol) were prepared. From this crude product (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.05 g, 33%) was obtained as a pale red solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.50-7.57 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.18-7.23 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.35 (2H, s), 2.80-2.96 (3H, m), 2.60-2.75 (2H, m), 2.30-2.40 (1H, m), 1.80 (2H, brt, J=11.0Hz), 1.56 (2H, brd, J=12.6Hz), 1.11-1.25 (2H, m), 0.88-0.99 (1H, m), 0.82 (9H, s).

[0279] Example 12 (Compound 12) N-{4-[(4-cyclohexylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.30 g, 0.71 mmol) in N,N-dimethylacetamide (9 ml) was added 4-cyclohexylpiperidine hydrochloride (0.14 g, 0.71 mmol), sodium acetate (0.06 g, 0.71 mmol), dichloromethane (9 ml), sodium triacetoxyborohydride (0.38 g, 1.42 mmol), and the resulting mixture was stirred for 1 hour at 40°C for 1 hour. (mmol) was added and stirred at room temperature under an argon atmosphere for 16.5 hours. Ethyl acetate was added to the reaction mixture, which was then extracted with water. The aqueous layer was concentrated and then azeotroped with toluene. Acetonitrile was added to the concentrated residue, which was then filtered. The collected solid was washed with water and acetonitrile. The filtrate was purified by column chromatography (amino silica gel: acetonitrile) and concentrated. The solids were combined and purified by recrystallization (dimethyl sulfoxide / water) to give N-{4-[(4-cyclohexylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.07 g, 17%) as a brown solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, brs), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.3Hz), 7.50-7.56 (2H, m), 7.37 (1H, brs), 7.16-7.25 (2H, m), 5.83 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.24-3.47 (2H, br), 2.83-2.95 (1H, m), 2.75-2.83 (2H, m), 2.59-2.75 (2H, m), 2.30-2.41 (1H, m), 1.81 (2H, brt, J=11.0Hz), 1.48-1.74 (7H, m), 0.81-1.25 (9H, m).

[0280] Example 13 (Compound 13) N-{4-[(4-cyclopropylpiperazin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 1-cyclopropylpiperazine (0.03 g, 0.24 mmol) were prepared. From 2,4-dimethyl-1,4-dioxo-3,4-dioxo-2,6-dioxo-1,4-dioxo-2,6 ... 1H-NMR(DMSO-d6) δ 11.25 (1H, brs), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.51-7.57 (2H, m), 7.37 (1H, d, J=1.1Hz), 7.17-7.24 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.37 (2H, s), 2.82-2.95 (1H, m), 2.59-2.77 (2H, m), 2.43-2.57 (4H, m), 2.12-2.40 (5H, m), 1.53-1.61 (1H, m), 0.34-0.41 (2H, m), 0.22-0.28 (2H, m).

[0281] Example 14 (Compound 14) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-neopentylpiperazin-1-yl)methyl]phenyl}acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 ml) was added 1-(2,2-dimethylpropyl)piperazine (0.04 g, 0.24 mmol), dichloromethane (3 ml), sodium triacetoxyborohydride (0.13 g, 0.48 mmol), and 1-(2,2-dimethylpropyl)piperazine (0.04 g, 0.24 mmol). (mmol) was added and stirred at room temperature under an argon atmosphere for 17.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The concentrated residue was purified by column chromatography (dichloromethane / methanol). After concentration, diethyl ether was added and the solid was collected by filtration to give 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-neopentylpiperazin-1-yl)methyl]phenyl}acetamide (0.04 g, 25%) as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.23 (1H, brs), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.54 (2H, brd, J=7.3Hz), 7.37 (1H,brs), 7.16-7.27 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.38 (2H, brs), 2.82-2.96 (1H, m), 2.60-2.75 (2H, m), 2.40-2.58 (4H, m), 2.24-2.40 (5H, m), 2.02 (2H, brs), 0.82 (9H, s).

[0282] Example 15 (Compound 15) N-(4-{[4-(difluoromethyl)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-(difluoromethyl)piperidine hydrochloride (0.04 g, 0.24 mmol) were prepared. From 4-(4-(difluoromethyl)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.05 g, 42%) was obtained as an orange solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.52-7.57 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.18-7.25 (2H, m), 5.88 (1H, dt, J=4.6, 56.8Hz), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.39 (2H, s), 2.78-2.96 (3H, m), 2.59-2.75 (2H, m), 2.29-2.40 (1H, m), 1.82-1.94 (2H, m), 1.68-1.81 (1H, m), 1.62 (2H, brd, J=12.4Hz), 1.27-1.40 (2H, m).

[0283] Example 16 (Compound 16) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(trans-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 ml), trans-decahydroquinoline (0.03 g, 0.24 mmol), acetic acid (0.01 ml, 0.24 mmol), dichloromethane (3 ml), sodium triacetoxyborohydride (0.13 g, 0.48 mmol), After stirring at room temperature for 19 hours under an argon atmosphere, the mixture was warmed to 30°C and stirred for 4 days. Ethyl acetate was added to the reaction mixture, which was then extracted with water. The aqueous layer was concentrated and azeotroped with toluene. Acetonitrile was added to the concentrated residue, which was then filtered. The filtrate was purified by column chromatography (amino silica gel: acetonitrile). After concentration, diethyl ether was added, and the solid was collected by filtration to give 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(trans-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide (0.05 g, 38%) as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.20 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.49-7.55 (2H, m), 7.37 (1H, d, J=1.1Hz), 7.16-7.22 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.96 (1H, d, J=13.6Hz), 3.90 (2H, s), 3.03 (1H, d, J=13.6Hz), 2.82-2.96 (1H, m), 2.58-2.76 (3H, m), 2.29-2.41 (2H, m), 2.14-2.24 (1H, m), 0.86-1.93 (13H, m).

[0284] Example 17 (Compound 17) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(cis-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and Rac-(4aR,8aR)-decahydroquinoline (0.03 g, 0.24 mmol) were obtained. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(cis-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide (0.07 g, 50%) was obtained as a white solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.20 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.49-7.55 (2H, m), 7.37 (1H, d, J=1.0Hz), 7.16-7.22 (2H, m), 5.84 (1H, dd, J=5.3, 12.9Hz), 3.96 (1H, d, J=13.8Hz), 3.90 (2H, s), 3.02 (1H, d, J=13.8Hz), 2.82-2.95 (1H, m), 2.58-2.75 (3H, m), 2.29-2.39 (2H, m), 2.14-2.24 (1H, m), 0.85-1.93 (13H, m).

[0285] Example 18 (Compound 18) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-methoxypiperidine hydrochloride (0.04 g, 0.24 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide (0.05 g, 38%) was obtained as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.51-7.56 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.18-7.24 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.37 (2H, s), 3.20 (3H, s), 3.10-3.18 (1H, m), 2.81-2.96 (1H, m), 2.54-2.76 (4H, m), 2.30-2.40 (1H, m), 1.98-2.08 (2H, m), 1.72-1.86 (2H, m), 1.31-1.46 (2H, m).

[0286] Example 19 (Compound 19) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}phenyl)acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 1-(2,2,2-trifluoroethyl)piperazine hydrochloride (0.05 g, 0.24 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}phenyl)acetamide (0.08 g, 63%) was obtained as a white solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.51-7.59 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.17-7.25 (2H, m), 5.83 (1H, dd, J=5.2, 12.7Hz), 3.90 (2H, s), 3.39 (2H, s), 3.13 (2H, q, J=10.2Hz), 2.81-2.96 (1H, m), 2.56-2.76 (6H, m), 2.26-2.42 (5H, m).

[0287] Example 20 (Compound 20) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-isopropoxypiperidine (0.03 g, 0.24 mmol) were prepared. From this reaction mixture (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide (0.05 g, 33%) was obtained as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.50-7.56 (2H, m), 7.37 (1H, d, J=1.2Hz), 7.17-7.25 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.65 (1H, sep, J=6.1Hz), 3.37 (2H, s), 3.27-3.35 (1H, m), 2.83-2.96 (1H, m), 2.56-2.76 (4H, m), 2.30-2.41 (1H, m), 1.96-2.08 (2H, m), 1.68-1.78 (2H, m), 1.30-1.42 (2H, m), 1.04 (6H, d, J=6.1Hz).

[0288] Example 21 (Compound 21) N-{4-[(4-tert-butoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-(tert-butoxy)piperidine (0.04 g, 0.24 mmol) were prepared. From this crude product (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.04 g, 29%) was obtained as a pale yellow solid. 1 H-NMR(DMSO-d6)δ 11.24 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.3Hz), 7.51-7.56 (2H, m), 7.37 (1H, brs), 7.17-7.23 (2H, m), 5.83 (1H, dd, J=5.2, 12.7Hz), 3.90 (2H, s), 3.35-3.46 (3H, m), 2.82-2.96 (1H, m), 2.58-2.75 (4H, m), 2.30-2.40 (1H, m), 2.02 (2H, brt, J=10.7Hz), 1.56-1.67 (2H, m), 1.30-1.42 (2H, m), 1.11 (9H, s).

[0289] Example 22 (Compound 22) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-(2-methylpropoxy)piperidine (0.04 g, 0.24 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide (0.05 g, 38%) was obtained as a white solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.51-7.57 (2H, m), 7.37 (1H, brs), 7.18-7.24 (2H, m), 5.83 (1H, dd, J=5.2, 12.8Hz), 3.90 (2H, s), 3.37 (2H, s), 3.17-3.26 (1H, m), 3.13 (2H, d, J=6.6Hz), 2.82-2.96 (1H, m), 2.55-2.75 (4H, m), 2.30-2.41 (1H, m), 1.98-2.10 (2H, m), 1.66-1.82 (3H, m), 1.34-1.47 (2H, m), 0.84 (6H, d, J=6.7Hz).

[0290] Example 23 (Compound 23) N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 ml) was added 4-(cyclohexyloxy)piperidine (0.04 g, 0.24 mmol), dichloromethane (3 ml), sodium triacetoxyborohydride (0.13 g, 0.48 mmol), and the mixture was stirred for 1 hour at 40°C for 1 hour. (mmol) was added and stirred at room temperature under an argon atmosphere for 22.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate, and the organic layer was separated. The aqueous layer was concentrated, then toluene was added to form an azeotrope, acetonitrile was added, and the mixture was filtered. The filtrate was combined with the organic layer, dried over anhydrous magnesium sulfate, and concentrated. The concentrated residue was purified by column chromatography (ethyl acetate / methanol), concentrated, and diethyl ether was added. The solid was collected by filtration to give N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.05 g, 38%) as a light brown solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.24 (1H, brs), 8.51 (1H, s), 7.69 (1H, d, J=1.0Hz), 7.49-7.62 (2H, m), 7.37 (1H, brs), 7.14-7.31 (2H, br), 5.83 (1H, dd, J=5.1, 12.7Hz), 3.91 (2H, s), 3.21-3.51 (4H, m), 2.82-2.97 (1H, m), 2.56-2.78 (4H, m), 2.30-2.40 (1H, m), 1.92-2.16 (2H, m), 1.01-1.85 (14H, m).

[0291] Example 24 (Compound 24) N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 ml) was added 4-(cyclohexylmethoxy)piperidine (0.05 g, 0.24 mmol), dichloromethane (3 ml), sodium triacetoxyborohydride (0.13 g, 0.48 mmol), and the mixture was stirred for 1 hour at 40°C for 1 hour. (mmol) was added and stirred at room temperature under an argon atmosphere for 22.5 hours. Water was added to the reaction mixture and concentrated, followed by azeotropy with toluene. Acetonitrile was added and filtered, and the filtrate was concentrated. The concentrated residue was purified by column chromatography (ethyl acetate / methanol). After concentration, diethyl ether was added and the solid was collected by filtration to give N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.05 g, 33%) as a light brown solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.25 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.4Hz), 7.50-7.61 (2H, m), 7.38 (1H, brs), 7.18-7.30 (2H, m), 5.84 (1H, dd, J=5.3, 12.8Hz), 3.91 (2H, s), 3.11-3.58 (5H, m), 2.82-2.96 (1H, m), 2.56-2.78 (4H, m), 2.30-2.40 (1H, m), 1.94-2.23 (2H, m), 0.79-1.87 (15H, m).

[0292] Example 25 (Compound 25) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxy-4-methylpiperidin-1-yl)methyl]phenyl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-methoxy-4-methylpiperidine hydrochloride (0.04 g, 0.24 mmol) were prepared. From this reaction mixture (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxy-4-methylpiperidin-1-yl)methyl]phenyl}acetamide (0.04 g, 29%) was obtained as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, brs), 7.53 (2H, brd, J=8.3Hz), 7.37 (1H, brs), 7.21 (2H, brd, J=8.3Hz), 5.83 (1H, dd, J=5.3, 12.8Hz), 3.90 (2H, s), 3.38 (2H, brs), 3.05 (3H, s), 2.82-2.96 (1H, m), 2.59-2.77 (2H, m), 2.30-2.44 (3H, m), 2.14-2.28 (2H, m), 1.57-1.69 (2H, m), 1.36-1.49 (2H, m), 1.06 (3H, s).

[0293] Example 26 (Compound 26) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide In the same manner as in Example 24, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-phenoxypiperidine (0.04 g, 0.24 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide (0.03 g, 21%) was obtained as a light brown solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.23 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.3Hz), 7.52-7.59 (2H, m), 7.38 (1H, brs), 7.20-7.29 (4H, m), 6.85-6.97 (3H, m), 5.83 (1H, dd, J=5.2, 12.7Hz), 4.31-4.42 (1H, br), 3.90 (2H, s), 3.38-3.56 (2H, br), 2.81-2.96 (1H, m), 2.58-2.77 (4H, m), 2.30-2.41 (1H, m), 2.12-2.29 (2H, m), 1.85-2.00 (2H, m), 1.53-1.72 (2H, m).

[0294] Example 27 (Compound 27) N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-cyclopropoxypiperidine (0.03 g, 0.24 mmol) were prepared. From this crude product (2 mmol), N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.04 g, 25%) was obtained as a pale yellow solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, brs), 7.50-7.59 (2H, m), 7.37 (1H, brs), 7.16-7.26 (2H, m), 5.83 (1H, dd, J=5.0, 12.8Hz), 3.90 (2H, s), 3.20-3.47 (4H, m), 2.82-2.98 (1H, m), 2.56-2.77 (4H, m), 2.29-2.42 (1H, m), 2.04 (2H, brt, J=9.9Hz), 1.73-1.88 (2H, m), 1.34-1.51 (2H, m), 034-0.48 (4H, m).

[0295] Example 28 (Compound 28) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide In the same manner as in Example 2, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-ethoxypiperidine (0.03 g, 0.24 mmol) were prepared. From this reaction mixture (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide (0.04 g, 29%) was obtained as a yellow solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.2Hz), 7.51-7.57 (2H, m), 7.37 (1H, brs), 7.18-7.25 (2H, m), 5.83 (1H, dd, J=5.3, 12.8Hz), 3.90 (2H, s), 3.41 (2H, q, J=7.0Hz), 3.37 (2H, brs), 3.18-3.29 (1H, m), 2.82-2.95 (1H, m), 2.57-2.75 (4H, m), 2.30-2.40 (1H, m), 1.95-2.08 (2H, m), 1.73-1.84 (2H, m), 1.32-1.45 (2H, m), 1.08 (3H, t, J=7.0Hz).

[0296] Example 29 (Compound 29) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide In the same manner as in Example 6, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-propoxypiperidine hydrochloride (0.04 g, 0.24 mmol) were prepared. From this reaction mixture (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide (0.04 g, 29%) was obtained as a pale yellow solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.21 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J=1.3Hz), 7.51-7.56 (2H, m), 7.37 (1H, brs), 7.18-7.25 (2H, m), 5.83 (1H, dd, J=5.2, 12.7Hz), 3.90 (2H, s), 3.37 (2H, brs), 3.28-3.35 (2H, m), 3.18-3.27 (1H, m), 2.82-2.96 (1H, m), 2.56-2.76 (4H, m), 2.31-2.41 (1H, m), 2.03 (2H, brt, J=9.8Hz), 1.73-1.84 (2H, m), 1.32-1.52 (4H, m), 0.85 (3H, t, J=7.4Hz).

[0297] Example 30 (Compound 30) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide In the same manner as in Example 1 (1-10), 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-(trifluoromethoxy)piperidine hydrochloride (0.05 g, 0.24 mmol) were prepared. From this reaction mixture (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide (0.04 g, 29%) was obtained as a light brown solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, brs), 7.51-7.58 (2H, m), 7.37 (1H, brs), 7.18-7.27 (2H, m), 5.84 (1H, dd, J=5.2, 12.8Hz), 4.35-4.50 (1H, m), 3.90 (2H, s), 3.41 (2H, s), 2.81-2.97 (1H, m), 2.54-2.78 (4H, m), 2.30-2.42 (1H, m), 2.13-2.26 (2H, m), 1.84-1.96 (2H, m), 1.61-1.75 (2H, m).

[0298] Example 31 (Compound 31) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide 1-(2-Methoxyphenyl)piperazine (0.09 g, 0.47 mmol), dichloromethane (4 ml), and sodium triacetoxyborohydride (0.2 g, 0.93 mmol) were added to a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) in dimethyl sulfoxide (4 ml), and the mixture was stirred under an argon atmosphere at room temperature for 16 hours. Water was added to the reaction mixture, and the mixture was purified by column chromatography (amino silica gel: ethyl acetate) and concentrated. Ethyl acetate: diethyl ether (1:1) was added to the concentrated residue, and the solid was collected by filtration to give 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide (0.06 g, 21%) as a pale yellow solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.25 (1H, s), 8.51 (1H, s), 7.70 (1H, d, J = 1.2Hz), 7.57 (2H, d, J = 8.2Hz), 7.38 (1H, s), 7.27 (2H, d, J = 7.9Hz), 6.82-6.97 (4H, m), 5.84 (1H, dd, J = 4.9, 12.5Hz), 3.91 (2H, s), 3.75 (3H, s), 3.40-3.56 (2H, m), 2.82-3.04 (5H, m), 2.61-2.76 (2H, m), 2.41-2.58 (4H, m), 2.30-2.40 (1H, m).

[0299] Example 32 (Compound 32) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(3-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide In the same manner as in Example 31, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 1-(3-methoxyphenyl)piperazine (0.09 g, 0.47 mmol) were prepared. From this, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(3-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide (0.09 g, 32%) was obtained as a pale yellow solid. 1H-NMR(DMSO-d6) δ 11.25 (1H, s), 10.24 (1H, s), 8.51 (1H, s), 7.70 (1H, d, J = 1.3Hz), 7.57 (2H, d, J = 8.4Hz), 7.38 (1H, s), 7.26 (2H, d, J = 8.4Hz), 7.08 (1H, t, J = 8.2Hz), 6.50 (1H, dd, J = 2.0, 8.2Hz), 6.42 (1H, t, J = 2.1Hz), 6.35 (1H, dd, J = 2.1, 8.1Hz), 5.84 (1H, dd, J = 4.9, 12.5Hz), 3.91 (2H, s), 3.70 (3H, s), 3.46 (2H, s), 3.05-3.15 (4H, m), 2.83-2.96 (1H, m), 2.60-2.75 (2H, m), 2.42-2.54 (4H, m), 2.30-2.40 (1H, m).

[0300] Example 33 (Compound 33) N-(4-{[4-(2-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 31, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 1-(2-chlorophenyl)piperazine (0.09 g, 0.47 mmol) were prepared. From 4-(4-chlorophenyl)piperazin-1-yl)methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.14 g, 50%) was obtained as a light brown solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.24 (1H, s), 8.51 (1H, s), 7.70 (1H, d, J = 1.3Hz), 7.57 (2H, d, J = 8.1Hz), 7.35-7.41 (2H, m), 7.22-7.33 (3H, m), 7.15 (1H, d, J = 7.0Hz), 7.02 (1H, t, J = 7.3Hz), 5.83 (1H, dd, J = 4.9, 12.5Hz), 3.91 (2H, s), 3.49 (2H, brs), 2.82-3.06 (5H, m), 2.60-2.75 (2H, m), 2.42-2.60 (4H, m), 2.30-2.40 (1H, m).

[0301] Example 34 (Compound 34) N-(4-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 31, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 1-(4-chlorophenyl)piperazine (0.09 g, 0.47 mmol) were prepared. From 4-(4-chlorophenyl)piperazin-1-yl)methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.12 g, 43%) was obtained as a white solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.24 (1H, s), 8.51 (1H, s), 7.70 (1H, d, J = 1.3Hz), 7.57 (2H, d, J = 8.4Hz), 7.38 (1H, s), 7.26 (2H, d, J = 8.4Hz), 7.20 (2H, d, J = 9.0Hz), 6.92 (2H, d, J = 9.1Hz), 5.84 (1H, dd, J = 4.9, 12.5Hz), 3.91 (2H, s), 3.46 (2H, s), 3.06-3.17 (4H, m), 2.88-2.96 (1H, m), 2.60-2.76 (2H, m), 2.41-2.57 (4H, m), 2.30-2.40 (1H, m).

[0302] Example 35 (Compound 35) N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide hydrochloride In the same manner as in Example 3, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 3-azaspiro[5.5]undecane hydrochloride (0.09 g, 0.47 mmol) were prepared. From 2,4-dimethyl-3,4-dimethyl-1,4-dimethyl-2 ... 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.51 (1H, s), 9.70-9.83 (1H, br), 8.51 (1H, s), 7.66-7.72 (3H, m), 7.45-7.51 (2H, m), 7.39 (1H, brs), 5.84 (1H, dd, J=5.2, 12.8Hz), 4.22 (2H, d, J=5.3Hz), 3.95 (2H, s), 2.82-3.16 (5H, m), 2.58-2.76 (2H, m), 2.30-2.41 (1H, m), 1.66-1.79 (2H, m), 1.31-1.57 (10H, m), 1.14-1.26 (2H, m).

[0303] Example 36 (Compound 36) N-{4-[(cyclohexylmethylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide hydrochloride Cyclohexanemethylamine (0.03 g, 0.24 mmol), dichloromethane (3 ml), and sodium triacetoxyborohydride (0.25 g, 0.96 mmol) were added to a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 ml), and the mixture was stirred under an argon atmosphere at room temperature for 2 days. Ethyl acetate was added to the reaction mixture, which was then extracted with water. The aqueous layer was concentrated and toluene was added for azeotropy. Acetonitrile was added to the concentrated residue, which was then filtered. The filtrate was purified by column chromatography (amino silica gel: acetonitrile) and concentrated. 4 M hydrochloric acid / ethyl acetate was added to the concentrated residue, which was then stirred at room temperature for 3 days. The reaction mixture was filtered to give N-{4-[(cyclohexylmethylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide hydrochloride (0.05 g, 38%) as an orange solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.45 (1H, s), 8.71-8.87 (2H, br), 8.51 (1H, s), 7.70 (1H, d, J=1.4Hz), 7.64-7.69 (2H, m), 7.44-7.49 (2H, m), 7.39 (1H, brs), 5.84 (1H, dd, J=5.2, 12.7Hz), 4.07 (2H, brt, J=5.2Hz), 3.94 (2H, s), 2.82-2.96 (1H, m), 2.59-2.78 (4H, m), 2.28-2.41 (1H, m), 1.53-1.80 (5H, m), 1.05-1.28 (4H, m), 0.82-0.99 (2H, m).

[0304] Example 37 (Compound 37) N-{4-[(2-adamantylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) in tetrahydrofuran (4 ml) was added 2-aminoadamantane hydrochloride (0.13 g, 0.70 mmol), chloro(pentamethylcyclopentadienyl)(4-dimethylamino-8-quinolinolato)iridium(III) (0.025 g, 0.05 mmol), and 2-aminoadamantane hydrochloride (0.13 g, 0.70 mmol) were added. The mixture was added with N-{4-[(2-adamantylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate (0.06 g, 19%) as a white solid. 1H-NMR(DMSO-d6)δ 11.27 (1H, brs), 10.36 (1H, s), 8.51 (1H, s), 7.69 (1H, s), 7.62 (2H, d, J = 8.3Hz), 7.43 (2H, d, J = 8.3Hz), 7.39 (1H, s), 5.84 (1H, dd, J = 4.9, 12.5Hz), 4.01 (2H, brs), 3.93 (2H, s), 3.05 (1H, brs), 2.83-2.96 (1H, m), 2.59-2.76 (2H, m), 2.30-2.40 (1H, m), 1.46-2.12 (14H, m).

[0305] Example 38 (Compound 38) N-{4-[(4,4-dimethylcyclohexylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate In the same manner as in Example 37, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 2,2-dimethylcyclohexylamine (0.09 g, 0.70 mmol) were prepared. From 2,4-dimethylcyclohexylamino-4,4-dimethylphenyl-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate (0.06 g, 19%) was obtained as a white solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.46 (1H, s), 8.52 (1H, s), 7.70 (1H, s), 7.62-7.73 (2H, m), 7.39 (1H, s), 7.36-7.51 (2H, m), 5.84 (1H, dd, J = 3.7, 11.9Hz), 4.09 (2H, brs), 3.95 (2H, brs), 2.81-2.96 (2H, m), 2.60-2.76 (2H, m), 2.30-2.40 (1H, m), 1.82-1.96 (2H, m), 1.48-1.64 (2H, m), 1.34-1.47 (2H, m), 1.10-1.25 (2H, m), 0.89 (6H, s).

[0306] Example 39 (Compound 39) N-{4-[(benzylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide hydrochloride In the same manner as in Example 36, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and benzylamine (0.03 g, 0.24 mmol) were prepared. From the crude oil (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide hydrochloride (0.05 g, 38%) was obtained as a yellow solid. 1 H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.48 (1H, s), 9.31-9.53 (2H, br), 8.51 (1H, s), 7.64-7.73 (3H, m), 7.36-7.56 (8H, m), 5.84 (1H, dd, J=5.2, 12.7Hz), 4.06-4.18 (4H, m), 3.95 (2H, s), 2.81-2.97 (1H, m), 2.60-2.76 (2H, m), 2.28-2.41 (1H, m).

[0307] Example 40 (Compound 40) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(2-phenylpropan-2-ylamino)methyl]phenyl}acetamide oxalate To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) in tetrahydrofuran:dimethyl sulfoxide (2:1, 3 mL) was added cumylamine (0.09 g, 0.70 mmol), chloro(pentamethylcyclopentadienyl)(4-dimethylamino-8-quinolinolato)iridium(III) (catalytic amount), and formic acid (0.05 mL, 1.4 mmol) was added and stirred at room temperature for 16 hours. After completion of the reaction, the mixture was subjected to column chromatography (ethyl acetate / methanol) and concentrated. The residue was dissolved in dimethyl sulfoxide (2 mL), and ethyl acetate (200 mL) and triethylamine (1 mL) were added. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), and oxalic acid (0.06 g) and ethyl acetate (20 mL) were added in that order. The solid was collected by filtration to give 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(2-phenylpropan-2-ylamino)methyl]phenyl}acetamide oxalate (0.07 g, 23%) as a gray solid. 1H-NMR(DMSO-d6)δ 11.00-11.44 (1H, br), 10.38 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J = 1.2Hz), 7.55 (2H, d, J = 7.6Hz), 7.50-7.67 (2H, m), 7.29-7.49 (4H, m), 7.26 (2H, d, J = 8.1Hz), 5.84 (1H, dd, J = 4.9, 12.5Hz), 3.92 (2H, s), 3.46-3.62 (2H, m), 2.82-2.97 (1H, m), 2.60-2.76 (2H, m), 2.30-2.40 (1H, m), 1.63 (6H, s)

[0308] Example 41 (Compound 41) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide oxalate In the same manner as in Example 40, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 1-pivaloyl-piperazine (0.12 g, 0.70 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide oxalate (0.05 g, 16%) was obtained as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.24 (1H, s), 10.33 (1H, s), 8.51 (1H, s), 7.70 (1H, d, J = 1.2Hz), 7.61 (2H, d, J = 8.4Hz), 7.38 (1H, s), 7.32 (2H, d, J = 8.4Hz), 5.84 (1H, dd, J = 4.9, 12.4Hz), 3.92 (2H, s), 3.77 (2H, s), 3.52-3.69 (4H, m), 2.82-2.96 (1H, m), 2.58-2.75 (6H, m), 2.30-2.40 (1H, m), 1.17 (9H, s)

[0309] Example 42 (Compound 42) N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate In the same manner as in Example 40, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 2-(4-piperidinyloxy)benzonitrile (0.14 g, 0.70 mmol) were prepared. From 1 mmol), N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate (0.05 g, 15%) was obtained as a white solid. 1H-NMR(DMSO-d6)δ 11.24 (1H, s), 10.37 (1H, s), 8.51 (1H, s), 7.73 (1H, dd, J = 1.6, 7.7Hz), 7.70 (1H, d, J = 1.3Hz), 7.59-7.68 (3H, m), 7.39 (1H, s), 7.39 (2H, d, J = 8.3Hz), 7.33 (1H, d, J = 8.6Hz), 7.10 (1H, t, J = 7.5Hz), 5.83 (1H, dd, J = 5.0, 12.5Hz), 4.69-4.80 (1H, m), 3.96 (2H, s), 3.93 (2H, s), 2.69-3.10 (2H, m), 2.76-2.95 (3H, m), 2.59-2.75 (2H, m), 2.30-2.41 (1H, m), 2.02-2.16 (2H, m), 1.80-1.95 (2H, m)

[0310] Example 43 (Compound 43) N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate In the same manner as in Example 40, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 4-(4-piperidinyloxy)benzonitrile (0.14 g, 0.70 mmol) were prepared. From 1 mmol), N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide oxalate (0.07 g, 21%) was obtained as a brown solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.44 (1H, s), 8.51 (1H, s), 7.76 (2H, d, J = 8.8Hz), 7.70 (1H, d, J = 1.3Hz), 7.66 (2H, d, J = 8.5Hz), 7.41 (2H, d, J = 8.5Hz), 7.39 (1H, s), 7.15 (2H, d, J = 8.9Hz), 5.84 (1H, dd, J = 4.9, 12.5Hz), 4.66-4.77 (1H, m), 4.07 (2H, s), 3.94 (2H, s), 3.04-3.20 (2H, m), 2.82-2.98 (3H, m), 2.60-2.77 (2H, m), 2.30-2.42 (1H, m), 2.02-2.18 (2H, m), 1.78-1.95 (2H, m)

[0311] Example 44 (Compound 44) ​​2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide oxalate In the same manner as in Example 40, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 4-(4-fluorophenoxy)piperidine (0.14 g, 0.70 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide oxalate (0.09 g, 28%) was obtained as a white solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.40 (1H, s), 8.51 (1H, s), 7.70 (1H, d, J = 1.3Hz), 7.65 (2H, d, J = 8.2Hz), 7.34-7.47 (3H, m), 7.06-7.15 (2H, m), 6.95-7.03 (2H, m), 5.84 (1H, dd, J = 5.0, 12.5Hz), 4.42-4.54 (1H, m), 4.01 (2H, s), 3.93 (2H, s), 2.99-3.14 (2H, m), 2.76-2.96 (3H, m), 2.58-2.75 (2H, m), 2.29-2.41 (1H, m), 1.94-2.10 (2H, m), 1.73-1.89 (2H, m)

[0312] Example 45 (Compound 45) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide dioxalate To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) in tetrahydrofuran:dimethyl sulfoxide (2:1, 3 mL) was added 3-(piperidin-4-yloxy)pyridine dihydrochloride (0.18 g, 0.70 mmol). A mixture of chloro(pentamethylcyclopentadienyl)(4-dimethylamino-8-quinolinolato)iridium(III) (catalytic amount), formic acid (0.05 mL, 1.4 mmol), and triethylamine (0.1 mL, 0.7 mmol) was added and stirred at room temperature for 16 hours. After completion of the reaction, the mixture was subjected to column chromatography (ethyl acetate / methanol) and concentrated. The residue was dissolved in dimethyl sulfoxide (2 mL), and ethyl acetate (200 mL) and triethylamine (1 mL) were added. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), and oxalic acid (0.06 g) and ethyl acetate (20 mL) were added in this order. The solid was collected by filtration to give 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide dioxalate (0.07 g, 19%) as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.44 (1H, s), 8.51 (1H, s), 8.32 (1H, d, J = 2.8Hz), 8.17 (1H, dd, J = 1.0, 4.6Hz), 7.70 (1H, d, J = 1.3Hz), 7.66 (2H, d, J = 8.4Hz), 7.37-7.48 (4H, m), 7.32 (1H, dd, J = 4.6, 8.4Hz), 5.84 (1H, dd, J = 4.9, 12.5Hz), 4.61-4.71 (1H, m), 4.07 (2H, s), 3.94 (2H, s), 3.05-3.21 (2H, m), 2.82-2.97 (3H, m), 2.59-2.75 (2H, m), 2.31-2.41 (1H, m), 2.01-2.16 (2H, m), 1.80-1.94 (2H, m)

[0313] Example 46 (Compound 46) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide dioxalate In the same manner as in Example 45, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 4-(piperidin-4-yloxy)pyridine dihydrochloride (0.18 g, 0.70 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide dioxalate (0.11 g, 30%) was obtained as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.17 (1H, s), 10.41 (1H, s), 8.42 (1H, s), 8.33 (2H, d, J = 5.5Hz), 7.61 (1H, s), 7.58 (2H, d, J = 8.3Hz), 7.35 (2H, d, J = 8.0Hz), 7.30 (1H, s), 6.98 (2H, d, J = 5.6Hz), 5.75 (1H, dd, J = 4.6, 12.4Hz), 4.64-4.79 (1H, m), 4.11 (2H, s), 3.85 (2H, s), 3.06-3.22 (2H, m), 2.88-3.04 (2H, m), 2.71-2.87 (1H, m), 2.51-2.69 (2H, m), 2.19-2.32 (1H, m), 1.97-2.14 (2H, m), 1.77-1.94 (2H, m)

[0314] Example 47 (Compound 47) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide oxalate In the same manner as in Example 45, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.20 g, 0.47 mmol) and 4-(2-methoxyphenoxy)piperidine hydrochloride (0.17 g, 0.70 mmol) were prepared. From 2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide oxalate (0.03 g, 9%) was obtained as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.42 (1H, s), 8.51 (1H, s), 7.70 (1H, d, J = 1.4Hz), 7.65 (2H, d, J = 8.5Hz), 7.33-7.50 (3H, m), 7.02 (1H, dd, J = 1.4, 8.0Hz), 6.90-7.00 (2H, m), 6.85 (1H, dt, J = 1.8, 7.5Hz), 5.84 (1H, dd, J = 4.9, 12.5Hz), 4.36-4.45 (1H, m), 4.01 (2H, s), 3.94 (2H, s), 3.72 (3H, s), 2.99-3.14 (2H, m), 2.77-2.94 (3H, m), 2.65-2.75 (2H, m), 2.30-2.40 (1H, m), 1.94-2.07 (2H, m), 1.74-1.89 (2H, m)

[0315] Example 48 (Compound 48) 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide

[0316] (48-1) Acetyl chloride (2.4 mL, 33.3 mmol) was added dropwise to a methanol solution (20 mL) of terephthalaldehydic acid (1.0 g, 6.7 mmol) under ice cooling, and the mixture was stirred at room temperature for 16 hours. After the reaction was completed, water was added and the mixture was extracted with ethyl acetate. The mixture was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to quantitatively obtain terephthalaldehydic acid methyl ester (1.1 g) as a white solid. 1 H-NMR(CDCl3) δ 10.11 (1H, s), 8.20 (2H, d, J = 8.3Hz), 7.96 (2H, d, J = 8.4Hz), 3.97 (3H, s)

[0317] (48-2) Terephthalaldehydic acid methyl ester (6.7 mmol) was added to 1,3-propanediol (2.0 g, 26.6 mmol), toluenesulfonic acid monohydrate (0.13 g, 0.7 mmol), and toluene (30 mL) and heated to reflux for 2 h using a Dean-Stark apparatus. After the reaction was complete, the mixture was cooled, and the organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated to quantitatively obtain 4-(1,3-dioxan-2-yl)benzoic acid methyl ester (1.5 g) as a yellow solid. 1 H-NMR(CDCl3) δ 8.04 (2H, d, J = 8.4Hz), 7.56 (2H, d, J = 8.3Hz), 5.54 (1H, s), 4.23-4.33 (2H, m), 4.00 (2H, dt, J = 2.4, 12.3Hz), 3.91 (3H, s), 2.16-2.31 (1H, m), 1.47 (1H, td, J = 1.2, 13.5Hz)

[0318] (48-3) A solution of 4-(1,3-dioxan-2-yl)benzoic acid methyl ester (6.7 mmol) in a tetrahydrofuran / methanol / water mixture (3:3:1, 35 mL) was ice-cooled, and sodium hydroxide (1.3 g, 33.3 mmol) was added and stirred for 16 hours. After the reaction was complete, the mixture was acidified with hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The resulting solid was washed with hexane to give 4-(1,3-dioxan-2-yl)benzoic acid (1.2 g, 87%) as a white solid. 1 H-NMR(CDCl3) δ 8.09 (2H, d, J = 8.4Hz), 7.58 (2H, d, J = 8.2Hz), 5.56 (1H, s), 4.24-4.33 (2H, m), 4.01 (2H, dt, J = 2.5, 12.3Hz), 2.16-2.32 (1H, m), 1.48 (1H, td, J = 1.2, 13.5Hz)

[0319] (48-4) To a solution of 4-bromothiophene-2-carboxaldehyde (25.7 g, 134.3 mmol) in ethanol (200 mL), sodium borohydride (2.5 g, 67.4 mmol) was added under ice cooling and stirred for 1 hour. 4M hydrochloric acid (67 mL) was added dropwise to the reaction mixture, after which the solvent was evaporated, water was added, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, treated with activated carbon, and the solvent was evaporated to quantitatively obtain (4-bromothiophen-2-yl)methanol (26.5 g) as a pale yellow oil. 1 H-NMR(CDCl3) δ 7.18 (1H, d, J = 1.4Hz), 6.91-6.95 (1H, m), 4.80 (2H, brd, J = 5.4Hz), 1.81 (1H, t, J = 5.9Hz)

[0320] (48-5) To a suspension of (4-bromothiophen-2-yl)methanol (20.2 g, 104.7 mmol), triphenylphosphine (2.8 g, 10.5 mmol), tetrakis(triphenylphosphine)palladium(0) (6.1 g, 5.2 mmol), and copper(I) iodide (998 mg, 5.3 mmol) in toluene (210 mL) was added diisopropylamine (35 mL, 0.25 mol) and trimethylsilylacetylene (43 mL, 0.31 mol) under an argon atmosphere and stirred at 70 °C for 20.5 h. Insoluble matter was removed by filtration, and the concentrated residue was purified by column chromatography (hexane / ethyl acetate) to give {4-[(trimethylsilyl)ethynyl]thiophen-2-yl}methanol (19.5 g, 89%) as a reddish-brown oil. 1 H-NMR(CDCl3) δ 7.41 (1H, d, J = 1.4Hz), 7.02 (1H, brd, J = 1.2Hz), 4.77 (2H, brd, J = 6.0Hz), 1.77 (1H, t, J = 6.1Hz), 0.23 (9H, s)

[0321] (48-6) To a solution of {4-[(trimethylsilyl)ethynyl]thiophen-2-yl}methanol (17.6 g, 83.4 mmol) and diphenylphosphoryl azide (21.5 mL, 95.9 mmol) in tetrahydrofuran (170 mL) was added 1,8-diazabicyclo[5.4.0]undecene (14.5 mL, 97.0 mmol) at room temperature and stirred for 3.5 hours. Acetic acid (1.5 mL, 26 mmol) was added dropwise to the reaction mixture, which was stirred for 10 minutes. The mixture was then diluted with diethyl ether and washed with saturated aqueous sodium bicarbonate, water, and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, treated with activated carbon, and the solvent was evaporated to give crude {[5-(azidomethyl)thiophen-3-yl]ethynyl}trimethylsilane (19.9 g) as a reddish-brown oil. 1 H-NMR(CDCl3) δ 7.44 (1H, d, J = 1.4Hz), 7.04-7.08 (1H, m), 4.43 (2H, brs), 0.24 (9H, s)

[0322] (48-7) The crude product of {[5-(azidomethyl)thiophen-3-yl]ethynyl}trimethylsilane (19.9 g) was dissolved in tetrahydrofuran (330 mL) and water (42 mL), triphenylphosphine (26.3 g, 100.1 mmol) was added, and the mixture was stirred at 40 °C for 20.5 h. The solvent was evaporated, and the residue was azeotroped with toluene and then dissolved in ethyl acetate (400 mL). 4 M hydrogen chloride / ethyl acetate solution (32 mL) was added dropwise at room temperature. The precipitate was collected by filtration and washed with ethyl acetate to give {4-[(trimethylsilyl)ethynyl]thiophen-2-yl}methanamine hydrochloride (16.3 g, 79%) as a milky white solid. 1 H-NMR(DMSO-d6) δ 8.26-8.67 (3H, br), 7.85 (1H, d, J = 1.4Hz), 7.27-7.31 (1H, m), 4.19 (2H, brs), 0.21 (9H, s)

[0323] (48-8) Under an argon atmosphere, a solution of 4-(1,3-dioxan-2-yl)benzoic acid (0.6 g, 2.9 mmol), {4-[(trimethylsilyl)ethynyl]thiophen-2-yl}methanamine hydrochloride (0.7 g, 2.9 mmol) in acetonitrile (10 mL) was added with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.7 g, 3.4 mmol), 1-hydroxybenzotriazole (0.5 g, 3.4 mmol), and triethylamine (0.4 mL, 2.9 mmol) and stirred at room temperature for 16 h. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. A diethyl ether / hexane (1 / 9) solution was added to the residue, and after stirring for 30 minutes, the solid was collected by filtration to give 4-(1,3-dioxan-2-yl)-N-({4-[(trimethylsilyl)ethynyl]thiophen-2-yl}methyl)benzamide (1.1 g, 95%) as a pale red solid. 1 H-NMR(CDCl3) δ 7.77 (2H, d, J = 8.4Hz), 7.55 (2H, d, J = 8.2Hz), 7.37 (1H, d, J = 1.3Hz), 7.05 (1H, d, J = 1.0Hz), 6.35-6.50 (1H, m), 5.53 (1H, s), 4.73 (2H, d, J = 5.4Hz), 4.23-4.32 (2H, m), 4.00 (2H, dt, J = 2.5, 12.3Hz), 2.16-2.30 (1H, m), 1.41-1.51 (1H, m), 0.22 (9H, s)

[0324] (48-9) To a solution of 4-(1,3-dioxan-2-yl)-N-({4-[(trimethylsilyl)ethynyl]thiophen-2-yl}methyl)benzamide (1.1 g, 2.8 mmol) in methanol (20 mL) was added potassium carbonate (1.1 g, 8.2 mmol) and stirred at room temperature for 1 hour. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. 3-Azidopiperidine-2,6-dione (0.5 g, 3.3 mmol), copper(I) iodide (5 mol %), tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (5 mol %), and acetonitrile (20 mL) were added to the resulting residue, and the mixture was stirred at room temperature for 16 hours under an argon atmosphere. After completion of the reaction, the solid was collected by filtration to obtain a white solid of 4-(1,3-dioxan-2-yl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide (1.2 g, 88%). 1 H-NMR(DMSO-d6) δ 11.25 (1H, s), 9.22 (1H, t, J = 5.9Hz), 8.51 (1H, s), 7.88 (2H, d, J = 8.3Hz), 7.69 (1H, d, J = 1.4Hz), 7.50 (2H, d, J = 8.3Hz), 7.40 (1H, d, J = 0.8Hz), 5.83 (1H, dd, J = 4.9, 12.5Hz), 5.57 (1H, s), 4.65 (2H, d, J = 5.8Hz), 4.11-4.19 (2H, m), 3.95 (2H, dt, J = 2.4, 12.3Hz), 2.82-2.96 (1H, m), 2.51-2.75 (2H, m), 2.29-2.40 (1H, m), 1.93-2.09 (1H, m), 1.41-1.49 (1H, m)

[0325] (48-10) To a solution of 4-(1,3-dioxan-2-yl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide (7.6 g, 15.8 mmol) in a tetrahydrofuran / water mixture (10 / 1 100 mL) was added concentrated hydrochloric acid (0.2 mL, 1.5 mmol) and stirred at room temperature for 1 day. DMSO was added until the mixture became homogeneous, and the mixture was stirred at 30°C for 1 day. After completion of the reaction, tetrahydrofuran was added, and the mixture was washed with water and saturated brine, successively. The organic layer was dried over anhydrous magnesium sulfate and concentrated. A diethyl ether / ethyl acetate (1 / 1) solution was added to the residue, and the solid was collected by filtration to obtain N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-formylbenzamide (6.5 g, 98%) as a yellow solid. 1 H-NMR(DMSO-d6) δ 11.26 (1H, s), 10.09 (1H, s), 9.44 (1H, t, J = 5.8Hz), 8.53 (1H, s), 8.09 (2H, d, J = 8.3Hz), 8.02 (2H, d, J = 8.4Hz), 7.71 (1H, d, J = 1.4Hz), 7.44 (1H, d, J = 0.9Hz), 5.84 (1H, dd, J = 4.9, 12.5Hz), 4.70 (2H, d, J = 5.8Hz), 2.82-2.96 (1H, m), 2.67-2.76 (2H, m), 2.31-2.41 (1H, m)

[0326] (48-11) To a solution of N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-formylbenzamide (0.20 g, 0.47 mmol) in tetrahydrofuran:dimethyl sulfoxide (1:1, 2 mL) was added 3-azaspiro[5.5]undecane hydrochloride (0.11 g, 0.57 mmol), chloro(pentamethylcyclopentadienyl)(4-dimethylamino-8-quinolinolato)iridium(III) (catalytic amount), formic acid (0.05 mL, 1.4 mmol), and triethylamine (0.08 mL, 0.57 mmol), and the mixture was stirred at room temperature for 16 hours. After the reaction was complete, the mixture was subjected to column chromatography using ethyl acetate / methanol and concentrated. To the residue, ethyl acetate (200 mL) and triethylamine (1 mL) were added. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated. To the residue, ethyl acetate (5 mL) and diethyl ether (10 mL) were added. The solid was collected by filtration to give 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide (0.08 g, 30%) as a pale yellow solid. 1 H-NMR(DMSO-d6)δ 11.26 (1H, s), 9.13-9.31 (1H, br), 8.52 (1H, s), 7.88 (2H, d, J = 6.4Hz), 7.69 (1H, s), 7.40 (1H, d, J = 0.9Hz), 7.31-7.60 (2H, m), 5.84 (1H, dd, J = 5.0, 12.5Hz), 4.66 (2H, d, J = 5.7Hz), 3.17-3.89 (2H, br), 2.12-3.18 (8H, m), 1.24-1.65 (14H, m)

[0327] Example 49 (Compound 49) N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide In the same manner as in Example 48, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-formylbenzamide (0.20 g, 0.47 mmol) and spiro[5.5]undecan-3-amine hydrochloride (0.12 g, 0.57 mmol) were prepared. From 1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide (0.14 g, 52%) was obtained as a yellow solid. 1 H-NMR(DMSO-d6)δ 9.74-12.67 (1H, m), 9.17 (1H, t, J = 5.9Hz), 8.52 (1H, s), 7.84 (2H, d, J = 8.3Hz), 7.69 (1H, d, J = 1.4Hz), 7.45 (2H, d, J = 8.2Hz), 7.40 (1H, d, J = 1.1Hz), 5.84 (1H, dd, J = 5.0, 12.5Hz), 4.65 (2H, d, J = 5.8Hz), 3.81 (2H, s), 2.81-2.97 (1H, m), 2.58-2.76 (2H, m), 2.28-2.44 (2H, m), 1.49-1.72 (4H, m), 1.13-1.45 (12H, m), 0.97 (2H, dt, J = 3.3, 12.9Hz)

[0328] Example 50 (Compound 50) 4-(2-azaspiro[3.5]nonan-2-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide In the same manner as in Example 48, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-formylbenzamide (0.20 g, 0.47 mmol) and 2-aza-spiro[3.5]nonane hydrochloride (0.09 g, 0.57 mmol) were prepared. From 1,2,3-triazol-4-yl]thiophen-2-yl (2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide (0.05 g, 20%) was obtained as a yellow solid. 1 H-NMR(DMSO-d6)δ 11.26 (1H, s), 9.19 (1H, t, J = 5.9Hz), 8.52 (1H, s), 7.85 (2H, d, J = 8.2Hz), 7.69 (1H, d, J = 1.4Hz), 7.40 (1H, d, J = 1.1Hz), 7.31-7.50 (2H, m), 5.84 (1H, dd, J = 5.0, 12.5Hz), 4.65 (2H, d, J = 5.8Hz), 3.61-3.89 (2H, m), 2.80-3.17 (5H, m), 2.58-2.76 (2H, m), 2.26-2.40 (1H, m), 1.46-1.68 (4H, m), 1.23-1.44 (6H, m)

[0329] Example 51 (Compound 51) N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide To a solution of N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-formylbenzamide (0.20 g, 0.47 mmol) in tetrahydrofuran:dimethyl sulfoxide (1:1, 2 mL) was added 4-isopropylpiperidine (0.07 g, 0.57 mmol), chloro(pentamethylcyclopentadienyl)(4-dimethylamino-8-quinolinolato)iridium(III) (catalytic amount), and formic acid (0.05 ml, 1.4 mmol) was added and stirred at room temperature for 16 hours. After completion of the reaction, the mixture was subjected to column chromatography using ethyl acetate / methanol and concentrated. To the residue, ethyl acetate (200 ml) and triethylamine (1 ml) were added. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated. To the residue, ethyl acetate (5 ml) and diethyl ether (10 ml) were added, and the solid was collected by filtration to give N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide (0.08 g, 32%) as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 9.10-9.28 (1H, br), 8.52 (1H, s), 7.80-8.00 (2H, m), 7.69 (1H, d, J = 1.4Hz), 7.41 (1H, d, J = 0.9Hz), 7.27-7.58 (2H, m), 5.84 (1H, dd, J = 5.0, 12.5Hz), 4.66 (2H, d, J = 5.7Hz), 3.23-3.65 (2H, br), 2.58-3.01 (5H, m), 2.29-2.41 (1H, m), 1.73-2.07 (1H, m), 1.49-1.73 (3H, m), 0.96-1.48 (4H, m), 0.84 (6H, d, J = 6.8Hz)

[0330] Example 52 (Compound 52) N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide In the same manner as in Example 14, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) and 4-(4-chlorophenoxy)piperidine (0.05 g, 0.24 mmol) were prepared. From 4-chlorophenoxy-2-(4-chlorophenoxy)piperidin-1-yl (methanol), N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide (0.05 g, 33%) was obtained as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J = 1.4Hz), 7.55 (2H, d, J = 8.4Hz), 7.38 (1H, brs), 7.26-7.31 (2H, m), 7.23 (2H, d, J = 8.4Hz), 6.93-6.99 (2H, m), 5.83 (1H, dd, J = 5.3, 12.8Hz), 4.31-4.41 (1H, m), 3.90 (2H, s), 3.42 (2H, s), 2.81-2.97 (1H, m), 2.58-2.77 (4H, m), 2.29-2.42 (1H, m), 2.19 (2H, brt, J = 9.4 Hz), 1.85-1.97 (2H, m), 1.53-1.66 (2H, m)

[0331] Example 53 (Compound 53) 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-tolyloxy)piperidin-1-yl]methyl}phenyl)acetamide To a solution of 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-formylphenyl)acetamide (0.10 g, 0.24 mmol) in N,N-dimethylacetamide (3 mL) was added 4-(4-methylphenoxy)piperidine (0.05 g, 0.24 mmol), dichloromethane (3 mL), sodium triacetoxyborohydride (0.13 g, 0.48 mmol), and the resulting mixture was added to a 100 mL N,N-dimethylacetamide (3 mL). (mmol) was added and stirred at room temperature under an argon atmosphere for 22.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The concentrated residue was purified by column chromatography (dichloromethane / methanol). After concentration, ethyl acetate and hexane were added, and the solid was collected by filtration to give 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-toluyloxy)piperidin-1-yl]methyl}phenyl)acetamide (0.06 g, 42%) as a pale yellow solid. 1H-NMR(DMSO-d6)δ 11.25 (1H, s), 10.22 (1H, s), 8.51 (1H, s), 7.69 (1H, d, J = 1.4Hz), 7.55 (2H, d, J = 8.1Hz), 7.38 (1H, brs), 7.23 (2H, d, J = 8.0Hz), 7.05 (2H, d, J = 8.3Hz), 6.81 (2H, d, J = 8.4Hz), 5.83 (1H, dd, J = 5.2, 12.8Hz), 4.23-4.35 (1H, br), 3.90 (2H, s), 3.42 (2H, s), 2.82-2.96 (1H, m), 2.57-2.76 (4H, m), 2.30-2.41 (1H, m), 2.10-2.26 (5H, m), 1.80-1.96 (2H, m), 1.50-1.67 (2H, m)

[0332] Test Example: Growth Inhibition Test Using Various Hematopoietic Tumor Cell Lines The human hematopoietic tumor cell lines used in this test are shown in Table 1.

[0333]

[0334] Each cell line was suspended in RPMI 1640 medium (Nacalai Tesque, hereafter referred to as Medium A) containing 10% fetal bovine serum (Thermo Fisher Scientific), diluted appropriately with 0.4% trypan blue (Sigma-Aldrich), and the number of viable cells was counted using a hemocytometer (Funakoshi). The resulting values ​​were diluted with Medium A to obtain the cell suspensions listed in Table 2, "Prepared cell suspensions of hematopoietic tumor cell lines and seeded cell numbers," and each cell suspension was dispensed into a Falcon 96-well flat-bottom plate (Corning) at 50 μL / well.

[0335]

[0336] Subsequently, 50 μL of a DMSO solution containing the test compound at 0.4-4000 μM (common ratio 10, 5 doses) diluted 200-fold with medium A was added to each well (final concentration of the test compound: 1 nM-10 μM). 50 μL of a DMSO solution diluted 200-fold with medium A was added to the control wells. The incubation temperature was 37°C, 5% CO２ After culturing for 3 days under airflow, a cell proliferation assay was performed according to the instructions attached to the WST-8 kit (Kishida Chemical Co., Ltd.), and the IC value of each compound was calculated. ５０ Table 3 shows the growth inhibitory activity (IC) of the compounds against various hematopoietic tumor cell lines. ５０ The values ​​were expressed in ABCD notation based on the following criteria: A: less than 10 nM, B: 10 nM or more and less than 100 nM, C: 100 nM or more and less than 1 μM, D: 1 μM or more. As shown in Tables 3-1 to 3-3, the compounds of the present invention exhibited much stronger cell growth inhibitory activity against various hematopoietic tumor cell lines than the compound reported in Patent Document 1 (3-[4-(4-methoxythiophen-3-yl)-1H-1,2,3-triazol-1-yl]piperidine-2,6-dione: FPFT-2216).

[0337]

[0338]

[0339]

[0340] Formulation Examples A medicine containing the present compound as an active ingredient can be manufactured, for example, by the following formulation: 1. Injection (1) 10 mg of the compound obtained in Example 1 (2) Appropriate amount of water for injection (3) Appropriate amount of physiological saline or 5% glucose solution The above (1) is dissolved in (2) and diluted with (3) to obtain an injection.

[0341] According to an embodiment of the present invention, there are provided novel dioxopiperidine derivatives that have growth inhibitory activity against various hematopoietic tumor cells and are useful for the prevention or treatment of various hematopoietic tumors, as well as pharmaceuticals and the like containing the same. The present invention is useful in the field of pharmaceuticals.

[0342] This application is based on patent application No. 2023-205252 filed in Japan (filing date: December 5, 2023), the contents of which are incorporated in their entirety herein.

Claims

1. Formula (I): [In the formula, R is: (1) Partial structural formula (II): (Wherein, ring A represents a 3-8 membered nitrogen-containing saturated heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms and optionally containing 1 or 2 silicon atoms as ring-constituting atoms; w R ａ are present on the same or different constituent atoms of ring A, and each independently represents a substituent; w represents an integer of 0 to 3; represents a bond, and * represents the position of attachment to a methylene group; (2) a group represented by partial structural formula (III): (wherein ring A is as defined above, and ring B is C ３－８ a cycloalkane, where ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a substituent, x represents an integer of 0 to 3, represents a bond, and * represents the position of attachment to a methylene group; (3) a group represented by partial structural formula (IV): (Wherein, ring C is C ３－１２ Cycloalkane or C ６－１４ represents an aromatic carbocyclic ring, ｃ are present on the same or different constituent atoms of ring C, and each independently represents a substituent; y represents an integer of 0 to 3; indicates a bond, * indicates the position of attachment to a methylene group, L １ is C １－６ represents an alkylene group, and n represents 0 or 1; or (4) a group represented by partial structural formula (V): (Wherein, ring C has the same meaning as defined above, and ring D is C ３－８ cycloalkane, where ring D is spiro-bonded to ring C or fused to ring C to form a bicyclic ring; z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents a substituent; z represents an integer of 0 to 3; indicates a bond, * indicates the position of attachment to a methylene group, L ２ is C １－６ represents an alkylene group, and n represents 0 or 1; and L is a group represented by the formula: -NH-CO- or -CO-NH-, or a salt thereof.

2. R is (1) a partial structural formula (II): (Wherein, w R ａ are present on the same or different constituent atoms of ring A, and each independently represents: 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an alkoxy group, ３－８ 6) an optionally substituted C ６－１４ 7) an aryloxy group, ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ (2) a group represented by partial structural formula (III): (Wherein, x R ｂ are present on the same or different constituent atoms of ring B, each independently being 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an alkoxy group, ３－８ 6) an optionally substituted C ６－１４ 7) an aryloxy group, ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ (3) a group represented by partial structural formula (IV): (Wherein, y R ｃ are present on the same or different constituent atoms of ring C, each independently being 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an alkoxy group, ３－８ 6) an optionally substituted C ６－１４ 7) an aryloxy group, ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ (4) a group represented by partial structural formula (V): (Wherein, z R ｄ are present on the same or different constituent atoms of ring D, and each independently represents 1) a halogen atom, 2) an optionally substituted C １－６ 3) an optionally substituted C ３－８ 4) an optionally substituted C １－６ 5) an alkoxy group, ３－８ 6) an optionally substituted C ６－１４ 7) an aryloxy group, ６－１４ aryl group, 8) an optionally substituted 5- to 14-membered aromatic heterocycle-oxy group, and 9) an optionally substituted C １－６ The compound according to claim 1, wherein the substituent is selected from the group consisting of an alkanoyl group, and the other symbols are the same as those defined for partial structural formula (V) in claim 1.

3. R ​​is (1) a partial structural formula (II): (Wherein, w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl group, 3) C ３－８ 4) a halogen atom and C ３－８ C, which may be substituted with 1 to 3 identical or different groups selected from cycloalkyl groups; １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) halogen atom, cyano group, C １－６ Alkyl group and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryloxy group, 7) halogen atom and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ (2) a group represented by partial structural formula (III): (Wherein, x R ｂ are present on the same or different constituent atoms of ring B, each independently representing: 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl group, 3) C ３－８ 4) a halogen atom and C ３－８ C, which may be substituted with 1 to 3 identical or different groups selected from cycloalkyl groups; １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) halogen atom, cyano group, C １－６ Alkyl group and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryloxy group, 7) halogen atom and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ (3) a group represented by partial structural formula (IV): (Wherein, y R ｃ are present on the same or different constituent atoms of ring C, each independently representing: 1) a halogen atom, 2) a C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl group, 3) C ３－８ 4) a halogen atom and C ３－８ C, which may be substituted with 1 to 3 identical or different groups selected from cycloalkyl groups; １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) halogen atom, cyano group, C １－６ Alkyl group and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryloxy group, 7) halogen atom and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ (4) a group represented by partial structural formula (V): (Wherein, z R ｄ are present on the same or different constituent atoms of ring D, each independently representing: 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl group, 3) C ３－８ 4) a halogen atom and C ３－８ C, which may be substituted with 1 to 3 identical or different groups selected from cycloalkyl groups; １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) halogen atom, cyano group, C １－６ Alkyl group and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryloxy group, 7) halogen atom and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ The compound according to claim 1 or a salt thereof, wherein the substituent is selected from the group consisting of an alkanoyl group, and an alkanoyl group, and the other symbols are the same as those defined for partial structural formula (V) in claim 1.

4. R is (1) a partial structural formula (II): (Wherein, ring A is 1) a 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocycle containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl group, 3) C ３－８ 4) a halogen atom and C ３－８ C, which may be substituted with 1 to 3 identical or different groups selected from cycloalkyl groups; １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) halogen atom, cyano group, C １－６ Alkyl groups, and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryloxy group, 7) halogen atom and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryl group, 8) a 5- to 14-membered aromatic heterocycle-oxy group, and 9) C １－６ an alkanoyl group; and w is an integer from 0 to 3; is a bond, and * is the bonding position to the methylene group; (2) a group represented by partial structural formula (III): (Wherein, ring A is a 4-6 membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６ a cycloalkane, where ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3; is a bond, and * is the bonding position to the methylene group; (3) a group represented by partial structural formula (IV): (Wherein, ring C is C ３－１０ Cycloalkane or C ６－１０ an aromatic carbocyclic ring, ｃ are present on the same or different constituent atoms of ring C, and each independently represents １－６ an alkyl group, y is an integer from 0 to 3, is a bond, * is the position of attachment to a methylene group, L １ is C １－６ represents an alkylene group, and n is 0 or 1; or (4) a group represented by partial structural formula (V): (Wherein, ring C is C ３－６ A cycloalkane, wherein ring D is C ３－６ cycloalkane, where Ring D is spiro-bonded to Ring C to form a bicyclic ring, z is an integer equal to 0, is a bond, * is the position of attachment to a methylene group, L ２ is C １－６ The compound according to claim 1 , wherein R is an alkylene group, and n is 0 or 1.

5. R is a group represented by partial structural formula (II): (Wherein, ring A is 1) a 6-membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom and further containing one silicon atom as a ring-constituting atom, or 2) a 6-membered nitrogen-containing saturated heterocycle containing 1 to 2 nitrogen atoms as ring-constituting atoms, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) a halogen atom, 2) C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl group, 3) C ３－８ 4) a halogen atom and C ３－８ C, which may be substituted with 1 to 3 identical or different groups selected from cycloalkyl groups; １－６ alkoxy group, 5) C ３－８ cycloalkyloxy group, 6) halogen atom, cyano group, C １－６ Alkyl groups, and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryloxy group, 7) halogen atom and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ aryl group, 8) 5- to 14-membered aromatic heterocycle-oxy group (preferably a 5- to 6-membered nitrogen-containing aromatic heterocycle-oxy group containing 1 to 3 nitrogen atoms as ring-constituting atoms), and 9) C １－６ an alkanoyl group; and w is an integer from 0 to 3; is a bond, and * is a bonding position to a methylene group. The compound or salt thereof according to any one of claims 1 to 4, 6. Ring A is an azasilinane and has w R ａ are present on the same or different constituent atoms of ring A, and each independently represents １－６ ring A is piperidine, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents 1) C １－６ 2) an alkyl group, ３－８ C, which may be substituted with 1 to 3 identical or different groups selected from cycloalkyl groups; １－６ alkoxy group, 3) halogen atom, cyano group, C １－６ Alkyl groups, and C １－６ C may be substituted with 1 to 3 identical or different groups selected from alkoxy groups. ６－１４ 4) an aryloxy group, or 5) an aromatic heterocycle-oxy group, or Ring A is piperazine, and w R ａ are present on the same or different constituent atoms of ring A, and each independently represents １－６ The compound or salt thereof according to claim 5 , which is an alkanoyl group.

7. N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-tert-butoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide, N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-toluyloxy)piperidin-1-yl]methyl}phenyl)acetamide, or an acid addition salt thereof. The compound or salt thereof according to any one of claims 1 to 4.

8. R is a compound represented by the partial structural formula (III): (Wherein, ring A is a 4-6 membered nitrogen-containing saturated heterocycle containing one nitrogen atom as a ring-constituting atom, and ring B is C ３－６ a cycloalkane, where ring B is spiro-bonded to ring A or fused to ring A to form a bicyclic ring, and x R ｂ are present on the same or different constituent atoms of ring B, and each independently represents a halogen atom; x is an integer of 0 to 3; is a bond, and * is a bonding position to a methylene group. The compound or salt thereof according to any one of claims 1 to 4, 9. R is a compound represented by the partial structural formula (III):

9. The compound according to claim 8, or a salt thereof, wherein ring A is azetidine or piperidine, and ring B is cyclopropane, cyclobutane, or cyclohexane, where ring B is spiro-bonded to ring A to form a bicyclic ring.

10. N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(6-azaspiro[2.5]octan-6-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, The compound or salt thereof according to any one of claims 1 to 4, which is 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, 4-(2-azaspiro[3.5]nonan-2-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, or an acid addition salt thereof.

11. R is a compound represented by the partial formula (IV): (Wherein, ring C is C ３－１０ Cycloalkane or C ６－１０ an aromatic carbocyclic ring, ｃ are present on the same or different constituent atoms of ring C, and each independently represents １－６ an alkyl group, y is an integer from 0 to 3, is a bond, * is the position of attachment to a methylene group, L １ is C １－６ The compound or salt thereof according to any one of claims 1 to 4, wherein R is an alkylene group, and n is 0 or 1.

12. The compound or salt thereof according to claim 11, wherein Ring C is cyclohexane, adamantane, or benzene.

13. The compound or salt thereof according to any one of claims 1 to 4, which is 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(2-phenylpropan-2-ylamino)methyl]phenyl}acetamide, or an acid addition salt thereof.

14. R is a group represented by partial structural formula (V): (Wherein, ring C is C ３－６ A cycloalkane, wherein ring D is C ３－６ cycloalkane, where Ring D is spiro-bonded to Ring C to form a bicyclic ring, z is an integer equal to 0, is a bond, * is the position of attachment to a methylene group, L ２ is C １－６ The compound or salt thereof according to any one of claims 1 to 4, wherein R is an alkylene group, and n is 0 or 1.

15. The compound or salt thereof according to claim 14, wherein ring C and ring D are cyclohexane, where ring D is spiro-bonded to ring C to form a bicyclic ring, and n is 0.

16. The compound or salt thereof according to any one of claims 1 to 4, which is 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, or an acid addition salt thereof.

17. N-{4-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropylpiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, N-[4-(2-azaspiro[3.5]nonan-2-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(6-azaspiro[2.5]octan-6-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-tert-butylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-cyclohexylpiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4-cyclopropylpiperazin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-neopentylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(difluoromethyl)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(trans-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(cis-octahydroquinolin-1(2H)-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-tert-butoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isobutoxypiperidin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(cyclohexyloxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(cyclohexylmethoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-methoxy-4-methylpiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-phenoxypiperidin-1-yl)methyl]phenyl}acetamide, N-{4-[(4-cyclopropoxypiperidin-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-ethoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-propoxypiperidin-1-yl)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(trifluoromethoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(3-methoxyphenyl)piperazin-1-yl]methyl}phenyl)acetamide, N-(4-{[4-(2-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(cyclohexylmethylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(2-adamantylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(4,4-dimethylcyclohexylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-{4-[(benzylamino)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(2-phenylpropan-2-ylamino)methyl]phenyl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N{4-[(4-pivaloylpiperazin-1-yl)methyl]phenyl}acetamide, N-(4-{[4-(2-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-(4-{[4-(4-cyanophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(4-fluorophenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-3-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(pyridin-4-yloxy)piperidin-1-yl]methyl}phenyl)acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(2-methoxyphenoxy)piperidin-1-yl]methyl}phenyl)acetamide, 4-(3-azaspiro[5.5]undecan-3-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, 4-(2-azaspiro[3.5]nonan-2-ylmethyl)-N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)benzamide, N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(4-isopropylpiperidin-1-yl)methyl]benzamide, The compound according to claim 1, which is N-(4-{[4-(4-chlorophenoxy)piperidin-1-yl]methyl}phenyl)-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-(4-{[4-(p-toluyloxy)piperidin-1-yl]methyl}phenyl)acetamide, or an acid addition salt thereof, or a salt thereof.

18. N-{4-[(4,4-dimethyl-1,4-azasilinan-1-yl)methyl]phenyl}-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(4-isopropoxypiperidin-1-yl)methyl]phenyl}acetamide, N-[4-(3-azaspiro[5.5]undecan-3-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, N-[4-(7-azaspiro[3.5]nonan-7-ylmethyl)phenyl]-2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}acetamide, 2-{4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}-N-{4-[(spiro[5.5]undecan-3-ylamino)methyl]phenyl}acetamide, The compound or salt thereof according to claim 1, which is N-({4-[1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl]thiophen-2-yl}methyl)-4-[(spiro[5.5]undecan-3-ylamino)methyl]benzamide, or an acid addition salt thereof.

19. The compound or salt thereof according to any one of claims 1 to 4, wherein L is a group represented by the formula: -NH-CO-.

20. The compound or salt thereof according to any one of claims 1 to 4, wherein L is a group represented by the formula: -CO-NH-.

21. A medicine comprising the compound or salt thereof according to any one of claims 1 to 4 as an active ingredient.

22. The pharmaceutical agent according to claim 21, which is an inhibitor of the proliferation of hematopoietic tumor cells.

23. The pharmaceutical agent according to claim 22, which is a preventive or therapeutic agent for blood cancer.

24. The pharmaceutical composition according to claim 23, wherein the blood cancer is leukemia, malignant lymphoma, or multiple myeloma.

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