Substitutive phenyl-1H-pyrrolo[2,3-c]pyridine derivatives

Abstract

The present invention relates to medicaments useful for the treatment and / or prevention in mammals, pharmaceutical compositions comprising such compounds, and their use as menin / MLL protein / protein interaction inhibitors useful in the treatment of diseases such as cancer, including but not limited to leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN); and diabetes.

Description

[Technical Field]

[0001] The present invention relates to pharmaceuticals useful for the treatment and / or prevention in mammals, pharmaceutical compositions comprising such compounds, and their use as menin / MLL protein / protein interaction inhibitors useful for the treatment of diseases including, but not limited to, leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN); and diabetes. [Background technology]

[0002] Chromosomal rearrangements affecting mixed lineage leukemia (MLL; MLL1; KMT2A) cause invasive acute leukemia across all age groups, remaining largely incurable, which highlights the urgent need for novel therapeutic approaches. Acute leukemia with these MLL chromosomal translocations can be lymphoid, myeloid, or dimorphic, accounting for 5-10% of acute leukemia in adults and approximately 70% in infants (Marschalek, Br J Haematol 2011.152(2),141-54; Tomizawa et al., Pediatr Blood Cancer 2007.49(2),127-32).

[0003] MLL is a histone methyltransferase that methylates histone H3 (H3K4) at lysine 4 and functions within a multiprotein complex. The use of the inducible loss-of-function allele of Mll1 demonstrated that Mll1 plays a crucial role in the maintenance of hematopoietic stem cells (HSCs) and B cell development, but its histone methyltransferase activity is not required for hematopoiesis (Mishra et al., Cell Rep 2014.7(4),1239-47).

[0004] Fusions of MLL with over 60 different partners have been reported to date and have been associated with leukemia formation / progression (Meyer et al., Leukemia 2013.27, 2165-2176). Interestingly, the SET (Su(var)3-9, zeste enhancer, and trithorax) domains of MLL are not retained in the chimeric protein but are replaced by the fusion partner (Thiel et al., Bioessays 2012.34, 771-80). When chromatin-modifying enzymes such as the Dot1L and / or pTEFb complex are recruited by the fusion partner, transcription and transcriptional elongation of MLL target genes, most notably the HOXA gene (e.g., HOXA9) and the HOX cofactor MEIS1, are enhanced. Subsequently, the abnormal expression of these genes inhibits hematopoietic differentiation and enhances proliferation.

[0005] Menin, encoded by the Multiple Endocrine Neoplasia type 1 (MEN1) gene, is ubiquitously expressed and primarily localized in the nucleus. It interacts with numerous proteins and has therefore been shown to be involved in a variety of cellular processes. Menin's best-understood function is its role as an oncogenic cofactor for MLL fusion proteins. Menin interacts with MBM1 (menin-binding motif 1) and MBM2, two motifs within the N-terminal fragment of MLL that are retained in all fusion proteins (Thiel et al., Bioessays 2012.34, 771-80). The menin / MLL interaction creates a new interaction surface for lens epithelium-derived growth factor (LEDGF). While MLL directly binds to LEDGF, menin is essential for stable interaction between MLL and LEDGF, and for gene-specific chromatin recruitment of the MLL complex via the PWWP domain of LEDGF (Cermakova et al., Cancer Res 2014.15, 5139-51; Yokoyama & Cleary, Cancer Cell 2008.8, 36-46). Furthermore, numerous genetic studies have shown that menin is strictly required for oncogenic transformation by MLL fusion proteins, suggesting that the menin / MLL interaction is an attractive therapeutic target. For example, conditional deletion of Men1 inhibits leukocytosis in myeloid progenitor cells ectopically expressing MLL fusions (Chen et al., Proc Natl Acad Sci 2006.103, 1018-23). Similarly, genetic disruption of the menin / MLL fusion interaction by loss-of-function mutations neutralizes the oncogenic properties of the MLL fusion protein, preventing the development of leukemia in vivo and releasing the inhibition of differentiation of MLL-transformed leukemic blasts. These studies also demonstrated that menin is necessary for maintaining HOX gene expression by the MLL fusion protein (Yokoyama et al., Cell 2005.123,207-18).In addition, small molecule inhibitors of the menin / MLL interaction have been developed, suggesting the drug potential of this protein / protein interaction and demonstrating its efficacy in preclinical models of AML (Borkin et al., Cancer Cell 2015.27, 589-602; Cierpicki and Grembecka, Future Med Chem 2014.6, 447-462). Combined with the finding that menin is not an essential cofactor of MLL1 in normal hematopoiesis (Li et al., Blood 2013.122, 2039-2046), these data demonstrate that disrupting the menin / MLL interaction is a promising new therapeutic approach for treating MLL rearrangement leukemia and other cancers with an active HOX / MEIS1 gene signature. For example, intragenetic partial tandem duplication (PTD) within the 5' region of the MLL gene represents another major abnormality primarily seen in novel and secondary AML and myelodysplastic syndromes. Although the molecular mechanisms and biological functions of MLL-PTD are not fully understood, novel therapeutic targeting strategies that affect menin / MLL interactions may prove effective in treating MLL-PTD-associated leukemia. Furthermore, castration-resistant prostate cancer has been shown to be dependent on menin / MLL interactions (Malik et al., Nat Med 2015.21, 344-52).

[0006] The MLL protein is also known in the scientific field as the histone-lysine N-methyltransferase 2A (KMT2A) protein (UniProt acceptance number Q03164).

[0007] Several references describe inhibitors targeting the menin-MLL interaction: International Publication No. 2011 / 029054, J Med Chem 2016, 59, 892-913 describes the preparation of thienopyrimidine and benzodiazepine derivatives; International Publication No. 2014 / 164543 describes thienopyrimidine and thienopyridine derivatives; Nature Chemical Biology March 2012, 8, 277-284 and Ren, J.; et al. Bioorg Med Chem Lett (2016), 26(18), 4472-4476 describes thienopyrimidine derivatives; J Med Chem 2014, 57, 1543-1556 describes hydroxy and aminomethylpiperidine derivatives; Med Chem 2014,6,447-462 provides an overview of small molecules and peptide mimetic compounds, and International Publication No. 2016 / 195776 describes flu[2,3-d]pyrimidine, 9H-purine, [1,3]oxazolo[5,4-d]pyrimidine, [1,3]oxazolo[4,5-d]pyrimidine, [1,3]thiazolo[5,4-d]pyrimidine, thieno[2,3-b]pyridine, and thieno[2,3-d]pyrimidine. Limidine derivatives are described, and International Publication No. 2016 / 197027 describes 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine, 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine, pyrido[2,3-d]pyrimidine, and quinoline derivatives, while International Publication No. 2016 / 040330 describes thienopyrimidine and thienopyridine compounds. International Publication No. 2017 / 192543 describes piperidine as a menin inhibitor. International Publications 2017 / 112768, 2017 / 207387, 2017 / 214367, 2018 / 053267, and 2018 / 024602 describe inhibitors of menin-MLL interaction. International Publications 2017 / 161002 and 2017 / 161028 describe inhibitors of menin-MLL.International Publications 2018 / 050686, 2018 / 050684, and 2018 / 109088 describe inhibitors of menin-MLL interaction. International Publication 2018 / 226976 describes methods and compositions for inhibiting the interaction between menin and MLL protein. International Publication 2018 / 175746 provides methods for the treatment of hematological malignancies and Ewing's sarcoma. International Publications 2018 / 106818 and 2018 / 106820 provide methods for promoting the proliferation of pancreatic cells. International Publication 2018 / 153312 discloses azaspiro compounds in the field of medicinal chemistry. International Publication No. 2017 / 132398 discloses a method involving contacting leukemia cells exhibiting an NPM1 mutation with a pharmacological inhibitor of the interaction between MLL and menin. International Publication No. 2019 / 060365 describes menin-MLL substitution inhibitors. International Publication No. 2020 / 069027 describes the treatment of hematological malignancies with menin inhibitors. Krivtsov et al., Cancer Cell 2019. No.6 Vol.36, 660-673, describes menin-MLL inhibitors.

[0008] International Publication No. 2014 / 199171 discloses a compound as a VAP1 inhibitor. International Publication Nos. 2011 / 113798 and 2013 / 037411 disclose a compound as an SSAO inhibitor. International Publication No. 2011 / 056440 discloses a compound as a CCR1 inhibitor.

[0009] International Publication No. 2021 / 060453 describes cross-linked optically active secondary amine derivatives. International Publication No. 2021 / 121327 describes substituted linear spiro derivatives and their use as menin / MLL protein / protein interaction inhibitors. [Overview of the project]

[0010] The present invention relates to formula (I)

[0011] [Chemical formula] [wherein, Q is -CHR y -, -O-, -C(=O)-, -NR q -, or -CR y =, the dotted line is an optional additional bond for forming a double bond when Q represents -CR y =, R 1a is hydrogen, cyano, halo, Het, -C(=O)-NR xa R xb , -S(=O)2-R 18 , -C(=O)-O-C 1~4 alkyl-NR 22a R 22b , -C(=O)-O-C 1~4 alkyl,

[0012] [Chemical formula] represents, R 18 is C 1~6 alkyl or C 3~6 cycloalkyl, R 19 is hydrogen or C 1~6 alkyl, or [[ID=5�]] R 18 and R 19 together form -(CH2)3-, -(CH2)4-, or -(CH2)5-, Het is a monocyclic 5- or 6-membered aromatic ring containing 1, 2, or 3 O-, S-, or N-atoms and optionally a carbonyl moiety (wherein the monocyclic 5- or 6-membered aromatic ring is optionally substituted with 1, 2, or 3 substituents selected from the group consisting of C 1~4 alkyl, C 3~6 cycloalkyl, or cyano), R xa and R xb are each independently hydrogen, Het 3 , C 3~6 cycloalkyl, and C1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl, -C 1~4 alkyl-OH, halo, CF3, C 3~6 Cycloalkyl, Het 3 , and NR 11c R 11d (Substituted with 1, 2, or 3 substituents selected from the group consisting of, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, cyano, halo, and OR 23 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, cyano, and each independently halo and OR 23 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups) R23 However, C is substituted with hydrogen or, optionally, one, two, or three halos. 1~4 Represents alkyl, R 1b However, hydrogen, F, Cl, or -OC 1~4 Represents alkyl, R 2 But, hello, C 3~6 Cycloalkyl, C 1~4 Alkyl, -OC 1~4 C substituted with alkyl, cyano, or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3a This represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each is independent, covalently bonded or

[0013] [ka] This represents, n1 is selected from 1 and 2. n2 is selected from 1, 2, 3, and 4. R y However, hydrogen, -OH, C 1~4 Alkyl, -C 1~4 Alkyl-OH, or -C 1~4 Alkyl-OC 1~4 Represents alkyl, R q However, hydrogen or C 1~4 Represents alkyl, R 5 However, hydrogen, C 1~4 Alkyl, or C 3~6 Represents cycloalkyl, R 3 , R 3a , and R 4each independently being Het 1 ; Het 2 ; Cy 2 ; C 1~8 alkyl; and each independently -C(=O)-NR 10a R 10b 、-C(=O)-Het 6a 、-C(=O)-Het 6b 、-NR 10c -C(=O)-C 1~4 alkyl, -S(=O)2-C 1~4 alkyl, -NR xc R xd 、-NR 8a R 8b 、-CF3, cyano, halo, -OH, -O-C 1~4 alkyl, Het 1 、Het 2 、Ar 1 、and Cy 2 selected from the group consisting of 1, 2, 3, or 4 substituents selected from the group consisting of C 1~8 alkyl, R xc being Cy 1 、Het 5 、-C 1~6 alkyl-Cy 1 、-C 1~6 alkyl-Het 3 、-C 1~6 alkyl-Het 4 、or -C 1~6 alkyl-phenyl, R xd being hydrogen; C 1~4 alkyl; or C 1~4 alkyl substituted with 1, 2, or 3 substituents selected from the group consisting of halo, -OH, -O-C 1~4 alkyl, and cyano, or R xc and R xdThese combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl-S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl;-(C=O)-C 1~4 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4 Alkyl, -C(=O)-NR 10a R 10b , and -NR 10c -C(=O)-C 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 1~6 Selected from the group consisting of alkyl groups, Ar 1 However, each can be chosen independently of C 1~4 alkyl, halo, -OC 1~4Alkyl, -CF3, -OH, -S(=O)2-C 1~4 Alkyl and -C(=O)-NR 10a R 10b Represents phenyl substituted with 1, 2, or 3 substituents selected from the group consisting of the following: Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH. , Het 2 However, this represents a C-bonded pyrazolyl, 1,2,4-oxadiazolyl, pyridazinyl, or triazolyl, and this can be optionally configured with R on one nitrogen atom. 6a It may be replaced with, R 6 and R 6a However, each is independent, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-C(=O)-Het 6a ;-C(=O)-NR 10d R 10e;-C(=O)-OC 1~4 Alkyl;-S(=O)2-C 1~4 Alkyl; each can be selected independently and Het 3 , Het 4 , Het 6a , Het 6b Cy 1 -CN, -OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-N(C 1~4 Alkyl)2,-C(=O)-NH-C 1~4 Alkyl-C 3~6 Cycloalkyl, -C(=O)-OH, -NR 11a R 11b , and -NH-S(=O)2-C 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 1~6 Alkyl; and optionally, -CN, -OH, -OC, each independently. 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-N(C 1~4 Alkyl)2,-NH-S(=O)2-C 1~4 Alkyl, and optionally OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl and -NH-S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 3~6 Selected from the group consisting of cycloalkyl groups, R 8 However, hydrogen, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, Halo, Cyano, -NR 11a R 11b -S(=O)2-C 1~4 Alkyl, Het 3a , and Het 6a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 , Het 3a , Het 5 , and Het 5a However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline may optionally have a carbon atom on one carbon atom, C 1~4 Alkyl, halo, -OH, -NR 11a R 11b , or substituted with an oxo, and the heterocyclyl optionally has a C on one nitrogen atom. 1~4 Alkyl or -(C=O)-C 1~4 Substituted with alkyl , Het 4 and Het 7 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring, or each may independently contain one, two, three, or four heteroatoms selected from O, S, and N in a fused bicyclic carbon bond 9 or 10-membered aromatic ring (in which case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 Alkyl or -(C=O)-OC 1~4 The aromatic ring is substituted, and optionally, on one or two carbon atoms, each independently, -OH, halo, C 1~4 Alkyl, -OC 1~4 Alkyl, -NR 11a R 11b , C 1~4 Alkyl-NR 11a R 11b -NH-C(=O)-C 1~4 Alkyl, cyano, -COOH, -NH-C(=O)-OC 1~4Alkyl, -NH-C(=O)-Cy 3 -NH-C(=O)-NR 10a R 10b -(C=O)-OC 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, Het 8a , -C 1~4 Alkyl-Het 8a , Het 8b , Het 9 , and -C(=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a , Het 8 , and Het 8a However, each contains independently one N atom and optionally, each independently selected from O, S, and N, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have, on one or two carbon atoms, each independently, a halo, -OH, oxo, or -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 -(C=O)-NR 10a R 10b ,-OC 3~6 Cycloalkyl, -S(=O)2-C 1~4 Alkyl, cyano, C 1~4 Alkyl, -C 1~4 alkyl-OH, -OC 1~4 Alkyl, -O-(C=O)-NR 10a R 10b , and -O-(C=O)-C 1~4 The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by a substituent selected from the group consisting of) Het6b and Het 8b However, each contains independently one N atom and optionally, independently, one or two additional heteroatoms selected from O, S, and N, forming a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have one or two carbon atoms independently of each other C 1~4 Alkyl, -OH, oxo, -(C=O)-NR 10a R 10b -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 , and -OC 1~4 The heterocyclyl is substituted with a total of one or two substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -C(=O)-Cy 3 -(C=O)-C 1~4 alkyl-OH, -C(=O)-C 1~4 Alkyl-OC 1~4 Alkyl, -C(=O)-C 1~4 Alkyl-NR 11a R 11b , and C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 9 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 The alkyl group is substituted, and the aromatic ring may optionally have -OH, halo, and C on one or two carbon atoms, each independently. 1~4 (Represents a group consisting of alkyl groups, which consists of a total of one or two substituents selected from the group,) Cy 1 However, at the discretion of choice, -OH, -NH-C(=O)-C 1~4 Alkyl, C 1~4Alkyl, -NH-S(=O)2-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, C 1~4 Alkyl, -OC 1~4 Alkyl, cyano,

[0014] [ka] Furthermore, each independently of Het 3a , Het 6a , Het 6b , and -NR 9a R 9b C substituted with one or two substituents selected from the group consisting of 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) Cy 3 However, C 3~7 Cycloalkyl (in this case, the C 3~7 This represents a cycloalkyl group that is optionally substituted with one, two, or three halo substituents. R 9a and R 9b However, each independently, hydrogen;C 1~4 Alkyl; C 3~6 Cycloalkyl;-C(=O)-C 1~4 Alkyl;-C(=O)-C 3~6 Cycloalkyl;-S(=O)2-C 1~4 Alkyl; Het 5 ;Het 7;-C 1~4 Alkyl-R 16 ;-C(=O)-C 1~4 Alkyl-Het 3a ;-C(=O)-R 14 ; Hal, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 3~6 Cycloalkyl; as well as halo, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 1~4 Selected from the group consisting of alkyl groups, R 11a , R 11b , R 13a , R 13b , R 15a , R 15b , R 17a , R 17b , R 20a , R 20b , R 22a , and R 22b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 11c and R 11d However, each independently, hydrogen, C 1~6 Alkyl and -C(=O)-C 1~4 Selected from the group consisting of alkyl groups, R 10a , R 10b , and R 10c However, each independently, hydrogen, C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 10d and R 10e However, each is independent, C 1~4 Alkyl, -OC 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 14 However, Het 5a ;Het7 ;Het 8a ;-OC 1~4 Alkyl;-C(=O)NR 15a R 15b ;-OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halo 3~6 Cycloalkyl; or -OC 1~4 Alkyl, -NR 13a R 13b , halo, cyano, -OH, het 8a , and Cy 1 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 Represents alkyl, R 16 However, -C(=O)-NR 17a R 17b -S(=O)2-C 1~4 Alkyl, Het 5 , Het 7 , or Het 8 [represents] This invention relates to novel compounds of, as well as their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0015] Substituent R in formula (I) 21 and -YR 3 It should be clear that these substituents can bond to any carbon or nitrogen atom in the ring they are bonded to, thereby replacing a hydrogen atom on the same atom or a hydrogen atom on a different atom (including a nitrogen atom) in that portion. Lines drawn from substituents into the ring system indicate that the bond can be to any of the preferred ring atoms.

[0016] The present invention relates to formula (A)

[0017] [ka] [In the formula, L is either absent or represents -CH2- or -CH2-CH2-, Q is -CHR y-, -O-, -C(=O)-, -NR q -, or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, cyano, halo, het, -C(=O)-NR xa R xb -S(=O)2-R 18 -C(=O)-OC 1~4 Alkyl-NR 22a R 22b -C(=O)-OC 1~4 Alkyl,

[0018] [ka] This represents, R 18 However, C 1~6 Alkyl or C 3~6 Represents cycloalkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, or R 18 and R 19 They combine to form -(CH2)3-, -(CH2)4-, or -(CH2)5-, Het is a monocyclic 5 or 6-membered aromatic ring containing 1, 2, or 3 O-, S-, or N- atoms and optionally a carbonyl moiety (in this case, the monocyclic 5 or 6-membered aromatic ring optionally contains C 1~4 Alkyl, C 3~6 (represented by being substituted with one, two, or three substituents selected from the group consisting of cycloalkyl, halo, or cyano) R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6 Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4Alkyl, -C 1~4 alkyl-OH, halo, CF3, C 3~6 Cycloalkyl, Het 3 , and NR 11c R 11d (Substituted with 1, 2, or 3 substituents selected from the group consisting of, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, cyano, halo, and OR 23 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xb Together, they form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, along with the N atom to which they bond (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, cyano, and each independently halo and OR 23 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), R 23 However, C is substituted with hydrogen or, optionally, one, two, or three halos. 1~4 Represents alkyl, R 1b However, hydrogen, F, Cl, or -OC1~4 Represents alkyl, R 2 But, hello, C 3~6 Cycloalkyl, C 1~4 Alkyl, -OC 1~4 C substituted with alkyl, cyano, or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 2a However, hydrogen or C 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3a This represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each is independent, covalently bonded or

[0019] [ka] This represents, n3 is selected from 0 and 1. n4 is selected from 0, 1, 2, and 3. R y However, hydrogen, -OH, C 1~4 Alkyl, -C 1~4 Alkyl-OH, or -C 1~4 Alkyl-OC 1~4 Represents alkyl, R q However, hydrogen or C 1~4 Represents alkyl, R 5 However, hydrogen, C 1~4 Alkyl, or C 3~6 Represents cycloalkyl, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C1~8 Alkyl; and each independently -C(=O)-NR 10a R 10b -C(=O)-Het 6a -C(=O)-Het 6b , -NR 10c -C(=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, cyano, halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 Ar 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8 Selected from the group consisting of alkyl groups, R xc However, Cy 1 , Het 5 , -C 1~6 Alkyl-Cy 1 , -C 1~6 Alkyl-Het 3 , -C 1~6 Alkyl-Het 4 , or -C 1~6 Represents alkylphenyl, R xd However, hydrogen; C 1~4 alkyl; or halo, -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano 1~4 Represents alkyl, or R xc and R xd These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4Alkyl, -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl-S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl;-(C=O)-C 1~4 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4 Alkyl, -C(=O)-NR 10a R 10b , and -NR 10c -C(=O)-C 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 1~6 Selected from the group consisting of alkyl groups, Ar 1 However, each can be chosen independently of C 1~4 alkyl, halo, -OC 1~4 Alkyl, -CF3, -OH, -S(=O)2-C 1~4 Alkyl and -C(=O)-NR 10a R 10b Represents phenyl substituted with one, two, or three substituents selected from the group consisting of the following: Het 1However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH. , Het 2 However, this represents a C-bonded pyrazolyl, 1,2,4-oxadiazolyl, pyridazinyl, or triazolyl, and this can be optionally configured with R on one nitrogen atom. 6a It may be replaced with, R 6 and R 6a However, each is independent, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-C(=O)-Het 6a ;-C(=O)-NR 10d R 10e ;-C(=O)-OC 1~4 Alkyl;-S(=O)2-C 1~4 Alkyl; optional, each independently Het 3 , Het 4 , Het 6a , Het 6b Cy 1-CN, -OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-N(C 1~4 Alkyl)2,-C(=O)-NH-C 1~4 Alkyl-C 3~6 Cycloalkyl, -C(=O)-OH, -NR 11a R 11b , and -NH-S(=O)2-C 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 1~6 Alkyl; and optionally, -CN, -OH, -OC, each independently. 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-N(C 1~4 Alkyl)2,-NH-S(=O)2-C 1~4 Alkyl, and optionally OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl and -NH-S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 3~6 Selected from the group consisting of cycloalkyl groups, R 8 However, hydrogen, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, Halo, Cyano, -NR 11a R 11b -S(=O)2-C 1~4 Alkyl, Het 3a , and Het 6a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 , Het 3a , Het 5 , and Het 5aHowever, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline may optionally have a carbon atom on one carbon atom, C 1~4 Alkyl, halo, -OH, -NR 11a R 11b , or substituted with an oxo, and the heterocyclyl optionally has a C on one nitrogen atom. 1~4 Alkyl or -(C=O)-C 1~4 Substituted with alkyl , Het 4 and Het 7 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring, or each may independently contain one, two, three, or four heteroatoms selected from O, S, and N in a fused bicyclic carbon bond 9 or 10-membered aromatic ring (in which case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 Alkyl or -(C=O)-OC 1~4 The aromatic ring is substituted, and optionally, on one or two carbon atoms, each independently, -OH, halo, C 1~4 Alkyl, -OC 1~4 Alkyl, -NR 11a R 11b , C 1~4 Alkyl-NR 11a R 11b -NH-C(=O)-C 1~4 Alkyl, cyano, -COOH, -NH-C(=O)-OC 1~4 Alkyl, -NH-C(=O)-Cy 3 -NH-C(=O)-NR 10a R 10b -(C=O)-OC 1~4Alkyl, -NH-S(=O)2-C 1~4 Alkyl, Het 8a , -C 1~4 Alkyl-Het 8a , Het 8b , Het 9 , and -C(=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a , Het 8 , and Het 8a However, each contains independently one N atom and optionally, each independently selected from O, S, and N, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have, on one or two carbon atoms, each independently, a halo, -OH, oxo, or -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 -(C=O)-NR 10a R 10b ,-OC 3~6 Cycloalkyl, -S(=O)2-C 1~4 Alkyl, cyano, C 1~4 Alkyl, -C 1~4 alkyl-OH, -OC 1~4 Alkyl, -O-(C=O)-NR 10a R 10b , and -O-(C=O)-C 1~4 The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by a substituent selected from the group consisting of) Het 6b and Het 8bHowever, each contains independently one N atom and optionally, independently, one or two additional heteroatoms selected from O, S, and N, forming a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have one or two carbon atoms independently of each other C 1~4 Alkyl, -OH, oxo, -(C=O)-NR 10a R 10b -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 , and -OC 1~4 The heterocyclyl is substituted with a total of one or two substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -C(=O)-Cy 3 -(C=O)-C 1~4 alkyl-OH, -C(=O)-C 1~4 Alkyl-OC 1~4 Alkyl, -C(=O)-C 1~4 Alkyl-NR 11a R 11b , and C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 9 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 The alkyl group is substituted, and the aromatic ring may optionally have -OH, halo, and C on one or two carbon atoms, each independently. 1~4 (Represents a group consisting of alkyl groups, which consists of a total of one or two substituents selected from the group,) Cy 1 However, at the discretion of choice, -OH, -NH-C(=O)-C 1~4 Alkyl, C 1~4 Alkyl, -NH-S(=O)2-C 1~4Alkyl, -S(=O)2-C 1~4 Alkyl and -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, C 1~4 Alkyl, -OC 1~4 Alkyl, cyano,

[0020] [ka] Furthermore, each independently of Het 3a , Het 6a , Het 6b , and -NR 9a R 9b C substituted with one or two substituents selected from the group consisting of 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) Cy 3 However, C 3~7 Cycloalkyl (in this case, the C 3~7 This represents a cycloalkyl group that is optionally substituted with one, two, or three halo substituents. R 9a and R 9b However, each independently, hydrogen;C 1~4 Alkyl; C 3~6 Cycloalkyl;-C(=O)-C 1~4 Alkyl;-C(=O)-C 3~6 Cycloalkyl;-S(=O)2-C 1~4 Alkyl; Het 5 ;Het 7 ;-C 1~4 Alkyl-R16 ;-C(=O)-C 1~4 Alkyl-Het 3a ;-C(=O)-R 14 ; Hal, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 3~6 Cycloalkyl; as well as halo, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 1~4 Selected from the group consisting of alkyl groups, R 11a , R 11b , R 13a , R 13b , R 15a , R 15b , R 17a , R 17b , R 20a , R 20b , R 22a , and R 22b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 11c and R 11d However, each independently, hydrogen, C 1~6 Alkyl and -C(=O)-C 1~4 Selected from the group consisting of alkyl groups, R 10a , R 10b , and R 10c These are, independently, hydrogen and C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 10d and R 10e However, each is independent, C 1~4 Alkyl, -OC 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 14 However, Het 5a ;Het 7 ;Het8a ;-OC 1~4 Alkyl;-C(=O)NR 15a R 15b ;-OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halo 3~6 Cycloalkyl; or -OC 1~4 Alkyl, -NR 13a R 13b , halo, cyano, -OH, het 8a , and Cy 1 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 Represents alkyl, R 16 However, -C(=O)-NR 17a R 17b -S(=O)2-C 1~4 Alkyl, Het 5 , Het 7 , or Het 8 This represents, R 24 However, hydrogen or C 1~4 [Represents alkyl] The present invention relates to novel compounds thereof, as well as their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0021] Substituent R in formula (A) 21 , R 24 , and -YR 3 It should be clear that these substituents can bond to any carbon or nitrogen atom in the ring they are bonded to, thereby replacing a hydrogen atom on the same atom or a hydrogen atom on a different atom (including a nitrogen atom) in that portion. Lines drawn from substituents into the ring system indicate that the bond can be to any of the preferred ring atoms.

[0022] The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

[0023] The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier or excipient.

[0024] Furthermore, the present invention relates to compounds of formula (I), pharmaceutically acceptable salts thereof, or pharmaceutically acceptable solvates thereof for use as pharmaceuticals, including but not limited to cancers such as leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN); and also to compounds of formula (I), pharmaceutically acceptable salts thereof, or pharmaceutically acceptable solvates thereof for use in the treatment or prevention of diabetes.

[0025] In certain embodiments, the present invention relates to a compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof for use in the treatment or prevention of cancer.

[0026] In certain embodiments, the cancer is selected from leukemia, lymphoma, myeloma, or solid tumor cancer (e.g., prostate cancer, lung cancer, breast cancer, pancreatic cancer, colon cancer, liver cancer, melanoma, and glioblastoma). In some embodiments, leukemia includes acute leukemia, chronic leukemia, myeloid leukemia, myeloid leukemia, lymphoblastic leukemia, lymphocytic leukemia, acute myelogeneous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), T-cell prolymphocytic leukemia (T-PLL), macrogranular lymphocytic leukemia, and hairy cell leukemia. This includes leukemia (HCL), MLL rearrangement leukemia, MLL-PTD leukemia, MLL amplification leukemia, MLL-positive leukemia, and leukemia exhibiting a HOX / MEIS1 gene expression signature.

[0027] In particular, the compounds and pharmaceutical compositions according to the present invention may be useful for the treatment or prevention of leukemia, especially nucleophosmin (NPM1) variant leukemia, such as NPM1c.

[0028] In some embodiments, the compound of formula (I) and its pharmaceutically acceptable salts and solvates may have improved metabolic stability properties.

[0029] In some embodiments, the compound of formula (I) and its pharmaceutically acceptable salts and solvates may have an extended in vivo half-life (T1 / 2).

[0030] In some embodiments, the compound of formula (I) and its pharmaceutically acceptable salts and solvates may have improved oral bioavailability.

[0031] In some embodiments, compounds of formula (I) and their pharmaceutically acceptable salts and solvates may reduce tumor growth, for example, tumors having rearrangements / modifications of the MLL(KMT2A) gene and / or NPM1 mutations.

[0032] In some embodiments, compounds of formula (I) and their pharmaceutically acceptable salts and solvates may have improved long-term in vivo PD properties, such as inhibition of target gene expression, including MEIS1, and upregulation of differentiation markers for at least 16 hours.

[0033] In some embodiments, compounds of formula (I) and their pharmaceutically acceptable salts and solvates may have an improved safety profile (e.g., reduced hERG inhibition, improved cardiovascular safety).

[0034] In some embodiments, the compound of formula (I) and its pharmaceutically acceptable salts and solvates may be suitable for QD administration (once daily).

[0035] The present invention also relates to the use of compounds of formula (I), pharmaceutically acceptable salts or solvates thereof, in combination with additional pharmaceuticals, for use in the treatment or prevention of cancers, including but not limited to leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN); and cancers, as well as cancers.

[0036] Furthermore, the present invention relates to a process for preparing a pharmaceutical composition according to the present invention, characterized in that a pharmaceutically acceptable carrier is homogeneously mixed with a therapeutically effective amount of a compound of formula (I), a pharmaceutically acceptable salt or solvate thereof.

[0037] The present invention also relates to products comprising compounds of formula (I), pharmaceutically acceptable salts or solvates thereof, and additional pharmaceuticals as combination preparations for simultaneous, separate, or sequential use in the treatment or prevention of diabetes, including but not limited to cancers such as leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN); and cancers, including but not limited to these.

[0038] Furthermore, the present invention relates to a method for treating or preventing a cell proliferation disorder in a warm-blooded animal, comprising administering to the animal an effective amount of a compound of formula (I) as defined herein, a pharmaceutically acceptable salt thereof, or a solvate thereof, or a pharmaceutical composition or combination as defined herein.

[0039] With respect to the compounds of formula (I) listed herein, any aspect and embodiment of the present invention described herein also applies to the compounds of formula (A). [Brief explanation of the drawing]

[0040] The summary of the invention and the modes for carrying out the invention described below will be better understood in conjunction with the accompanying drawings. For the purpose of illustrating the invention, the drawings show exemplary embodiments of the invention. However, the invention is not limited to the specific disclosures in the drawings. Of the drawings: [Figure 1]This is the powder X-ray diffraction (XRPD) pattern of compound 51 in its crystalline free base form. [Figure 2] This is the powder X-ray diffraction (XRPD) pattern of compound 51a in its crystalline HCl salt form. [Figure 3] This is an isotherm plot of the dynamic vapor sorption (DVS) of compound 51a in its crystalline HCl salt form. [Figure 4] This shows the dynamic vapor sorption (DVS) change in the mass plot of compound 51a in its crystalline HCl salt form. [Modes for carrying out the invention]

[0041] As used herein, the terms "halo" or "halogen" refer to fluoro, chloro, bromo, and iodine.

[0042] When used in this specification, the prefix "C x~y (where x and y are integers) refers to the number of carbon atoms in a given group. Therefore, C 1~6 Alkyl groups typically contain 1 to 6 carbon atoms.

[0043] When used in this specification, "C" is used as a base or part of a base. 1~4 The term "alkyl" refers to a linear or branched saturated hydrocarbon radical having 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, and t-butyl.

[0044] Similarly, when used herein, "C" as a base or part of a base 1~6 The term "alkyl" refers to a linear or branched saturated hydrocarbon radical having 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, t-butyl, n-pentyl, and n-hexyl.

[0045] Similarly, when used herein, "C" as a base or part of a base 1~8 The term "alkyl" refers to methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, t-butyl, n-pentyl, and n-hexyl.

[0046] [ka] This represents a linear or branched saturated hydrocarbon radical having 1 to 8 carbon atoms.

[0047] When used in this specification, "C" is used as a base or part of a base. 3~6 The term "cycloalkyl" defines saturated cyclic hydrocarbon radicals having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0048] When used in this specification, "C" is used as a base or part of a base. 3~7 The term "cycloalkyl" defines saturated cyclic hydrocarbon radicals having 3 to 7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.

[0049] It will be obvious to those skilled in the art that S(=O)2 or SO2 represents the sulfonyl moiety.

[0050] It will be obvious to those skilled in the art that CO or C (=O) represents the carbonyl portion.

[0051] Those skilled in the art will know that the basis for -NR etc.

[0052] [ka] It should be clear that this represents -NR. An example of such a base is -NR q - is

[0053] Non-limiting examples of "monocyclic 5- or 6-membered aromatic rings containing 1, 2, or 3 nitrogen atoms and optionally a carbonyl moiety" include, but are not limited to, pyrazolyl, imidazolyl, pyridinyl, pyridadinyl, pyrimidinyl, pyrazinyl, triazinyl, or 1,2-dihydro-2-oxo-4-pyridinyl.

[0054] Those skilled in the art will know that a monocyclic 5 or 6-membered aromatic ring containing 1, 2, or 3 nitrogen atoms and a carbonyl moiety is,

[0055] [ka] You will understand that this includes, but is not limited to, these.

[0056] The term "monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocyclyl" defines a complete or partially saturated cyclic hydrocarbon radical having 4 to 7 ring members bonded to the remainder of the molecule of formula (I) via a nitrogen atom, and containing at least one nitrogen atom and one or two additional heteroatoms each independently selected at will. Examples include N-bonded azetidinyl, N-bonded pyrrolidinyl, N-bonded morpholinyl, N-bonded thiomorpholinyl, N-bonded piperadinyl, N-bonded 1,4-diazepanyl, N-bonded piperidinyl, and N-bonded 1,2,3,6-tetrahydropyridinyl. Two R groups that, together, form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally, one additional heteroatom selected from O, S, and N, along with the N atom to which they are bonded.

[0057] The term "monocyclic carbon-bonded 4- to 7-membered complete or partially saturated heterocyclyl" defines a complete or partially saturated cyclic hydrocarbon radical having 4 to 7 ring members and containing 1, 2, or 3 heteroatoms each independently selected from O, S, and N, such as carbon-bonded azetidinyl, carbon-bonded pyrrolidinyl, carbon-bonded morpholinyl, carbon-bonded tetrahydrofuranyl, carbon-bonded thiolanyl, carbon-bonded oxetanyl, carbon-bonded thietanyl, carbon-bonded tetrahydropyranyl, carbon-bonded tetrahydrothiopyranyl, carbon-bonded piperidinyl, carbon-bonded azepanyl, carbon-bonded 1,3-dioxolanyl, and carbon-bonded 1,2,3,6-tetrahydropyridinyl.

[0058] To clarify, a 4- to 7-membered fully or partially saturated heterocyclyl has 4 to 7 ring members, including heteroatoms.

[0059] Non-limiting examples of "monocyclic carbon-bonded 5 or 6-membered aromatic rings each containing one, two, or three heteroatoms independently selected from O, S, and N" include, but are not limited to, carbon-bonded pyrazolyl, carbon-bonded imidazolyl, carbon-bonded pyridinyl, carbon-bonded triazolyl, carbon-bonded pyridazinyl, carbon-bonded pyrimidinyl, carbon-bonded oxazolyl, carbon-bonded furanyl, carbon-bonded isothiazolyl, carbon-bonded thiazolyl, carbon-bonded thiadiazolyl, carbon-bonded oxadiazolyl, or carbon-bonded pyrazinyl.

[0060] In the context of the present invention, bicyclic 6- to 11-membered complete or partially saturated heterocyclyl groups include condensed, spiro, and bridging bicyclic groups.

[0061] A fused bicyclic group is a set of two rings that share two atoms and the bond between them.

[0062] A spironicyclic group is a group of two rings bonded together at a single atom.

[0063] A bridging bicyclic group is a set of two rings that share three or more atoms.

[0064] Examples of bicyclic carbon-bonded 6- to 11-membered complete or partially saturated heterocyclines each containing one, two, or three heteroatoms independently selected from O, S, and N include:

[0065] [ka] These are some examples, but are not limited to these.

[0066] Examples of bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocyclines containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N, include:

[0067] [ka] These are some examples, but are not limited to these.

[0068] Two R groups that, together, form a 6- to 11-membered bicyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, along with the N atom to which they are bonded.

[0069] Examples of fused bicyclic carbon-bonded 9-10 member aromatic rings each containing 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N include:

[0070] [ka] These are some examples, but are not limited to these.

[0071] As used herein, the term "5-12 member saturated carbon bicyclic" system defines saturated condensed, spiro, and bridging bicyclic hydrocarbon systems having 5-12 carbon atoms. Examples of 5-12 member saturated carbon bicyclic systems include:

[0072] [ka] These are some examples, but are not limited to these.

[0073] A substituent, for example

[0074] [ka] When represented by chemical structures such as these, "----" indicates a bond to the remainder of the numerator in equation (I).

[0075] If any variable occurs more than once in any component, each definition is independent.

[0076] If any variable occurs more than once in any expression (for example, expression (I)), then each definition is independent.

[0077] Those skilled in the art will see that when a portion (e.g., a heterocyclyl or a monocyclic 5- or 6-membered aromatic ring) is substituted with two or more substituents (e.g., one, two, or three substituents) selected from a certain group, each substituent can be selected independently from that group, even if not explicitly mentioned.

[0078] In general, whenever the term “substituted” is used in the present invention, unless otherwise specified and evident from the context, it means that one or more hydrogen atoms in the atom or radical represented in the expression using “substituted,” specifically 1 to 4 hydrogen atoms, more specifically 1 to 3 hydrogen atoms, preferably 1 or 2 hydrogen atoms, more preferably 1 hydrogen atom, are replaced with an option from the specified group, provided that the normal valency is not exceeded, and that the substitution results in a chemically stable compound, i.e., a compound robust enough to withstand isolation to useful purity from the reaction mixture (post-reaction isolation, e.g., purification by silica gel chromatography). In certain embodiments, if the number of substituents is not explicitly specified, the number of substituents is 1.

[0079] A combination of substituents and / or variables is acceptable only if such a combination results in a chemically stable compound. In this context, "stable compound" means a compound that is robust enough to withstand isolation from the reaction mixture to a useful degree of purity (post-reaction isolation, e.g., purification by silica gel chromatography).

[0080] Those skilled in the art will understand that the term "optionally substituted" means that the atom or radical indicated in the expression using "optionally substituted" may or may not be substituted (meaning substituted or unsubstituted, respectively).

[0081] Where present on a moiety with two or more substituents, they may replace hydrogen atoms on the same atom, or they may replace hydrogen atoms on different atoms in that moiety, unless otherwise indicated or evident from the context.

[0082] In the context of this invention, "saturated" means "fully saturated" unless otherwise specified.

[0083] Unless otherwise specified and evident from the context, aromatic rings and heterocyclyl groups may be bonded to the remainder of the molecule of formula (I) through any available ring carbon atoms (C bonds) or nitrogen atoms (N bonds).

[0084] Unless otherwise specified and evident from the context, aromatic rings and heterocyclyl groups may optionally be substituted on carbon and / or nitrogen atoms, where possible, according to the embodiment. Those skilled in the art will understand that in such cases, the hydrogen atoms on the carbon and / or nitrogen atoms are replaced by such substituents.

[0085] Unless otherwise specified and it is clear from the context, the variable element R 21 and -YR 3 They can bond to any carbon or nitrogen atom of the ring to which they are bonded, however, R21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 The condition is that one of them is bonded to the nitrogen atom of the ring.

[0086] For example, R 21 -YR represents hydrogen. 3 If is bonded to the nitrogen atom of the ring in formula (I), then the compound of subformula (Ix) is obtained:

[0087] [ka]

[0088] If Y in formula (I) represents a covalent bond, then the compound of subformula (Iy) is obtained:

[0089] [ka]

[0090] In equation (I), Y is

[0091] [ka] When this is expressed, the compound of subformula (Iz) is obtained:

[0092] [ka]

[0093] As used herein, the term “subject” means an animal, preferably a mammal (e.g., a cat, a dog, a primate, or a human), more preferably a human, that is or has been the subject of treatment, observation, or experimentation.

[0094] When used herein, the term "therapeutic dose" means the amount of an active compound or medicinal product that elicits a biological or medical response in a tissue system, animal, or human, including relief or reversal of symptoms of the disease or disorder being treated, as sought by researchers, veterinarians, physicians, or other clinicians.

[0095] The term “composition” is intended to encompass products containing specific components in specific amounts, and any products obtained directly or indirectly from specific combinations of specific components in specific amounts.

[0096] As used herein, the term “treatment” is intended to refer to any process that can delay, interfere with, prevent, or halt the progression of a disease, but does not necessarily mean the complete disappearance of all symptoms.

[0097] As used herein, the terms “(the) compound of the present invention” or “compound according to the present invention” mean the compound of formula (I), as well as its pharmaceutically acceptable salts and solvates.

[0098] When used herein, any chemical formula having a bond that is shown only as a solid line and not as a solid wedge bond or a hashed wedge bond, or otherwise shown as having a specific arrangement (e.g., R, S) around one or more atoms, is intended to represent each possible stereoisomer, or a mixture of two or more stereoisomers.

[0099] In the above and below, the term "compound of formula (I)" means including its tautomers and stereoisomers.

[0100] The terms "stereoisomer," "stereoisomeric form," and "stereochemical isomer form" used above and below are interchangeable.

[0101] The present invention comprises all stereoisomers of the compounds of the present invention, either as pure stereoisomers or as mixtures of two or more stereoisomers.

[0102] Enantiomers are stereoisomers that are mirror images of each other and cannot be superimposed. A 1:1 mixture of a pair of enantiomers is a racemate or racemic mixture.

[0103] Atropisomers (or atropoiomers) are stereoisomers having a specific spatial configuration resulting from binding rotation around a single bond due to significant steric hindrance. All atropisomers of the compound of formula (I) are intended to be within the scope of this invention.

[0104] Diastereomers (or diastereoisomers) are stereoisomers that are not enantiomers; that is, they are not related as mirror images. If a compound contains a double bond, the substituent can be in an E or Z configuration.

[0105] Substituents on a divalent cyclic saturated or partially saturated radical may have either a cis configuration or a trans configuration. For example, if the compound contains a disubstituted cycloalkyl group, the substituent may be in either a cis or trans configuration.

[0106] Therefore, the present invention always includes enantiomers, atrop isomers, diastereomers, racemates, E isomers, Z isomers, cis isomers, trans isomers, and mixtures thereof, where chemically possible.

[0107] The meanings of all terms, namely enantiomer, atropisomer, diastereomer, racemate, E isomer, Z isomer, cis isomer, trans isomer, and mixtures thereof, are known to those skilled in the art.

[0108] The absolute configuration is determined according to the Cahn-Ingold-Prelog system. The configuration in asymmetric atoms is determined by either R or S. Decomposed stereoisomers whose absolute configuration is unknown are: They can be designated as (+) or (-) depending on the direction in which they rotate the plane polarization. For example, decomposed enantiomers whose absolute configuration is unknown can be designated as (+) or (-) depending on the direction in which they rotate the plane polarization.

[0109] When a specific stereoisomer is identified, this means that the stereoisomer is substantially free from other stereoisomers, i.e., it is associated with less than 50%, preferably less than 20%, more preferably less than 10%, even more preferably less than 5%, particularly less than 2%, and most preferably less than 1% of other stereoisomers. Therefore, when a compound of formula (I) is identified, for example, as (R), this means that the compound is substantially free from the (S) isomer; when a compound of formula (I) is identified, for example, as E, this means that the compound is substantially free from the Z isomer; and when a compound of formula (I) is identified, for example, as cis, this means that the compound is substantially free from the trans isomer.

[0110] Some of the compounds represented by formula (I) may also exist in tautomeric forms. Such forms, as far as they exist, are not explicitly shown in formula (I) above, but are intended to be included within the scope of this disclosure. Thus, a single compound may exist in both stereoisomeric and tautomeric forms.

[0111] Examples of pharmaceutically acceptable salts include acid addition salts and base addition salts. Such salts may be formed by conventional means, for example, by reacting a free acid form or a free base form with one or more equivalents of a suitable base or acid, optionally in a solvent or in a medium in which the salt is insoluble, and then removing the solvent or medium using standard techniques (e.g., by vacuum, by freeze-drying, or by filtration). Salts may also be prepared, for example, by exchanging a counterion of the compound of the present disclosure in salt form with another counterion using a suitable ion exchange resin.

[0112] The pharmaceutically acceptable salts referred to above or below include salt forms of therapeutically active, non-toxic acids and bases from which compounds of formula (I) and their solvates can be formed.

[0113] Suitable acids include, for example, hydrohalic acids, such as hydrochloric acid or hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and other inorganic acids; or, for example, organic acids such as acetic acid, propanoic acid, hydroxyacetic acid, lactic acid, pyruvic acid, oxalic acid (i.e., ethanedioic acid), malonic acid, succinic acid (i.e., butanedioic acid), maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclamic acid, salicylic acid, p-aminosalicylic acid, pamoic acid, and other organic acids. Conversely, the above salt forms can be converted to free salt forms by treatment with a suitable base.

[0114] Compounds of formula (I) containing acidic protons, or their solvates, may be converted to their non-toxic metal or amine salt forms by treatment with appropriate organic and inorganic bases.

[0115] Suitable base salt forms include, for example, ammonium salts, alkali and alkaline earth metal salts such as lithium, sodium, potassium, cesium, magnesium, and calcium salts; organic bases such as primary, secondary, and tertiary aliphatic amines and aromatic amines such as methylamine, ethylamine, propylamine, isopropylamine, the four butylamine isomers, dimethylamine, diethylamine, diethanolamine, dipropylamine, diisopropylamine, di-n-butylamine, pyrrolidine, piperidine, morpholine, trimethylamine, triethylamine, tripropylamine, quinuclidine, pyridine, quinoline, and isoquinoline salts; benzathine, N-methyl-glucamine, hydravamin salts, and amino acid salts such as arginine and lysine. Conversely, base forms can be converted to free base forms by treatment with acid.

[0116] The term "prodrug" includes any compound that, whether administered orally or parenterally, and especially after oral administration, is metabolized in vivo in experimentally detectable amounts and within a specified time frame (e.g., within a 0.5–24 hour dosing interval, or, for example, within a 6–24 hour dosing interval (i.e., 1–4 times per day)) to a more active form. To avoid misunderstanding, the term "parenteral" administration includes all forms of administration other than oral administration, specifically intravenous (IV), intramuscular (IM), and subcutaneous (SC) injections.

[0117] Prodrugs can be prepared by modifying functional groups present on a compound such that the modifications are cleaved in vivo when the prodrug is administered to a mammalian subject. The modifications are typically achieved by synthesizing a parent compound having the prodrug substituent. Generally, prodrugs include compounds in which a hydroxyl group, amino group, sulfhydryl group, carboxyl group, or carbonyl group is bonded to any group that can be cleaved in vivo to regenerate a free hydroxyl group, amino group, sulfhydryl group, carboxyl group, or carbonyl group, respectively.

[0118] Examples of prodrugs include, but are not limited to, esters and carbamates of hydroxyl functional groups, ester groups of carboxyl functional groups, N-acyl derivatives, and N-Mannich bases. General information on prodrugs can be found, for example, in Bundegaard, H. "Design of Prodrugs" pl-92, Elesevier, New York-Oxford (1985).

[0119] The term solvate includes the solubilated forms that the compound of formula (I) can form, as well as its salts. Examples of such solubilated forms include hydrates, alkoxides, and so on.

[0120] The compounds of the present invention, prepared by the processes described below, may be synthesized in the form of enantiomer mixtures, particularly racemic mixtures of enantiomers, which can be separated from each other by decomposition procedures known in the art. Methods for separating the enantiomer forms of the compound of formula (I), as well as its pharmaceutically acceptable salts and solvates, include liquid chromatography using a chiral stationary phase. The pure stereochemical isomers may also be derived from the corresponding pure stereochemical isomers of suitable starting materials, provided that the reaction occurs stereospecifically. Preferably, if a particular stereoisomer is desired, the compound will be synthesized by a stereospecific preparation method. These methods will advantageously employ enantiomerically pure starting materials.

[0121] As used herein, the term “enantiomerically pure” means that the product contains at least 80% by weight of one enantiomer and 20% by weight or less of another enantiomer. Preferably, the product contains at least 90% by weight of one enantiomer and 10% by weight or less of another enantiomer. In the most preferred embodiment, the term “enantiomerically pure” means that the composition contains at least 99% by weight of one enantiomer and 1% by weight or less of another enantiomer.

[0122] The present invention also includes isotope-labeled compounds of the present invention that are identical to those enumerated herein, due to the fact that one or more atoms are replaced by atoms (or the most abundant atoms found in nature) having atomic masses or mass numbers different from those normally found in nature.

[0123] All isotopes and isotopic mixtures of any particular atom or element identified herein, whether naturally occurring in their natural abundance or in isotopic-enriched forms, or produced synthetically, are intended within the scope of the compounds of the present invention. Exemplary isotopes that can be incorporated into the compounds of the present invention include those of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine.2 H, 3 H, 11 C, 13 C, 14 C, 13 N, 15 O, 17 O, 18 O, 32 P, 33 P, 35 S, 18 F, 36 Cl, 122 I, 123 I, 125 I, 131 I, 75 Br, 76 Br, 77 Br, and 82 Examples include Br. Preferably, the isotope is 2 H, 3 H, 11 C, 13 C, and 18 Selected from group F. Preferably, the isotope is 2 H, 3 H, 11 C, and 18 Selected from group F. More preferably, the isotope is 2 H, 3 H, or 13 It is C. More preferably, the isotope is 2 H or 13 It is C. More preferably, the isotope is 2 It is H. In particular, deuterium compounds and 13 C-enriched compounds are intended to be included within the scope of the present invention. In particular, deuterium compounds are intended to be included within the scope of the present invention.

[0124] A specific isotope-labeled compound of the present invention (for example, 3 H and 14 Those labeled with 1C may be useful, for example, in substrate tissue distribution assays. Tritiated ( 3 H) and carbon-14( 14 C) Isotopes are useful for their ease of preparation and detection. Furthermore, heavier isotopes, such as deuterium (i.e., 2Substitution with H), etc., can lead to increased metabolic stability (e.g., increased half-life in vivo or reduced required dose), resulting in certain therapeutic benefits and therefore being preferable depending on the circumstances. For example, 15 O, 13 N, 11 C, and 18 Positron-emitting isotopes such as fluorine (F) are useful in positron emission tomography (PET) studies. PET imaging in cancer has proven useful in locating and identifying tumors, determining disease stage, and deciding on appropriate treatment. Human cancer cells overexpress many receptors or proteins that are potential disease-specific molecular targets. Radiolabeled tracers that bind with high affinity and specificity to such receptors or proteins on tumor cells have great potential for diagnostic imaging and targeted radionuclide therapy (Charron, Carlie L. et al. Tetrahedron Lett. 2016, 57(37), 4119-4127). Furthermore, target-specific PET radiotactic tracers can be used as biomarkers to investigate and evaluate pathology, for example, by measuring target expression and therapeutic response (Austin R. et al. Cancer Letters (2016), doi:10.1016 / j.canlet.2016.05.008).

[0125] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y - or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, halo, -C(=O)-NR xa R xb -S(=O)2-R 18 -C(=O)-OC 1~4 Alkyl, or

[0126] [ka] This represents, R 18 However, C 1~6 Represents alkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, or R 18 and R 19 These combine to form -(CH2)3-, -(CH2)4-, or -(CH2)5-, R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6 Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl and -C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl-OH, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline is C 1~4 alkyl, -OH, -OC 1~4 Alkyl and 1, 2, or 3 OR 23 C replaced by 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xbThese combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected independently from O, S, and N (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may be optionally substituted with one, two, or three -OH substituents), R 23 However, hydrogen or C 1~4 Represents alkyl, R 1b However, F or -OC 1~4 Represents alkyl, R 2 But, hello, C 1~4 C substituted with alkyl or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3a This represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each is independent, covalently bonded or

[0127] [ka] This represents, R 5 However, it represents hydrogen, n1 is selected from 1 and 2. n2 is selected from 1, 2, and 3. R y However, it represents hydrogen, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;C 1~8 Alkyl; and each independently -C(=O)-Het6a -C(=O)-Het 6b , -NR 10c -C(=O)-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, Halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 Ar 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8 Represents alkyl, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl;-(C=O)-C 1~4 Alkyl; and 1, 2, or 3 -OCs 1~4C substituted with alkyl 1~6 selected from the group consisting of alkyl Ar 1 is optionally, each independently, C 1~4 alkyl and -C(=O)-NR 10a R 10b represents phenyl substituted with 1, 2, or 3 substituents selected from the group consisting of Het 1 each independently contains 1, 2, or 3 heteroatoms selected from O, S, and N, a monocyclic C-bonded 4- to 7-membered fully or partially saturated heterocyclyl (wherein the S atom may be substituted to form S(=O) or S(=O)2), or each independently contains 1, 2, or 3 heteroatoms selected from O, S, and N, a bicyclic C-bonded 6- to 11-membered fully or partially saturated heterocyclyl (wherein the S atom may be substituted to form S(=O) or S(=O)2 i) represents , the heterocyclyl is optionally substituted on one nitrogen with R 6 , -C(=O)-Cy 1 , and -C(=O)-R 8 ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​6a , Het 6b C substituted with one or two substituents selected from the group consisting of , and -OH 1~6 Selected from the group consisting of alkyl groups, R 8 However, hydrogen, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, cyano, -S(=O)2-C 1~4 Alkyl, and Het 3a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 and Het 3a However, each contains independently one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -(C=O)-C on one nitrogen atom). 1~4 (represented by alkyl substitution) Het 4 However, each contains one, two, or three heteroatoms independently selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring (in which case, the aromatic ring may optionally have one or two carbon atoms, each independently of N). 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have halo and -S(=O)2-C atoms on one or two carbon atoms, each independently). 1~4The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl and -S(=O)2-C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 6b However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 1 However, C can be optionally substituted with 1, 2, or 3 -OH groups. 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, and C 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) R 9a and R 9b However, each independently, hydrogen, C 1~4 Alkyl, -C(=O)-C 1~4 (represented by alkyl substitution), -S(=O)2-C 1~4 Alkyl and -C(=O)-R 14 Selected from the group consisting of, R 10a , R 10b , and R 10c However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R10d and R 10e each independently represents C 1~4 alkyl or -O-C 1~4 alkyl, and is selected from the group consisting of R 14 represents -O-C 1~4 alkyl] relates to compounds thereof, as well as their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0128] The present invention particularly relates to formula (I) as defined herein, wherein Q represents -CHR y -, R 1a represents -C(=O)-NR xa R xb -, -S(=O)2-R 18 -, -C(=O)-O-C 1~4 alkyl, or

[0129]

Chemical formula

[0130] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb -S(=O)2-R 18 -C(=O)-OC 1~4 Alkyl, or

[0131] [ka] This represents, R 18 However, C 1~6 Represents alkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, or or R 18 and R 19 They come together to form -(CH2)3-, R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6 Cycloalkyl, and C 1~6Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl and -C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl-OH, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline is C 1~4 alkyl, -OH, -OC 1~4 Alkyl, and 1, 2, or 3 OR 23 C replaced by 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected independently from O, S, and N (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may be optionally substituted with one, two, or three -OH substituents), R 23 However, hydrogen or C 1~4 Represents alkyl, R 1b However, F or -OC 1~4 Represents alkyl, R 2 But, hello, C 1~4 C substituted with alkyl or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3aThis represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each independently represents a covalent bond. n1 is selected from 1 and 2. n2 is selected from 1, 2, and 3. R y However, it represents hydrogen, R 3 and R 3a However, each is independent, Het 1 ;C 1~8 Alkyl; and each independently -C(=O)-Het 6a -C(=O)-Het 6b , -NR 10c -C(=O)-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, Halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 Ar 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8 Selected from the group consisting of alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xcand R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing, together with the N atom to which they bond, one N atom and one or two additional heteroatoms, each independently selected independently from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain one, two, or three -(C=O)-C 1~4 (Substituted with alkyl) R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl;-(C=O)-C 1~4 Alkyl; and 1, 2, or 3 -OCs 1~4 C substituted with alkyl 1~6 Selected from the group consisting of alkyl groups, Ar 1 However, you can choose one, two, or three -C(=O)-NRs. 10a R 10b This represents phenyl substituted with, Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms, each independently of a halo, C 1~4 Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl, oxo, and -OH. , Het 2However, it represents C-linked pyrazolyl, 1,2,4-oxadiazolyl, or pyridazinyl. R 6 However, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-C(=O)-Het 6a ;-C(=O)-NR 10d R 10e ;-C(=O)-OC 1~4 Alkyl;-S(=O)2-C 1~4 Alkyl; optional, each independently Het 6a , Het 6b C substituted with one or two substituents selected from the group consisting of , and -OH 1~6 Selected from the group consisting of alkyl groups, R 8 However, hydrogen, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, cyano, and Het 3a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 and Het 3a However, each contains independently 1, 2, or 3 heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -(C=O)-C on one nitrogen atom). 1~4 (represented by alkyl substitution) Het 4 However, each contains one, two, or three heteroatoms independently selected from O, S, and N in a monocyclic carbon-bonded 5 or 6-membered aromatic ring (in which case, the aromatic ring optionally contains a total of one or two -(C=O)-NR atoms on one or two carbon atoms). 10a R 10b (represented by being replaced by) Het 6aHowever, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be substituted on one or two carbon atoms with a total of 1, 2, 3, or 4 halos, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 Alkyl and -S(=O)2-C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 6b However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 1 However, C can be optionally substituted with 1, 2, or 3 -OH groups. 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, and C 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) R 9a and R 9b However, each independently, hydrogen, C 1~4 Alkyl, -C(=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -C(=O)-R 14Selected from the group consisting of, R 10a , R 10b , and R 10c However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 10d and R 10e However, each is independent, C 1~4 Alkyl and -OC 1~4 Selected from the group consisting of alkyl groups, R 14 However, -OC 1~4 [Represents alkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0132] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y - or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, halo, -C(=O)-NR xa R xb -S(=O)2-R 18 -C(=O)-OC 1~4 Alkyl,

[0133] [ka] This represents, R 18 However, C 1~6 Represents alkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, or R 18 and R 19 They come together to form -(CH2)3-, R xa and R xb Each of them independently consists of hydrogen and Het 3 , C 3~6Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl and -C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl-OH, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline is C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl and OR 23 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected independently from O, S, and N (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may be optionally substituted with one, two, or three -OH substituents), R 23 However, hydrogen or C 1~4 Represents alkyl, R 1b However, it represents F, R 2 But, hello, C 1~4 C substituted with alkyl or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R3a This represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each is independent, covalently bonded or

[0134] [ka] This represents, n1 is selected from 1 and 2. n2 is selected from 1, 2, and 3. R y However, it represents hydrogen, R 5 However, it represents hydrogen, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C 1~8 Alkyl; and each independently -C(=O)-Het 6a -C(=O)-Het 6b , -NR 10c -C(=O)-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, Halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 Ar 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8 Selected from the group consisting of alkyl groups, R xc and R xdThese combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), R 8a and R 8b However, each independently, hydrogen;C 1~6 alkyl; and one -OC 1~4 C substituted with alkyl 1~6 Selected from the group consisting of alkyl groups, Ar 1 However, each can be chosen independently of C 1~4 Alkyl and -C(=O)-NR 10a R 10b Represents phenyl substituted with one, two, or three substituents selected from the group consisting of the following: Het 1However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , C 1~4 Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl, oxo, and -OH. , Het 2 However, this represents C-linked pyrazolyl, 1,2,4-oxadiazolyl, pyridazinyl, or triazolyl. R 6 However, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-C(=O)-Het 6a ;-C(=O)-NR 10d R 10e ;-C(=O)-OC 1~4 Alkyl;-S(=O)2-C 1~4 Alkyl; optionally, C substituted with one or two -OH substituents. 1~6 Alkyl; and C 3~6 Selected from the group consisting of cycloalkyl groups, R 8 However, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, cyano, -S(=O)2-C 1~4 Alkyl, and Het 3aC substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 and Het 3a However, each contains independently 1, 2, or 3 heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be substituted with an oxo atom on one carbon atom, and the heterocycline may optionally be -(C=O)-C on one nitrogen atom). 1~4 (represented by alkyl substitution) Het 4 However, each contains one, two, or three heteroatoms independently selected from O, S, and N in a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, three, or four heteroatoms independently selected from O, S, and N in a fused bicyclic 9- or 10-membered aromatic ring with carbon bonds (in which case, the aromatic ring may optionally contain one or two carbon atoms, each independently of C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have halo and -S(=O)2-C atoms on one or two carbon atoms, each independently). 1~4 The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl and -S(=O)2-C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 6bHowever, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 1 However, C can be optionally substituted with 1, 2, or 3 -OH groups. 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 A cycloalkyl group or the carbon bicyclic system is optionally selected, and each is independently R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, and C 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) R 9a and R 9b However, each independently, hydrogen, C 1~4 Alkyl, -C(=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -C(=O)-R 14 Selected from the group consisting of, R 10a , R 10b , and R 10c However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 10d and R 10e However, each is independent, C 1~4 Alkyl and -OC 1~4 Selected from the group consisting of alkyl groups, R 14 However, -OC 1~4 [Represents alkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0135] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y -, -O-, -C(=O)-, -NR q -, or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, cyano, halo, het, -C(=O)-NR xa R xb -S(=O)2-R 18 ,

[0136] [ka] This represents, R 18 However, C 1~6 Alkyl or C 3~6 Represents cycloalkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, Het is a monocyclic 5 or 6-membered aromatic ring containing 1, 2, or 3 nitrogen atoms and optionally a carbonyl moiety (in this case, the monocyclic 5 or 6-membered aromatic ring optionally contains C 1~4 Alkyl, C 3~6 (represented by being substituted with one, two, or three substituents selected from the group consisting of cycloalkyl or cyano) R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6 Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl and NR 11c R 11d(Substituted with 1, 2, or 3 substituents selected from the group consisting of, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 1b However, it represents hydrogen, F, or Cl. R 2 But, hello, C 3~6 Cycloalkyl, C 1~4 Alkyl, -OC 1~4 C substituted with alkyl, cyano, or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3a This represents, however, R 21 ga-Y a -R3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each is independent, covalently bonded or

[0137] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, hydrogen, -OH, C 1~4 Alkyl, -C 1~4 Alkyl-OH, or -C 1~4 Alkyl-OC 1~4 Represents alkyl, R q However, hydrogen or C 1~4 Represents alkyl, R 5 However, hydrogen, C 1~4 Alkyl, or C 3~6 Represents cycloalkyl, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C 1~6 Alkyl; and each independently -C(=O)-NR 10a R 10b , -NR 10c -C(=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, cyano, halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R xc However, Cy 1 , Het 5 , -C 1~6 Alkyl-Cy 1 , -C 1~6 Alkyl-Het 3 , -C 1~6 Alkyl-Het 4 , or -C 1~6 Represents alkylphenyl, R xd However, hydrogen; C 1~4 alkyl; or halo, -OH, -OC 1~4 C substituted with one, two, or three substituents selected from the group consisting of alkyl and cyano 1~4 Represents alkyl, or R xc and R xd These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl-S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4 Alkyl, -C(=O)-NR 10a R 10b , and -NR 10c -C(=O)-C 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 1~6 Selected from the group consisting of alkyl groups, Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH. , Het 2 However, this represents a C-bonded pyrazolyl or triazolyl, which can be optionally placed on one nitrogen atom, R 6a It may be replaced with, R 6 and R 6a However, each is independent, Het 3 ;Het4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-S(=O)2-C 1~4 Alkyl; optional, each independently Het 3 , Het 4 , Het 6a , Het 6b Cy 1 -CN, -OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl-C 3~6 Cycloalkyl, -C(=O)-OH, -NR 11a R 11b , and -NH-S(=O)2-C 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 1~6 Alkyl; and optionally, -CN, -OH, -OC, each independently. 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, and optionally OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl and -NH-S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 3~6 Selected from the group consisting of cycloalkyl groups, R 8 However, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, Halo, Cyano, -NR 11a R 11b , Het 3a , and Het 6a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 , Het 3a , Het 5, and Het 5a However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline may optionally have a carbon atom on one carbon atom, C 1~4 Alkyl, halo, -OH, -NR 11a R 11b , or substituted with an oxo, and the heterocyclyl optionally has a C on one nitrogen atom. 1~4 Substituted with alkyl , Het 4 and Het 7 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring, or each may independently contain one, two, three, or four heteroatoms selected from O, S, and N in a fused bicyclic carbon bond 9 or 10-membered aromatic ring (in which case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 Alkyl or -(C=O)-OC 1~4 The aromatic ring is substituted, and optionally, on one or two carbon atoms, each independently, -OH, halo, C 1~4 Alkyl, -OC 1~4 Alkyl, -NR 11a R 11b , C 1~4 Alkyl-NR 11a R 11b -NH-C(=O)-C 1~4 Alkyl, cyano, -COOH, -NH-C(=O)-OC 1~4 Alkyl, -NH-C(=O)-Cy 3 -NH-C(=O)-NR 10a R 10b -(C=O)-OC 1~4Alkyl, -NH-S(=O)2-C 1~4 Alkyl, Het 8a , -C 1~4 Alkyl-Het 8a , Het 8b , Het 9 , and -C(=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a , Het 8 , and Het 8a However, each contains independently one N atom and optionally, each independently selected from O, S, and N, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have, on one or two carbon atoms, each independently, a halo, -OH, oxo, or -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 -(C=O)-NR 10a R 10b ,-OC 3~6 Cycloalkyl, -S(=O)2-C 1~4 Alkyl, cyano, C 1~4 Alkyl, -C 1~4 alkyl-OH, -OC 1~4 Alkyl, -O-(C=O)-NR 10a R 10b , and -O-(C=O)-C 1~4 The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by a substituent selected from the group consisting of) Het 6b and Het 8bHowever, each contains independently one N atom and optionally, independently, one or two additional heteroatoms selected from O, S, and N, forming a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have one or two carbon atoms independently of each other C 1~4 Alkyl, -OH, oxo, -(C=O)-NR 10a R 10b -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 , and -OC 1~4 The heterocyclyl is substituted with a total of one or two substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -C(=O)-Cy 3 -(C=O)-C 1~4 alkyl-OH, -C(=O)-C 1~4 Alkyl-OC 1~4 Alkyl, -C(=O)-C 1~4 Alkyl-NR 11a R 11b , and C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 9 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 The alkyl group is substituted, and the aromatic ring may optionally have -OH, halo, and C on one or two carbon atoms, each independently. 1~4 (Represents a group consisting of alkyl groups, which consists of a total of one or two substituents selected from the group,) Cy 1 However, at the discretion of choice, -OH, -NH-C(=O)-C 1~4 Alkyl, C 1~4 Alkyl, -NH-S(=O)2-C 1~4Alkyl, -S(=O)2-C 1~4 Alkyl and -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, C 1~4 Alkyl,

[0138] [ka] Furthermore, each independently of Het 3a , Het 6a , Het 6b , and -NR 9a R 9b C substituted with one or two substituents selected from the group consisting of 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) Cy 3 However, C 3~7 Cycloalkyl (in this case, the C 3~7 This represents a cycloalkyl group that is optionally substituted with one, two, or three halo substituents. R 9a and R 9b However, each independently, hydrogen;C 1~4 Alkyl; C 3~6 Cycloalkyl;-C(=O)-C 1~4 Alkyl;-C(=O)-C 3~6 Cycloalkyl;-S(=O)2-C 1~4 Alkyl; Het 5 ;Het 7 ;-C 1~4 Alkyl-R 16 ;-C(=O)-C1~4 Alkyl-Het 3a ;-C(=O)-R 14 ; Hal, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 3~6 Cycloalkyl; as well as halo, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 1~4 Selected from the group consisting of alkyl groups, R 11a , R 11b , R 13a , R 13b , R 15a , R 15b , R 17a , R 17b , R 20a , and R 20b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 11c and R 11d However, each independently, hydrogen, C 1~6 Alkyl and -C(=O)-C 1~4 Selected from the group consisting of alkyl groups, R 10a and R 10b However, each independently, hydrogen, C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 14 However, Het 5a ;Het 7 ;Het 8a ;-OC 1~4 Alkyl;-C(=O)NR 15a R 15b ;-OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halo 3~6 Cycloalkyl; or -OC 1~4 Alkyl, -NR 13a R 13b, halo, cyano, -OH, het 8a , and Cy 1 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 Represents alkyl, R 16 However, -C(=O)-NR 17a R 17b -S(=O)2-C 1~4 Alkyl, Het 5 , Het 7 , or Het 8 [represents] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0139] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y -, -O-, -C(=O)-, -NR q -, or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, cyano, halo, het, -C(=O)-NR xa R xb -S(=O)2-R 18 ,

[0140] [ka] This represents, R 18 However, C 1~6 Alkyl or C 3~6 Represents cycloalkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, Het is a monocyclic 5 or 6-membered aromatic ring containing 1, 2, or 3 nitrogen atoms and optionally a carbonyl moiety (in this case, the monocyclic 5 or 6-membered aromatic ring optionally contains C 1~4 Alkyl, C 3~6(represented by being substituted with one, two, or three substituents selected from the group consisting of cycloalkyl or cyano) R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6 Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl and NR 11c R 11d (Substituted with 1, 2, or 3 substituents selected from the group consisting of, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 1b However, it represents hydrogen, F, or Cl. R 2 But, hello, C 3~6 Cycloalkyl, C 1~4 Alkyl, -OC 1~4 C substituted with alkyl, cyano, or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3a This represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each is independent, covalently bonded or

[0141] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, hydrogen, -OH, C 1~4 Alkyl, -C 1~4 Alkyl-OH, or -C 1~4 Alkyl-OC 1~4 Represents alkyl, R q However, hydrogen or C 1~4 Represents alkyl, R 5 However, hydrogen, C 1~4 Alkyl, or C 3~6 Represents cycloalkyl, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C 1~6 Alkyl; and each independently -C(=O)-NR 10a R10b -S(=O)2-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, cyano, halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R xc However, Cy 1 , Het 5 , -C 1~6 Alkyl-Cy 1 , -C 1~6 Alkyl-Het 3 , -C 1~6 Alkyl-Het 4 , or -C 1~6 Represents alkylphenyl, R xd However, hydrogen; C 1~4 alkyl; or halo, -OH, -OC 1~4 C substituted with one, two, or three substituents selected from the group consisting of alkyl and cyano 1~4 Represents alkyl, or R xc and R xd These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xc and R xdThese combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl-S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4 Alkyl and -C(=O)NR 10a R 10b C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4Alkyl, oxo, -NR 9a R 9b Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH. , Het 2 However, this represents a C-bonded pyrazolyl or triazolyl, which can be optionally placed on one nitrogen atom, R 6a It may be replaced with, R 6 and R 6a However, each is independent, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-S(=O)2-C 1~4 Alkyl; optional, each independently Het 3 , Het 4 , Het 6a , Het 6b Cy 1 -CN, -OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl-C 3~6 Cycloalkyl, -C(=O)-OH, -NR 11a R 11b , and -NH-S(=O)2-C 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 1~6 Alkyl; and optionally, -CN, -OH, -OC, each independently. 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, and optionally OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl and -NH-S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 3~6 Selected from the group consisting of cycloalkyl groups, R 8However, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, Halo, Cyano, -NR 11a R 11b , Het 3a , and Het 6a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 , Het 3a , Het 5 , and Het 5a However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). Represents The heterocycline may optionally have a carbon atom on one carbon atom, C 1~4 Alkyl, halo, -OH, -NR 11a R 11b , or substituted with an oxo, and the heterocyclyl optionally has a C on one nitrogen atom. 1~4 Substituted with alkyl , Het 4 and Het 7 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring, or each may independently contain one, two, three, or four heteroatoms selected from O, S, and N in a fused bicyclic carbon bond 9 or 10-membered aromatic ring (in which case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 Alkyl or -(C=O)-OC 1~4 The aromatic ring is substituted, and optionally, on one or two carbon atoms, each independently, -OH, halo, C 1~4 Alkyl, -OC1~4 Alkyl, -NR 11a R 11b , C 1~4 Alkyl-NR 11a R 11b -NH-C(=O)-C 1~4 Alkyl, cyano, -COOH, -NH-C(=O)-OC 1~4 Alkyl, -NH-C(=O)-Cy 3 -NH-C(=O)-NR 10a R 10b -(C=O)-OC 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, Het 8a , -C 1~4 Alkyl-Het 8a , Het 8b , Het 9 , and -C(=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a , Het 8 , and Het 8a However, each contains independently one N atom and optionally, each independently selected from O, S, and N, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have, on one or two carbon atoms, each independently, a halo, -OH, oxo, or -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 -(C=O)-NR 10a R 10b ,-OC 3~6 Cycloalkyl, -S(=O)2-C 1~4 Alkyl, cyano, C 1~4 Alkyl, -C 1~4 alkyl-OH, -OC 1~4 Alkyl, -O-(C=O)-NR 10a R 10b , and -O-(C=O)-C 1~4The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by a substituent selected from the group consisting of) Het 6b and Het 8b However, each contains independently one N atom and optionally, independently, one or two additional heteroatoms selected from O, S, and N, forming a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have one or two carbon atoms independently of each other C 1~4 Alkyl, -OH, oxo, -(C=O)-NR 10a R 10b -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 , and -OC 1~4 The heterocyclyl is substituted with a total of one or two substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -C(=O)-Cy 3 -(C=O)-C 1~4 alkyl-OH, -C(=O)-C 1~4 Alkyl-OC 1~4 Alkyl, -C(=O)-C 1~4 Alkyl-NR 11a R 11b , and C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 9 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally have a carbon atom on one nitrogen atom).1~4 The alkyl group is substituted, and the aromatic ring may optionally have -OH, halo, and C on one or two carbon atoms, each independently. 1~4 (Represents a group consisting of alkyl groups, which consists of a total of one or two substituents selected from the group,) Cy 1 However, at the discretion of choice, -OH, -NH-C(=O)-C 1~4 Alkyl, C 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, C 1~4 Alkyl,

[0142] [ka] Furthermore, each independently of Het 3a , Het 6a , Het 6b , and -NR 9a R 9b C substituted with one or two substituents selected from the group consisting of 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) Cy 3 However, C 3~7 Cycloalkyl (in this case, the C 3~7 This represents a cycloalkyl group that is optionally substituted with one, two, or three halo substituents. R 9a and R9b However, each independently, hydrogen;C 1~4 Alkyl; C 3~6 Cycloalkyl;-C(=O)-C 1~4 Alkyl;-C(=O)-C 3~6 Cycloalkyl;-S(=O)2-C 1~4 Alkyl; Het 5 ;Het 7 ;-C 1~4 Alkyl-R 16 ;-C(=O)-C 1~4 Alkyl-Het 3a ;-C(=O)-R 14 ; Hal, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 3~6 Cycloalkyl; as well as halo, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 1~4 Selected from the group consisting of alkyl groups, R 11a , R 11b , R 13a , R 13b , R 15a , R 15b , R 17a , R 17b , R 20a , and R 20b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 11c and R 11d However, each independently, hydrogen, C 1~6 Alkyl and -C(=O)-C 1~4 Selected from the group consisting of alkyl groups, R 10a and R 10b However, each independently, hydrogen, C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 14 However, Het 5a;Het 7 ;Het 8a ;-OC 1~4 Alkyl;-C(=O)NR 15a R 15b ;-OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halo 3~6 Cycloalkyl; or -OC 1~4 Alkyl, -NR 13a R 13b , halo, cyano, -OH, het 8a , and Cy 1 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 Represents alkyl, R 16 However, -C(=O)-NR 17a R 17b -S(=O)2-C 1~4 Alkyl, Het 5 , Het 7 , or Het 8 [represents] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0143] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y -, -O-, -C(=O)-, -NR q -, or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, cyano, halo, het, -C(=O)-NR xa R xb -S(=O)2-R 18 ,

[0144] [ka] This represents, R 18 However, C 1~6 Alkyl or C3~6 Represents cycloalkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, Het is a monocyclic 5 or 6-membered aromatic ring containing 1, 2, or 3 nitrogen atoms and optionally a carbonyl moiety (in this case, the monocyclic 5 or 6-membered aromatic ring optionally contains C 1~4 Alkyl, C 3~6 (represented by being substituted with one, two, or three substituents selected from the group consisting of cycloalkyl or cyano) R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6 Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl and NR 11c R 11d (Substituted with 1, 2, or 3 substituents selected from the group consisting of, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xa and R xbThese combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 1b However, it represents hydrogen, F, or Cl. R 2 But, hello, C 3~6 Cycloalkyl, C 1~4 Alkyl, -OC 1~4 C substituted with alkyl, cyano, or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3a This represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y a However, each is independent, covalently bonded or

[0145] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, hydrogen, -OH, C 1~4 Alkyl, -C 1~4 Alkyl-OH, or -C 1~4 Alkyl-OC 1~4 Represents alkyl, Rq However, hydrogen or C 1~4 Represents alkyl, R 5 However, hydrogen, C 1~4 Alkyl, or C 3~6 Represents cycloalkyl, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C 1~6 Alkyl; and each independently -C(=O)-NR 10a R 10b , -NR 10c -C(=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, cyano, halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R xc However, Cy 1 , Het 5 , -C 1~6 Alkyl-Cy 1 , -C 1~6 Alkyl-Het 3 , -C 1~6 Alkyl-Het 4 , or -C 1~6 Represents alkylphenyl, R xd is hydrogen; C 1~4 alkyl; or halo, -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano 1~4 Represents alkyl, or R xc and R xdThese combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl-S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4 Alkyl, -C(=O)-NR 10a R 10b , and -NR 10c -C(=O)-C 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 1~6 Selected from the group consisting of alkyl groups, Het 1However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C bond 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have R on one nitrogen atom). 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b This represents a compound (which is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of -OH), Het 2 However, this represents a C-bonded pyrazolyl or triazolyl, which can be optionally placed on one nitrogen atom, R 6a It may be replaced with, R 6 and R 6a However, each is independent, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-S(=O)2-C 1~4 Alkyl; optional, each independently Het 3 , Het 4 , Het 6a , Het 6b Cy 1 -CN, -OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl-C 3~6 Cycloalkyl, -C(=O)-OH, -NR 11a R 11b , and -NH-S(=O)2-C 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 1~6Alkyl; and optionally, -CN, -OH, -OC, each independently. 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, and optionally OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl and -NH-S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 3~6 Selected from the group consisting of cycloalkyl groups, R 8 However, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, Halo, Cyano, -NR 11a R 11b , Het 3a , and Het 6a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 , Het 3a , Het 5 , and Het 5a However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline may, at its discretion, have a carbon atom on one carbon atom, C 1~4 Alkyl, halo, -OH, -NR 11a R 11b , or substituted with an oxo, and the heterocyclyl optionally has a C on one nitrogen atom. 1~4 Substituted with alkyl , Het 4 and Het 7 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring, or each may independently contain one, two, three, or four heteroatoms selected from O, S, and N in a fused bicyclic carbon bond 9 or 10-membered aromatic ring (in which case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 Alkyl or -(C=O)-OC 1~4 The aromatic ring is substituted, and optionally, on one or two carbon atoms, each independently, -OH, halo, C 1~4 Alkyl, -OC 1~4 Alkyl, -NR 11a R 11b , C 1~4 Alkyl-NR 11a R 11b -NH-C(=O)-C 1~4 Alkyl, cyano, -COOH, -NH-C(=O)-OC 1~4 Alkyl, -NH-C(=O)-Cy 3 -NH-C(=O)-NR 10a R 10b -(C=O)-OC 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, Het 8a , -C 1~4 Alkyl-Het 8a , Het 8b , Het 9 , and -C(=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a , Het 8 , and Het 8aHowever, each contains independently one N atom and optionally, each independently selected from O, S, and N, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have, on one or two carbon atoms, each independently, a halo, -OH, oxo, or -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 -(C=O)-NR 10a R 10b ,-OC 3~6 Cycloalkyl, -S(=O)2-C 1~4 Alkyl, cyano, C 1~4 Alkyl, -C 1~4 alkyl-OH, -OC 1~4 Alkyl, -O-(C=O)-NR 10a R 10b , and -O-(C=O)-C 1~4 The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by a substituent selected from the group consisting of) Het 6b and Het 8b However, each contains independently one N atom and optionally, independently, one or two additional heteroatoms selected from O, S, and N, forming a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have one or two carbon atoms independently of each other C 1~4 Alkyl, -OH, oxo, -(C=O)-NR 10a R 10b -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 , and -OC 1~4The heterocyclyl is substituted with a total of one or two substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -C(=O)-Cy 3 -(C=O)-C 1~4 alkyl-OH, -C(=O)-C 1~4 Alkyl-OC 1~4 Alkyl, -C(=O)-C 1~4 Alkyl-NR 11a R 11b , and C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 9 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 The alkyl group is substituted, and the aromatic ring may optionally have -OH, halo, and C on one or two carbon atoms, each independently. 1~4 (Represents a group consisting of alkyl groups, which consists of a total of one or two substituents selected from the group,) Cy 1 However, at the discretion of choice, -OH, -NH-C(=O)-C 1~4 Alkyl, C 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR9a R 9b , -OH, C 1~4 Alkyl,

[0146] [ka] Furthermore, each independently of Het 3a , Het 6a , Het 6b , and -NR 9a R 9b C substituted with one or two substituents selected from the group consisting of 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) Cy 3 However, C 3~7 Cycloalkyl (in this case, the C 3~7 This represents a cycloalkyl group that is optionally substituted with one, two, or three halo substituents. R 9a and R 9b However, each independently, hydrogen;C 1~4 Alkyl; C 3~6 Cycloalkyl;-C(=O)-C 1~4 Alkyl;-C(=O)-C 3~6 Cycloalkyl;-S(=O)2-C 1~4 Alkyl; Het 5 ;Het 7 ;-C 1~4 Alkyl-R 16 ;-C(=O)-C 1~4 Alkyl-Het 3a ;-C(=O)-R 14 ; Hal, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 3~6 Cycloalkyl; as well as halo, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 1~4 Selected from the group consisting of alkyl groups, R11a , R 11b , R 13a , R 13b , R 15a , R 15b , R 17a , R 17b , R 20a , and R 20b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 11c and R 11d However, each independently, hydrogen, C 1~6 Alkyl and -C(=O)-C 1~4 Selected from the group consisting of alkyl groups, R 10a and R 10b However, each independently, hydrogen, C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 14 However, Het 5a ;Het 7 ;Het 8a ;-OC 1~4 Alkyl;-C(=O)NR 15a R 15b ;-OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halo 3~6 Cycloalkyl; or -OC 1~4 Alkyl, -NR 13a R 13b , halo, cyano, -OH, het 8a , and Cy 1 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 Represents alkyl, R 16 However, -C(=O)-NR 17a R 17b -S(=O)2-C 1~4 Alkyl, Het 5 , Het 7 , or Het 8 [represents] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0147] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y -, -O-, -C(=O)-, -NR q -, or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, cyano, halo, het, -C(=O)-NR xa R xb -S(=O)2-R 18 ,

[0148] [ka] This represents, R 18 However, C 1~6 Alkyl or C 3~6 Represents cycloalkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, Het is a monocyclic 5 or 6-membered aromatic ring containing 1, 2, or 3 nitrogen atoms and optionally a carbonyl moiety (in this case, the monocyclic 5 or 6-membered aromatic ring optionally contains C 1~4 Alkyl, C 3~6 (represented by being substituted with one, two, or three substituents selected from the group consisting of cycloalkyl or cyano) R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6 Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl and NR 11c R 11d (Substituted with 1, 2, or 3 substituents selected from the group consisting of, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, -C 1~4 Alkyl-OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 1b However, it represents hydrogen, F, or Cl. R 2 However, C 1~4 It represents alkyl, and in particular, R 2 However, it represents methyl, R 21 However, hydrogen or -Y a -R 3a This represents, however, R 21 ga-Y a -R 3a When representing -Y a -R 3a and -YR 3 On the condition that one of them is bonded to the nitrogen atom of the ring, Y and Y aHowever, each is independent, covalently bonded or

[0149] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, hydrogen, -OH, C 1~4 Alkyl, -C 1~4 Alkyl-OH, or -C 1~4 Alkyl-OC 1~4 Represents alkyl, R q However, hydrogen or C 1~4 Represents alkyl, R 5 However, hydrogen, C 1~4 Alkyl, or C 3~6 Represents cycloalkyl, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C 1~6 Alkyl; and each independently -C(=O)-NR 10a R 10b , -NR 10c -C(=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, cyano, halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R xc However, Cy 1 , Het 5 , -C 1~6 Alkyl-Cy 1 , -C 1~6 Alkyl-Het3 , -C 1~6 Alkyl-Het 4 , or -C 1~6 Represents alkylphenyl, R xd However, hydrogen; C 1~4 alkyl; or halo, -OH, -OC 1~4 C substituted with one, two, or three substituents selected from the group consisting of alkyl and cyano 1~4 Represents alkyl, or R xc and R xd These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl-S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4Alkyl, -C(=O)-NR 10a R 10b , and -NR 10c -C(=O)-C 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 1~6 Selected from the group consisting of alkyl groups, Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH. , Het 2 However, this represents a C-bonded pyrazolyl or triazolyl, which can be optionally placed on one nitrogen atom, R 6a It may be replaced with, R 6 and R 6a However, each is independent, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-S(=O)2-C 1~4 Alkyl; optional, each independently Het 3 , Het4 , Het 6a , Het 6b Cy 1 -CN, -OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl-C 3~6 Cycloalkyl, -C(=O)-OH, -NR 11a R 11b , and -NH-S(=O)2-C 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 1~6 Alkyl; and optionally, -CN, -OH, -OC, each independently. 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -NH-S(=O)2-C 1~4 Alkyl, and optionally OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl and -NH-S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 3~6 Selected from the group consisting of cycloalkyl groups, R 8 However, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, Halo, Cyano, -NR 11a R 11b , Het 3a , and Het 6a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 , Het 3a , Het 5 , and Het 5aHowever, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline may optionally have a carbon atom on one carbon atom, C 1~4 Alkyl, halo, -OH, -NR 11a R 11b , or substituted with an oxo, and the heterocyclyl optionally has a C on one nitrogen atom. 1~4 Substituted with alkyl , Het 4 and Het 7 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring, or each may independently contain one, two, three, or four heteroatoms selected from O, S, and N in a fused bicyclic carbon bond 9 or 10-membered aromatic ring (in which case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 Alkyl or -(C=O)-OC 1~4 The aromatic ring is substituted, and optionally, on one or two carbon atoms, each independently, -OH, halo, C 1~4 Alkyl, -OC 1~4 Alkyl, -NR 11a R 11b , C 1~4 Alkyl-NR 11a R 11b -NH-C(=O)-C 1~4 Alkyl, cyano, -COOH, -NH-C(=O)-OC 1~4 Alkyl, -NH-C(=O)-Cy 3 -NH-C(=O)-NR 10a R 10b -(C=O)-OC 1~4 Alkyl, -NH-S(=O)2-C 1~4Alkyl, Het 8a , -C 1~4 Alkyl-Het 8a , Het 8b , Het 9 , and -C(=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a , Het 8 , and Het 8a However, each contains independently one N atom and optionally, each independently selected from O, S, and N, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have, on one or two carbon atoms, each independently, a halo, -OH, oxo, or -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 -(C=O)-NR 10a R 10b ,-OC 3~6 Cycloalkyl, -S(=O)2-C 1~4 Alkyl, cyano, C 1~4 Alkyl, -C 1~4 alkyl-OH, -OC 1~4 Alkyl, -O-(C=O)-NR 10a R 10b , and -O-(C=O)-C 1~4 The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by a substituent selected from the group consisting of) Het 6b and Het 8bHowever, each contains independently one N atom and optionally, independently, one or two additional heteroatoms selected from O, S, and N, forming a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have one or two carbon atoms independently of each other C 1~4 Alkyl, -OH, oxo, -(C=O)-NR 10a R 10b -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 , and -OC 1~4 The heterocyclyl is substituted with a total of one or two substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -C(=O)-Cy 3 -(C=O)-C 1~4 alkyl-OH, -C(=O)-C 1~4 Alkyl-OC 1~4 Alkyl, -C(=O)-C 1~4 Alkyl-NR 11a R 11b , and C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 9 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 The alkyl group is substituted, and the aromatic ring may optionally have -OH, halo, and C on one or two carbon atoms, each independently. 1~4 (Represents a group consisting of alkyl groups, which consists of a total of one or two substituents selected from the group,) Cy 1 However, at the discretion of choice, -OH, -NH-C(=O)-C 1~4 Alkyl, C 1~4 Alkyl, -NH-S(=O)2-C 1~4Alkyl, -S(=O)2-C 1~4 Alkyl and -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, C 1~4 Alkyl,

[0150] [ka] Furthermore, each independently of Het 3a , Het 6a , Het 6b , and -NR 9a R 9b C substituted with one or two substituents selected from the group consisting of 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) Cy 3 However, C 3~7 Cycloalkyl (in this case, the C 3~7 This represents a cycloalkyl group that is optionally substituted with one, two, or three halo substituents. R 9a and R 9b However, each independently, hydrogen;C 1~4 Alkyl; C 3~6 Cycloalkyl;-C(=O)-C 1~4 Alkyl;-C(=O)-C 3~6 Cycloalkyl;-S(=O)2-C 1~4 Alkyl; Het 5 ;Het 7 ;-C 1~4 Alkyl-R 16 ;-C(=O)-C1~4 Alkyl-Het 3a ;-C(=O)-R 14 ; Hal, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 3~6 Cycloalkyl; as well as halo, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 1~4 Selected from the group consisting of alkyl groups, R 11a , R 11b , R 13a , R 13b , R 15a , R 15b , R 17a , R 17b , R 20a , and R 20b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 11c and R 11d However, each independently, hydrogen, C 1~6 Alkyl and -C(=O)-C 1~4 Selected from the group consisting of alkyl groups, R 10a and R 10b However, each independently, hydrogen, C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 14 However, Het 5a ;Het 7 ;Het 8a ;-OC 1~4 Alkyl;-C(=O)NR 15a R 15b ;-OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halo 3~6 Cycloalkyl; or -OC 1~4 Alkyl, -NR 13a R 13b, halo, cyano, -OH, het 8a , and Cy 1 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 Represents alkyl, R 16 However, -C(=O)-NR 17a R 17b -S(=O)2-C 1~4 Alkyl, Het 5 , Het 7 , or Het 8 [represents] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0151] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y - or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, halo, -C(=O)-NR xa R xb , or

[0152] [ka] This represents, R 18 However, C 1~6 Alkyl or C 3~6 Represents cycloalkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, R xa and R xb However, each independently, hydrogen, Het 3 , and C 1~6 Alkyl (at this time, optionally, the C 1~6 Alkyl groups are independently -OH and -OC. 1~4(Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups) or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 Alkyl, -OH, and -OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 Alkyl, -OH, and -OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), R 1b However, it represents F, R 2 But, hello, C 1~4 C substituted with alkyl or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, it represents hydrogen, Y is covalent or

[0153] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, it represents hydrogen, R 5However, it represents hydrogen, R 3 and R 4 However, each is independent, Het 1 ;Cy 2 ;C 1~6 alkyl; and each independently of -NR xc R xd , -NR 8a R 8b -CF3, -OH, Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), R 8a and R 8b However, each is independent, C 1~6 alkyl; and one -OC 1~4 C substituted with alkyl 1~6 Selected from the group consisting of alkyl groups, Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of the following, and the heterocyclyl is optionally oxy and -NR on one or two carbon atoms, each independently. 9a R 9b Substituted with a total of one or two substituents selected from the group consisting of , R 6 However, Het 4 -C(=O)-NH-R 8 -S(=O)2-C 1~4 Alkyl, or C 1~6 Represents alkyl, R 8 However, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano 1~6 Represents alkyl, Het 3 However, each independently represents a monocyclic carbon-bonded 4- to 7-membered complete or partially saturated heterocycline containing 1, 2, or 3 heteroatoms selected from O, S, and N. Het 4However, each contains one, two, or three heteroatoms independently selected from O, S, and N in a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, three, or four heteroatoms independently selected from O, S, and N in a fused bicyclic 9- or 10-membered aromatic ring with carbon bonds (in which case, the aromatic ring may optionally contain a total of one or two -(C=O)-NR atoms on one or two carbon atoms). 10a R 10b (represented by being replaced by) Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have a total of one or two -S(=O)2-C atoms on one or two carbon atoms) 1~4 The heterocycline is substituted with alkyl, and optionally, on one nitrogen, it has -C(=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 6b However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 A cycloalkyl group or the carbon bicyclic system is optionally selected, and each is independently R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b ,

[0154] [ka] (represented by being substituted with 1, 2, 3, or 4 substituents selected from the group consisting of) R 9a and R 9b However, each independently, hydrogen, C 1~4 Alkyl, -C(=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 Selected from the group consisting of alkyl groups, R 10a and R 10b However, each independently, hydrogen, C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups. This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0155] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y - or -CR y The dotted line represents Q = -CR y An optional additional bond to form a double bond when representing =, R 1a However, hydrogen, halo, or -C(=O)-NR xa R xb This represents, R xa and R xb However, each independently, hydrogen and C 1~6 Selected from the group consisting of alkyl groups, R 1b However, it represents F, R 2 But, hello, C 1~4 C substituted with alkyl or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, it represents hydrogen, Y is covalent or

[0156] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, it represents hydrogen, R 5 However, it represents hydrogen, R 3 and R 4 However, each is independent, Het 1 ;Cy 2 ;C 1~6 alkyl; and each independently of -NR xc R xd , -NR 8a R 8b , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups) R8a and R 8b However, each is independent, C 1~6 alkyl; and one -OC 1~4 C substituted with alkyl 1~6 Selected from the group consisting of alkyl groups, Het 1 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case, the heterocycline optionally contains R on one nitrogen atom). 6 and -C(=O)-R 8 (represented by a substituent selected from the group consisting of) R 6 However, Het 4 -C(=O)-NH-R 8 , or -S(=O)2-C 1~4 Represents alkyl, R 8 However, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano 1~6 Represents alkyl, Het 4 However, each contains one, two, or three heteroatoms independently selected from O, S, and N in a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, three, or four heteroatoms independently selected from O, S, and N in a fused bicyclic 9- or 10-membered aromatic ring with carbon bonds (in which case, the aromatic ring may optionally contain a total of one or two -(C=O)-NR atoms on one or two carbon atoms). 10a R 10b (represented by being replaced by) Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have a total of one or two -S(=O)2-C atoms on one or two carbon atoms)1~4 The heterocycline is substituted with alkyl, and optionally, on one nitrogen, it has -C(=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 6b However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, each can be chosen independently and R 6 , Het 6a , Het 6b , and -NR 9a R 9b C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 3~7 Represents cycloalkyl, R 9a and R 9b However, each independently, hydrogen, C 1~4 Alkyl, -C(=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 Selected from the group consisting of alkyl groups, R 10a and R 10b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups. This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0157] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xaand R xb However, C 1~6 Represents alkyl, R 1b However, it represents F, R 2 However, Halo or C 1~4 Represents alkyl, R 21 However, it represents hydrogen, Y is covalent or

[0158] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, it represents hydrogen, R 5 However, it represents hydrogen, R 3 However, Het 1 ;Cy 2 ;C 1~6 alkyl; and each independently of -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R 4 However, C 1~6 Alkyl, especially isopropyl, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline optionally contains 1, 2, or 3 -(C=O)-C 1~4 (represented by alkyl substitution) Het 1However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case, the heterocycline optionally contains R on one nitrogen atom). 6 and -C(=O)-R 8 (represented by a substituent selected from the group consisting of) R 6 However, Het 4 or -C(=O)-NH-R 8 This represents, R 8 However, C 1~6 alkyl; or each independently -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano 1~6 Represents alkyl, Het 4 However, each contains one, two, or three heteroatoms independently selected from O, S, and N in a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, three, or four heteroatoms independently selected from O, S, and N in a fused bicyclic 9- or 10-membered aromatic ring with carbon bonds (in which case, the aromatic ring may optionally contain a total of one or two -(C=O)-NR atoms on one or two carbon atoms). 10a R 10b (represented by being replaced by) Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Het 6b However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom)1~4 (represented by alkyl substitution) Cy 2 However, each can be chosen independently and R 6 , Het 6a , Het 6b , and -NR 9a R 9b C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 3~7 Represents cycloalkyl, R 9a and R 9b However, each independently, hydrogen and -S(=O)2-C 1~4 Selected from the group consisting of alkyl groups, R 10a and R 10b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups. This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0159] In particular, the present invention relates to formula (I) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xa and R xb However, C 1~6 Represents alkyl, R 1b However, it represents F, R 2 However, C 1~4 Represents alkyl, R 21 However, it represents hydrogen, Y is covalent or

[0160] [ka] This represents, n1 and n2 are each independently selected from 1 and 2. R y However, it represents hydrogen, R 5 However, it represents hydrogen, R 3 However, Cy 2 ; and each independently -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R 4 However, C 1~6 Alkyl, especially isopropyl, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing, together with the N atom to which they are bonded, one N atom and one additional heteroatom optionally selected from O, S, and N (in which case the heterocycline optionally contains 1, 2, or 3 -(C=O)-C 1~4 (Substituted with alkyl) Het 1 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case, the heterocycline optionally has -C(=O)-R on one nitrogen atom). 8 (represented by being replaced by) R 6 However, -C(=O)-NH-R 8 This represents, R 8 However, C 1~6 Represents alkyl, Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, each can be chosen independently and R 6and Het 6a C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 3~7 [Represents cycloalkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0161] In one embodiment, the present invention relates to formula (I) [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xa and R xb However, C can be optionally substituted with 1, 2, or 3 -OH groups. 1~6 It is alkyl, R 1b However, it represents F, R 2 However, it represents methyl, R 21 However, it represents hydrogen or methyl, Y represents a covalent bond, n1 is 1, n2 is selected from 1 and 2. R y However, it represents hydrogen, R 3 However, each is independent of -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8 Selected from alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline optionally contains 1, 2, or 3 -(C=O)-C1~4 (Substituted with alkyl) Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocyclyl then, at random, has a -C(=O)-R group on one nitrogen atom. 8 The heterocyclyl is substituted, and optionally, one carbon atom is substituted with an oxo. , R 8 However, C 1~6 alkyl; or each independently -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano groups. 1~6 Represents alkyl, Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, you can choose one Het 6a C replaced by 3~7 [Represents cycloalkyl] This relates to the compounds of, and their pharmaceutically acceptable salts and solvates, or any subgroup thereof, and their pharmaceutically acceptable salts and solvates.

[0162] In one embodiment, the present invention relates to formula (I) [wherein Q is -CHR] as referred to in one of the other embodiments. yor -CR y The dotted line represents Q = -CR y This relates to compounds of [where = is an optional additional bond for forming a double bond], as well as their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0163] In one embodiment, the present invention relates to formula (I) [wherein Q is -CHR] as referred to in one of the other embodiments. y This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0164] In one embodiment, the present invention relates to formula (I) [wherein, R 1a However, hydrogen, Het, -C(=O)-NR xa R xb -S(=O)2-R 18 ,

[0165] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0166] In one embodiment, the present invention relates to formula (I) [wherein, R 1a However, Het, -C(=O)-NR xa R xb -S(=O)2-R 18 ,

[0167] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0168] In one embodiment, the present invention relates to formula (I) [wherein, R1a However, -C(=O)-NR xa R xb -S(=O)2-R 18 , or

[0169] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0170] In one embodiment, the present invention relates to formula (I) [wherein, R 1a However, -C(=O)-NR xa R xb , or

[0171] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0172] In one embodiment, the present invention relates to formula (I) [wherein, R 1a However, -C(=O)-NR xa R xb This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0173] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 18 However, C 1~6 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0174] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb However, hydrogen or C 1~6This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0175] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb However, each independently, hydrogen, Het 3 , and C 1~6 Alkyl (at this time, optionally, the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups) or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 Alkyl, -OH, and -OC 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 Alkyl, -OH, and -OC 1~4 This relates to compounds of which are substituted with one, two, or three substituents selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0176] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb However, each independently, hydrogen, Het 3 , and C 1~6 Alkyl (at this time, optionally, the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 This relates to compounds of which are substituted with one, two, or three substituents selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0177] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb However, C 1~6 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0178] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb This relates to compounds of which are combined, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0179] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb This relates to compounds of which are not combined, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0180] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 1b This relates to compounds of F or Cl, as well as their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0181] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 1b This relates to compounds of F, as well as their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0182] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 2 But, hello, C 1~4 C substituted with alkyl or 1, 2, or 3 halo substituents 1~4 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0183] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 2 However, Halo or C 1~4 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0184] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 2 However, C 1~4 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0185] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 2 This relates to compounds of methyl, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0186] In one embodiment, the present invention relates to formula (I) [wherein, R 2 However, R represents methyl, 1a However, -C(=O)-NR xa R xbThis relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0187] In one embodiment, the present invention relates to formula (I) [wherein Y and Y] as referred to in any of the other embodiments. a This relates to compounds that represent covalent bonds, as well as their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0188] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 21 This relates to compounds of hydrogen, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0189] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 21 This relates to compounds of hydrogen or methyl, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0190] In one embodiment, the present invention relates to formula (I) [wherein, R 21 However, it represents hydrogen, This relates to compounds of which Y represents a covalent bond, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0191] In one embodiment, the present invention relates to formula (I) [wherein, R 21 However, it represents hydrogen or methyl, This relates to compounds of which Y represents a covalent bond, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0192] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 21 However, -Y a -R 3aThis relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0193] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 21 However, hydrogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, or halo, -OH, -OC 1~4 Alkyl, -C(=O)-NR 10a R 10b , -NR 10c -C(=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~6 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0194] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 21 However, C 1~6 Alkyl, C 3~6 Cycloalkyl, or halo, -OH, -OC 1~4 Alkyl, -C(=O)-NR 10a R 10b , -NR 10c -C(=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~6 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0195] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 10c However, hydrogen, C 1~4 Alkyl and C 3~6 This relates to compounds selected from the group consisting of cycloalkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0196] In one embodiment, the present invention relates to formula (I) [wherein, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C 1~6 Alkyl; and each independently -C(=O)-NR 10a R 10b -S(=O)2-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, cyano, halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4 Alkyl and -C(=O)NR 10a R 10b C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~6 This relates to compounds selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0197] In one embodiment, the present invention relates to formula (I) [wherein, R 3 , R 3a , and R 4 However, -NR 10c -C(=O)-C 1~4 C substituted with alkyl 1~6 Not alkyl, R 8a and R 8b However, -NR 10c -C(=O)-C 1~4 C substituted with alkyl 1~6 This relates to compounds that are not alkyl, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0198] In some embodiments, the present invention relates to compounds of formula (I) [wherein Y represents a covalent bond] as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0199] In one embodiment, the present invention relates to formula (I) [wherein Y], which is referred to in any of the other embodiments. a This relates to compounds that represent covalent bonds, as well as their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0200] In one embodiment, the present invention relates to formula (I) [wherein Y is,] as referred to in one of the other embodiments.

[0201] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0202] In one embodiment, the present invention relates to formula (I) [wherein Y], which is referred to in any of the other embodiments. a but,

[0203] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0204] In some embodiments, the present invention relates to compounds of formula (I) [wherein n1 represents 1 and n2 represents 2] as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0205] In one embodiment, the present invention relates to formula (I) [wherein, R 4 However, C 1~6 Alkyl, oxetanyl, tetrahydropyranyl,

[0206] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0207] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. y This relates to compounds of hydrogen, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0208] In one embodiment, the present invention relates to formula (I) [wherein, R 4 However, C 1~6 Alkyl, oxetanyl, tetrahydropyranyl,

[0209] [ka] This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0210] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 4 However, C 1~6 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0211] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 4 This relates to compounds of isopropyl, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0212] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 4 However, C 1~8 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0213] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 4 However, C 1~4 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0214] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 5 This relates to compounds of hydrogen, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0215] In one embodiment, the present invention relates to formula (I) [wherein, R 3 and R 4 However, each is independent, Het 1 ;Cy 2 ;C 1~6 alkyl; and each independently of -NR xc R xd , -NR 8a R 8b , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6This relates to compounds selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0216] In one embodiment, the present invention relates to formula (I) [wherein, R 3 However, Het 1 ;Cy 2 ;C 1~6 alkyl; and each independently of -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R 4 However, C 1~6 This relates to alkyl compounds, particularly isopropyl compounds, and their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0217] In one embodiment, the present invention relates to formula (I) [wherein, R 3 However, Cy 2 ; and each independently -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from the group consisting of alkyl groups, R 4 However, C 1~6 This relates to alkyl compounds, particularly isopropyl compounds, and their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0218] In one embodiment, the present invention relates to formula (I) [wherein, R 3 However, Het 1 ;Cy 2 ;C 1~6alkyl; and each independently of -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 This relates to compounds selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0219] In one embodiment, the present invention relates to formula (I) [wherein, R 3 However, Cy 2 ; and each independently -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 This relates to compounds selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0220] In one embodiment, the present invention relates to formula (I) [wherein Cy 2 However, C 3~7 Represents an alkyl or a 5-12 member saturated carbon bicyclic system, (in this case, the C 3~7 A cycloalkyl group or the carbon bicyclic system is optionally selected, and each is independently R 6 , -NR 9a R 9b This relates to compounds of which are substituted with 1, 2, 3, or 4 substituents selected from the group consisting of -OH, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0221] In one embodiment, the present invention relates to formula (I) [wherein, R xc and R xdThese combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 This relates to compounds of which are substituted with one, two, or three substituents selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0222] In one embodiment, the present invention relates to formula (I) [wherein, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain -(C=O)-C 1~4 Alkyl and -S(=O)2-C 1~4 This relates to compounds of which are substituted with one, two, or three substituents selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0223] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xc and R xd This relates to compounds of which are combined, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0224] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xc and R xd This relates to compounds of which are not combined, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0225] In some embodiments, the present invention relates to compounds of formula (I) [wherein the fully saturated or partially saturated heterocyclyl group is limited to a fully saturated heterocyclyl group] as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0226] In one embodiment, the present invention relates to formula (I) [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R 1b However, it represents F, R 2 This relates to compounds of methyl, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0227] In one embodiment, the present invention relates to formula (I) [wherein, R 8a and R 8b However, each is independent, C 1~6 alkyl; and one -OC 1~4 C substituted with alkyl 1~6This relates to compounds selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0228] In one embodiment, the present invention relates to formula (I) [wherein, Het 1 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have R on one nitrogen atom. 6 and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of the following, and the heterocyclyl is optionally oxy and -NR on one or two carbon atoms, each independently. 9a R 9b This relates to compounds of [represented by] (substituted with a total of one or two substituents selected from the group consisting of ), as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0229] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 6 However, Het 4 or -C(=O)-NH-R 8 This relates to compounds of [represented by], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0230] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 8 However, C 1~6 alkyl; or each independently -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano 1~6This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0231] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 8 However, C 1~6 This relates to compounds of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0232] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 8 This relates to compounds of methyl, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0233] In one embodiment, the present invention relates to formula (I) [wherein, Het 4 However, each contains one, two, or three heteroatoms independently selected from O, S, and N in a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, three, or four heteroatoms independently selected from O, S, and N in a fused bicyclic 9- or 10-membered aromatic ring with carbon bonds (in which case, the aromatic ring may optionally contain a total of one or two -(C=O)-NR atoms on one or two carbon atoms). 10a R 10b This relates to compounds of [represented by (substituted with)], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0234] In one embodiment, the present invention relates to formula (I) [wherein, Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4This relates to compounds of [represented by alkyl substitution], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0235] In one embodiment, the present invention relates to formula (I) [wherein, Het 6b However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 This relates to compounds of [represented by alkyl substitution], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0236] In one embodiment, the present invention relates to formula (I) [wherein, Cy 2 However, C 3~7 Cycloalkyl or 5-12 membered saturated carbon bicyclic systems (At this time, C 3~7 A cycloalkyl group or the carbon bicyclic system is optionally selected, and each is independently R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b ,

[0237] [ka] This relates to compounds of [represented by] (substituted with 1, 2, 3, or 4 substituents selected from the group consisting of ), as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0238] In one embodiment, the present invention relates to formula (I) [wherein, Cy 2However, each can be chosen independently and R 6 , Het 6a , Het 6b , -NR 9a R 9b ,

[0239] [ka] This relates to compounds of [represented by] (substituted with 1, 2, 3, or 4 substituents selected from the group consisting of ), as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0240] In one embodiment, the present invention relates to formula (I) [wherein, Cy 2 However, each can be chosen independently and R 6 , Het 6a , Het 6b , and -NR 9a R 9b C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 3~7 This relates to compounds of the cycloalkyl group, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0241] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 9a and R 9b However, each independently, hydrogen and -S(=O)2-C 1~4 This relates to compounds selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0242] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. 10a and R 10b However, each independently, hydrogen and C 1~4 This relates to compounds selected from the group consisting of alkyl groups, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0243] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb The present invention relates to compounds of [where together they form a monocyclic heterocycline, they represent 1-pyrrolidinil or 1-piperidinil, each optionally substituted as defined in any of the other embodiments], as well as their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0244] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xa and R xb When they come together to form a bicyclic heterocycline, they are

[0245] [ka] This relates to compounds of [represented by, each optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0246] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xc and R xd The present invention relates to compounds of [where these compounds together form a monocyclic heterocycline, they represent 1-pyrrolidinyl, 1-piperidinyl, or 1-piperazinyl, each optionally substituted as defined in any of the other embodiments], as well as their pharmaceutically acceptable salts and solvates, or any subgroup thereof.

[0247] In one embodiment, the present invention relates to formula (I) [wherein R], which is mentioned in any of the other embodiments. xc and R xd When they come together to form a bicyclic heterocycline, they are

[0248] [ka] This relates to compounds of [represented by and optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0249] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 1 but,

[0250] [ka] This relates to compounds of [represented by and optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0251] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 1 but,

[0252] [ka] This represents, and optionally, on the nitrogen atom, -C(=O)-C 1~4 This relates to compounds [substituted with alkyl], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0253] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 1 but,

[0254] [ka] This represents -C(=O)-C on the nitrogen atom. 1~4 This relates to compounds [substituted with alkyl], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0255] In one embodiment, the present invention relates to formula (I) [wherein, Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a condensed or spironicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH ru] This relates to compounds thereof, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0256] In one embodiment, the present invention relates to formula (I) [wherein, Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a condensed or spironicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of the following, and the heterocyclyl is optionally oxy and -NR on one or two carbon atoms, each independently. 9a R 9b Substituted with a total of one or two substituents selected from the group consisting of ru] This relates to compounds thereof, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0257] In one embodiment, the present invention relates to formula (I) [wherein, Het 1 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), and the heterocycline optionally has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b This relates to compounds of [represented by , and -OH, which are substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0258] In one embodiment, the present invention relates to formula (I) [wherein, Het 1However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), and the heterocycline optionally has R on one nitrogen atom. 6 and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of the following, and the heterocyclyl is optionally independently oxo and -NR on one or two carbon atoms. 9a R 9b This relates to compounds of [represented by] (substituted with a total of one or two substituents selected from the group consisting of ), as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0259] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 3 but,

[0260] [ka] This relates to compounds of [represented by and optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0261] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 4 The present invention relates to compounds of which represent a C-bonded pyrazinyl, which is optionally substituted as defined in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0262] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 6a but,

[0263] [ka] This relates to compounds of [represented by and optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0264] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 6a but,

[0265] [ka] This relates to compounds of [represented by and optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0266] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 6a but,

[0267] [ka] This represents -C(=O)-C on the nitrogen atom. 1~4 This relates to compounds [substituted with alkyl], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0268] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments. 6b but,

[0269] [ka] This relates to compounds of [represented by and optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0270] In one embodiment, the present invention relates to formula (I) [wherein Het], which is referred to in any of the other embodiments.6b but,

[0271] [ka] This represents -C(=O)-C on the nitrogen atom. 1~4 This relates to compounds [substituted with alkyl], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0272] In one embodiment, the present invention relates to formula (I) [wherein Cy 2 However, C 3~7 Cycloalkyl,

[0273] [ka] This relates to compounds of [represented by and optionally substituted as defined in any of the other embodiments], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0274] In one embodiment, the present invention relates to formula (I) [wherein C], which is mentioned in any of the other embodiments. 1~8 Alkyl is C 1~6 Limited to alkyl groups, especially C 1~8 Alkyl is C 1~4 This relates to compounds [limited to alkyl groups], as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0275] In one embodiment, the present invention relates to formula (I) [wherein -YR] as referred to in any of the other embodiments. 3 This relates to compounds of which are bonded to the nitrogen atom of the ring, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0276] In one embodiment, the present invention relates to formula (I) [wherein, R 21 However, it is hydrogen, -YR 3This relates to compounds of which are bonded to the nitrogen atom of the ring, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof.

[0277] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein a compound of formula (I) is of formula (Ix):

[0278] [ka] The compounds are limited to those of the formula [wherein the variable element is defined for the compounds of formula (I) or any subgroup thereof as referred to in any of the other embodiments].

[0279] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein a compound of formula (I) is defined as formula (I-x1):

[0280] [ka] The compounds are limited to those of the formula [wherein the variable element is defined for the compounds of formula (I) or any subgroup thereof as referred to in any of the other embodiments].

[0281] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein a compound of formula (I) is of formula (I-x2):

[0282] [ka] [In the formula, Q is -CHR y -, -O-, -C(=O)-, or -NR q- represents and other variable elements are limited to compounds of formula (I) as defined for any subgroup thereof as mentioned in any of the other embodiments.

[0283] In particular, the present invention relates to formula (I-x2) as defined herein [wherein, Q is -CHR y -, -O-, -C(=O)-, or -NR q - represents, R 1a However, hydrogen, cyano, halo, het, -C(=O)-NR xa R xb -S(=O)2-R 18 -C(=O)-OC 1~4 Alkyl-NR 22a R 22b -C(=O)-OC 1~4 Alkyl,

[0284] [ka] This represents, R 18 However, C 1~6 Alkyl or C 3~6 Represents cycloalkyl, R 19 However, hydrogen or C 1~6 Represents alkyl, or R 18 and R 19 These combine to form -(CH2)3-, -(CH2)4-, or -(CH2)5-, Het is a monocyclic 5 or 6-membered aromatic ring containing 1, 2, or 3 O-, S-, or N- atoms and optionally a carbonyl moiety (in this case, the monocyclic 5 or 6-membered aromatic ring optionally contains C 1~4 Alkyl, C 3~6 (represented by being substituted with one, two, or three substituents selected from the group consisting of cycloalkyl or cyano) R xa and R xb However, each independently, hydrogen, Het 3 , C 3~6Cycloalkyl, and C 1~6 Alkyl (at this time, optionally, the C 3~6 Cycloalkyl and the C 1~6 Alkyl groups are independently -OH and -OC. 1~4 Alkyl, -C 1~4 alkyl-OH, halo, CF3, C 3~6 Cycloalkyl, Het 3 , and NR 11c R 11d (Substituted with 1, 2, or 3 substituents selected from the group consisting of, or R xa and R xb These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, cyano, halo, and OR 23 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), or R xa and R xb These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain C 1~4 alkyl, halo, -OH, -OC 1~4 Alkyl, cyano, and each independently halo and OR 23 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups), R 23 However, C is substituted with hydrogen or, optionally, one, two, or three halos. 1~4 Represents alkyl, R 1b However, hydrogen, F, Cl, or -OC 1~4 Represents alkyl, R 2 But, hello, C 3~6 Cycloalkyl, C 1~4 Alkyl, -OC 1~4 C substituted with alkyl, cyano, or 1, 2, or 3 halo substituents 1~4 Represents alkyl, R 21 However, hydrogen or -Y a -R 3a This represents, Y and Y a However, each is independent, covalently bonded or

[0285] [ka] This represents, n1 is selected from 1 and 2. n2 is selected from 1, 2, 3, and 4. R y However, hydrogen, -OH, C 1~4 Alkyl, -C 1~4 Alkyl-OH, or -C 1~4 Alkyl-OC 1~4 Represents alkyl, R q However, hydrogen or C 1~4 Represents alkyl, R 5 However, hydrogen, C 1~4 Alkyl, or C 3~6 Represents cycloalkyl, R 3 , R 3a , and R 4 However, each is independent, Het 1 ;Het 2 ;Cy 2 ;C 1~8 Alkyl; and each independently -C(=O)-NR 10a R 10b-C(=O)-Het 6a , -C(=O)-Het 6b , -NR 10c -C(=O)-C 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl, -NR xc R xd , -NR 8a R 8b -CF3, cyano, halo, -OH, -OC 1~4 Alkyl, Het 1 , Het 2 Ar 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8 Selected from the group consisting of alkyl groups, R xc However, Cy 1 , Het 5 , -C 1~6 Alkyl-Cy 1 , -C 1~6 Alkyl-Het 3 , -C 1~6 Alkyl-Het 4 , or -C 1~6 Represents alkylphenyl, R xd However, hydrogen; C 1~4 alkyl; or halo, -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano 1~4 Represents alkyl, or R xc and R xd These combine to form a 4-7 member monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally contain halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl, -S(=O)2-C 1~4(Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) or R xc and R xd These combine to form a 6-11 membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally be halo, -OH, or -OC 1~4 Alkyl, -(C=O)-C 1~4 Alkyl-S(=O)2-C 1~4 (Substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and cyano) R 8a and R 8b However, each independently, hydrogen;C 1~6 Alkyl;-(C=O)-C 1~4 Alkyl; and each independently -OH, cyano, halo, and -S(=O)2-C 1~4 Alkyl, -OC 1~4 Alkyl, -C(=O)-NR 10a R 10b , and -NR 10c -C(=O)-C 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 1~6 Selected from the group consisting of alkyl groups, Ar 1 However, each can be chosen independently of C 1~4 alkyl, halo, -OC 1~4 Alkyl, -CF3, -OH, -S(=O)2-C 1~4 Alkyl and -C(=O)-NR 10a R 10b Represents phenyl substituted with one, two, or three substituents selected from the group consisting of the following: Het 1However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline, at its discretion, has R on one nitrogen atom. 6 -C(=O)-Cy 1 , and -C(=O)-R 8 The heterocyclyl is substituted with substituents selected from the group consisting of, and the heterocyclyl may optionally have one or two carbon atoms independently each containing a halo, R 6 , Het 6a , Het 6b , C 1~4 Alkyl, oxo, -NR 9a R 9b Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of , and -OH. , Het 2 However, this represents a C-bonded pyrazolyl, 1,2,4-oxadiazolyl, pyridazinyl, or triazolyl, and this can be optionally configured with R on one nitrogen atom. 6a It may be replaced with, R 6 and R 6a However, each is independent, Het 3 ;Het 4 ;-C(=O)-NH-Cy 1 ;-C(=O)-NH-R 8 ;-C(=O)-Het 6a ;-C(=O)-NR 10d R 10e ;-C(=O)-OC 1~4 Alkyl;-S(=O)2-C 1~4 Alkyl; optional, each independently Het 3 , Het 4 , Het 6a , Het 6b Cy 1-CN, -OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-N(C 1~4 Alkyl)2,-C(=O)-NH-C 1~4 Alkyl-C 3~6 Cycloalkyl, -C(=O)-OH, -NR 11a R 11b , and -NH-S(=O)2-C 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 1~6 Alkyl; and optionally, -CN, -OH, -OC, each independently. 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl, -C(=O)-N(C 1~4 Alkyl)2,-NH-S(=O)2-C 1~4 Alkyl, and optionally OH, -OC 1~4 Alkyl, -C(=O)-NH-C 1~4 Alkyl and -NH-S(=O)2-C 1~4 C substituted with one substituent selected from the group consisting of alkyl groups 1~4 C substituted with one or two substituents selected from the group consisting of alkyl groups 3~6 Selected from the group consisting of cycloalkyl groups, R 8 However, hydrogen, -OC 1~6 Alkyl, C 1~6 Alkyl, or each independently -OH, -OC 1~4 Alkyl, Halo, Cyano, -NR 11a R 11b -S(=O)2-C 1~4 Alkyl, Het 3a , and Het 6a C substituted with 1, 2, or 3 substituents selected from 1~6 Represents alkyl, Het 3 , Het 3a , Het 5 , and Het 5aHowever, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocycline may optionally have a carbon atom on one carbon atom, C 1~4 Alkyl, halo, -OH, -NR 11a R 11b , or substituted with an oxo, and the heterocyclyl optionally has a C on one nitrogen atom. 1~4 Alkyl or -(C=O)-C 1~4 Substituted with alkyl , Het 4 and Het 7 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N in a monocyclic carbon bond 5 or 6-membered aromatic ring, or each may independently contain one, two, three, or four heteroatoms selected from O, S, and N in a fused bicyclic carbon bond 9 or 10-membered aromatic ring (in which case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 Alkyl or -(C=O)-OC 1~4 The aromatic ring is substituted, and optionally, on one or two carbon atoms, each independently, -OH, halo, C 1~4 Alkyl, -OC 1~4 Alkyl, -NR 11a R 11b , C 1~4 Alkyl-NR 11a R 11b -NH-C(=O)-C 1~4 Alkyl, cyano, -COOH, -NH-C(=O)-OC 1~4 Alkyl, -NH-C(=O)-Cy 3 -NH-C(=O)-NR 10a R 10b -(C=O)-OC 1~4Alkyl, -NH-S(=O)2-C 1~4 Alkyl, Het 8a , -C 1~4 Alkyl-Het 8a , Het 8b , Het 9 , and -C(=O)-NR 10a R 10b (represented by being substituted with a total of 1 or 2 substituents selected from the group consisting of) Het 6a , Het 8 , and Het 8a However, each contains independently one N atom and optionally, each independently selected from O, S, and N, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have, on one or two carbon atoms, each independently, a halo, -OH, oxo, or -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 -(C=O)-NR 10a R 10b ,-OC 3~6 Cycloalkyl, -S(=O)2-C 1~4 Alkyl, cyano, C 1~4 Alkyl, -C 1~4 alkyl-OH, -OC 1~4 Alkyl, -O-(C=O)-NR 10a R 10b , and -O-(C=O)-C 1~4 The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -S(=O)2-C 1~4 Alkyl and -(C=O)-NR 10a R 10b (represented by a substituent selected from the group consisting of) Het 6b and Het 8bHowever, each contains independently one N atom and optionally, independently, one or two additional heteroatoms selected from O, S, and N, forming a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have one or two carbon atoms independently of each other C 1~4 Alkyl, -OH, oxo, -(C=O)-NR 10a R 10b -NH-C(=O)-C 1~4 Alkyl, -NH-C(=O)-Cy 3 , and -OC 1~4 The heterocyclyl is substituted with a total of one or two substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. 1~4 Alkyl, -C(=O)-Cy 3 -(C=O)-C 1~4 alkyl-OH, -C(=O)-C 1~4 Alkyl-OC 1~4 Alkyl, -C(=O)-C 1~4 Alkyl-NR 11a R 11b , and C 1~4 (Represents substitution with substituents selected from the group consisting of alkyl groups), Het 9 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally have a carbon atom on one nitrogen atom). 1~4 The alkyl group is substituted, and the aromatic ring may optionally have -OH, halo, and C on one or two carbon atoms, each independently. 1~4 (Represents a group consisting of alkyl groups, which consists of a total of one or two substituents selected from the group,) Cy 1 However, at the discretion of choice, -OH, -NH-C(=O)-C 1~4 Alkyl, C 1~4 Alkyl, -NH-S(=O)2-C 1~4Alkyl, -S(=O)2-C 1~4 Alkyl and -OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl groups 3~6 Represents cycloalkyl, Cy 2 However, C 3~7 Cycloalkyl or 5-12 member saturated carbon bicyclic systems (in this case, the C 3~7 Cycloalkyl or the carbon bicyclic system may be optionally and independently halo, R 6 -C(=O)-Het 6a , Het 6a , Het 6b , -NR 9a R 9b , -OH, C 1~4 Alkyl, -OC 1~4 Alkyl, cyano,

[0286] [ka] Furthermore, each independently of Het 3a , Het 6a , Het 6b , and -NR 9a R 9b C substituted with one or two substituents selected from the group consisting of 1~4 (Represents a molecule substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups.) Cy 3 However, C 3~7 Cycloalkyl (in this case, the C 3~7 This represents a cycloalkyl group that is optionally substituted with one, two, or three halo substituents. R 9a and R 9b However, each independently, hydrogen;C 1~4 Alkyl; C 3~6 Cycloalkyl;-C(=O)-C 1~4 Alkyl;-C(=O)-C 3~6 Cycloalkyl;-S(=O)2-C 1~4 Alkyl; Het 5 ;Het 7 ;-C 1~4 Alkyl-R16 ;-C(=O)-C 1~4 Alkyl-Het 3a ;-C(=O)-R 14 ; Hal, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 3~6 Cycloalkyl; as well as halo, -OH, -OC 1~4 Alkyl, -NR 11a R 11b C substituted with 1, 2, or 3 substituents selected from the group consisting of , and cyano 1~4 Selected from the group consisting of alkyl groups, R 11a , R 11b , R 13a , R 13b , R 15a , R 15b , R 17a , R 17b , R 20a , R 20b , R 22a , and R 22b However, each independently, hydrogen and C 1~4 Selected from the group consisting of alkyl groups, R 11c and R 11d However, each independently, hydrogen, C 1~6 Alkyl and -C(=O)-C 1~4 Selected from the group consisting of alkyl groups, R 10a , R 10b , and R 10c However, each independently, hydrogen, C 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 10d and R 10e However, each is independent, C 1~4 Alkyl, -OC 1~4 Alkyl and C 3~6 Selected from the group consisting of cycloalkyl groups, R 14 However, Het 5a ;Het 7 ;Het8a ;-OC 1~4 Alkyl;-C(=O)NR 15a R 15b ;-OC 1~4 C substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halo 3~6 Cycloalkyl; or -OC 1~4 Alkyl, -NR 13a R 13b , halo, cyano, -OH, het 8a , and Cy 1 C substituted with 1, 2, or 3 substituents selected from the group consisting of 1~4 Represents alkyl, R 16 However, -C(=O)-NR 17a R 17b -S(=O)2-C 1~4 Alkyl, Het 5 , Het 7 , or Het 8 [represents] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0287] In particular, the present invention relates to formula (I-x2) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xa and R xb However, C can be optionally substituted with 1, 2, or 3 -OH groups. 1~6 It is alkyl, R 1b However, it represents F, R 2 However, it represents methyl, R 21 However, it represents hydrogen or methyl, Y is covalent or

[0288] [ka] This represents, R 5 However, it represents hydrogen, n1 is 1, n2 is selected from 1 and 2. R y However, it represents hydrogen, R 3 and R 4 However, each independently of Het 1 Cy 2 , and each independently -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8 Selected from alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline optionally contains 1, 2, or 3 -(C=O)-C 1~4 (Substituted with alkyl) Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocyclyl then, at random, has a -C(=O)-R group on one nitrogen atom. 8 The heterocyclyl is substituted, and optionally, one carbon atom is substituted with an oxo. , R 8 However, C 1~6alkyl; or each independently -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano groups. 1~6 Represents alkyl, Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, optionally, one Het 6a C replaced by 3~7 [Represents cycloalkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0289] In particular, the present invention relates to formula (I-x2) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xa and R xb However, C can be optionally substituted with 1, 2, or 3 -OH groups. 1~6 It is alkyl, R 1b However, it represents F, R 2 However, it represents methyl, R 21 However, it represents hydrogen or methyl, Y is covalent or

[0290] [ka] This represents, R 5 However, it represents hydrogen, n1 is 1, n2 is selected from 1 and 2. R y However, it represents hydrogen, R 3 and R 4 However, each independently of Het 1 Cy 2 , and each independently -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~6 Selected from alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline optionally contains 1, 2, or 3 -(C=O)-C 1~4 (Substituted with alkyl) Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocyclyl then, at random, has a -C(=O)-R group on one nitrogen atom. 8 The heterocyclyl is substituted, and optionally, one carbon atom is substituted with an oxo. , R 8 However, C 1~6 alkyl; or each independently -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano groups. 1~6Represents alkyl, Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, you can choose one Het 6a C replaced by 3~7 [Represents cycloalkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0291] In particular, the present invention relates to formula (I-x2) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xa and R xb However, C can be optionally substituted with 1, 2, or 3 -OH groups. 1~6 It is alkyl, R 1b However, it represents F, R 2 However, it represents methyl, R 21 However, it represents hydrogen or methyl, Y represents a covalent bond, n1 is 1, n2 is selected from 1 and 2. R y However, it represents hydrogen, R 3 However, each is independent of -NR xc R xd , Het 1 , and Cy 2 C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of 1~8Selected from alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline optionally contains 1, 2, or 3 -(C=O)-C 1~4 (Substituted with alkyl) Het 1 However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocyclyl then, at random, has a -C(=O)-R group on one nitrogen atom. 8 The heterocyclyl is substituted, and optionally, one carbon atom is substituted with an oxo. , R 8 However, C 1~6 alkyl; or each independently -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano groups. 1~6 Represents alkyl, Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, you can choose one Het6a C replaced by 3~7 [Represents cycloalkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0292] In particular, the present invention relates to formula (I-x2) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xa and R xb However, C 1~6 It is alkyl, R 1b However, it represents F, R 2 However, it represents methyl, R 21 However, it represents hydrogen, Y represents a covalent bond, n1 is 1, n2 is selected from 1 and 2. R y However, it represents hydrogen, R 3 However, -NR xc R xd , Het 1 , and Cy 2 C substituted with one substituent selected from the group consisting of 1~8 Selected from alkyl groups, R xc and R xd These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and, optionally selected from O, S, and N, along with the N atom to which they are bonded (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline optionally contains 1, 2, or 3 -(C=O)-C 1~4 (Substituted with alkyl) Het 1However, each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4-7 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2), or each may independently contain one, two, or three heteroatoms selected from O, S, and N, forming a bicyclic 6-11 member complete or partially saturated heterocycline with a carbon bond (in which case the S atom may be substituted to form S(=O) or S(=O)2). i) represents The heterocyclyl then, at random, has a -C(=O)-R group on one nitrogen atom. 8 Replaced by , R 8 However, C 1~6 alkyl; or each independently -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano groups. 1~6 Represents alkyl, Het 6a However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-C on one nitrogen atom) 1~4 (represented by alkyl substitution) Cy 2 However, you can choose one Het 6a C replaced by 3~7 [Represents cycloalkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0293] In particular, the present invention relates to formula (I-x2) as defined herein [wherein, Q is -CHR y - represents, R 1a However, -C(=O)-NR xa R xb This represents, R xa and Rxb However, C 1~6 It is alkyl, R 1b However, it represents F, R 2 However, it represents methyl, R 21 However, it represents hydrogen, Y represents a covalent bond, n1 is 1, n2 is selected from 1 and 2. R y However, it represents hydrogen, R 3 However, one Het 1 C replaced by 1~4 Selected from alkyl groups, Het 1 However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom may be substituted to form S(=O) or S(=O)2, and the heterocycline may optionally have -C(=O)-R on one nitrogen atom). 8 (represented by being replaced by) R 8 However, C 1~6 alkyl; or each independently -OH, -OC 1~4 C substituted with 1, 2, or 3 substituents selected from alkyl and cyano groups. 1~6 [Represents alkyl] This invention relates to compounds, their tautomers and stereoisomers, and their pharmaceutically acceptable salts and solvates.

[0294] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein a compound of formula (I) is of formula (Iy):

[0295] [ka] The compounds are limited to those of the formula [wherein the variable element is defined for the compounds of formula (I) or any subgroup thereof as referred to in any of the other embodiments].

[0296] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein the compound of formula (I) is of formula (I-y1):

[0297] [ka] The compounds are limited to those of the formula [wherein the variable element is defined for the compounds of formula (I) or any subgroup thereof as referred to in any of the other embodiments].

[0298] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein a compound of formula (I) is of formula (Iz):

[0299] [ka] The compounds are limited to those of the formula [wherein the variable element is defined for the compounds of formula (I) or any subgroup thereof as referred to in any of the other embodiments].

[0300] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein a compound of formula (I) is of formula (I-z1):

[0301] [ka] The compounds are limited to those of the formula [wherein the variable element is defined for the compounds of formula (I) or any subgroup thereof as referred to in any of the other embodiments].

[0302] In one embodiment, the present invention relates to a compound of formula (I) as referred to in any of the other embodiments, as well as pharmaceutically acceptable salts and solvates thereof, or any subgroup thereof, wherein a compound of formula (I) is of formula (Iq):

[0303] [ka] The compounds are limited to those of the formula [wherein the variable element is defined for the compounds of formula (I) or any subgroup thereof as referred to in any of the other embodiments].

[0304] In one embodiment, the present invention relates to a subgroup of formula (I) defined in a general reaction scheme.

[0305] In one embodiment, the compound of formula (I) is the illustrated compound, Its tautomers and stereoisomers, The free base, any pharmaceutically acceptable salt, and any solvate thereof are selected from the group.

[0306] In one embodiment, the compound of formula (I) is selected from the group consisting of compounds 4, 8, 8a, 9a, 10, 12, 18a, 18b, 20, 27a, 27d, 32a, 34a, 38b, 43, 51, 51a, 59, 60, 115, 117a, 125, 140, 157, 159, 169a, 207, 228, 258, 262, and 365b.

[0307] In one embodiment, the compounds of formula (I) are compounds 4, 8, 8a, 9a, 10, 12, 18a, 18b, 20, 27a, 27d, 32a, 34a, 38b, 43, 51, 51a, 59, 60, 115, 117a, 125, 140, 157, 159, 169a, 207, 228, 258, 262, and 365b; Its tautomers and stereoisomers, The free base, any pharmaceutically acceptable salt, and any solvate thereof are selected from the group.

[0308] The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of formula (I) is selected from the group consisting of any of the exemplified compounds.

[0309] The present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of formula (I) is an example of a compound. Its tautomers and stereoisomers, The invention also relates to pharmaceutical compositions selected from the group consisting of the free base, any pharmaceutically acceptable salt, and the solvate thereof.

[0310] The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of formula (I) is selected from the group consisting of compounds 4, 8, 8a, 9a, 10, 12, 18a, 18b, 20, 27a, 27d, 32a, 34a, 38b, 43, 51, 51a, 59, 60, 115, 117a, 125, 140, 157, 159, 169a, 207, 228, 258, 262, and 365b.

[0311] The present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of formula (I) is compound 4, 8, 8a, 9a, 10, 12, 18a, 18b, 20, 27a, 27d, 32a, 34a, 38b, 43, 51, 51a, 59, 60, 115, 117a, 125, 140, 157, 159, 169a, 207, 228, 258, 262, and 365b; Its tautomers and stereoisomers, The invention also relates to pharmaceutical compositions selected from the group consisting of the free base, any pharmaceutically acceptable salt, and the solvate thereof.

[0312] In certain embodiments, the solvate is a hydrate. In certain embodiments, the pharmaceutically acceptable salt is an HCl salt. In certain embodiments, the compound is an HCl salt hydrate.

[0313] In one embodiment, the compound of formula (I) is

[0314] [ka] or its pharmaceutically acceptable salts or solvates; specifically, HCl salts, solvates; more specifically, HCl salts, hydrates; more specifically, monoHCl salts, hydrates; and even more specifically, monoHCl salts, trihydrates.

[0315] All possible combinations of the embodiments described above are considered to be included within the scope of the present invention.

[0316] Any aspects and embodiments of the present invention described herein with respect to compounds of formula (I) listed herein also apply to compounds of formula (A).

[0317] In some embodiments, the present invention also relates to pharmaceutical compositions selected from the group consisting of any of the intermediates described herein, their tautomers and stereoisomers, and their free bases, any pharmaceutically acceptable salts, and solvates.

[0318] Method for preparing the compound of formula (I) In this section, unless the context indicates otherwise, references to formula (I) in all other sections also include all other subgroups and their embodiments as defined herein.

[0319] The following describes the general preparation of some typical examples of the compound of formula (I), in which specific examples they are prepared from starting materials that are either commercially available or prepared by standard synthesis processes commonly used by those skilled in the field of organic chemistry. The following schemes are merely illustrative examples of the present invention and do not limit the present invention in any way.

[0320] Alternatively, the compounds of the present invention may also be prepared by similar reaction protocols, such as those described in the general scheme below, in combination with standard synthesis processes commonly used by those skilled in the art.

[0321] Those skilled in the art will understand that in the reactions described in the scheme, although not always explicitly stated, it may be necessary to protect reactive functional groups (e.g., hydroxy, amino, or carboxyl groups) if they are desirable in the final product to avoid undesirable involvement in the reaction. Generally, conventional protecting groups (PGs) can be used according to standard techniques. Protecting groups can be removed at a convenient subsequent step using methods well known in the art.

[0322] Those skilled in the art will understand that in the reactions described in the scheme, it may be recommended or necessary to carry out the reactions under an inert atmosphere, such as an N2 gas atmosphere.

[0323] It will be apparent to those skilled in the art that cooling of the reaction mixture may be necessary before the reaction (for example, a series of operations necessary to isolate and purify the products of a chemical reaction, such as quenching, column chromatography, and extraction).

[0324] Those skilled in the art will understand that heating a reaction mixture under stirring can enhance the reaction outcome. In some reactions, microwave heating can be used instead of conventional heating to shorten the overall reaction time.

[0325] Those skilled in the art will understand that another series of chemical reactions shown in the following scheme can also yield the desired compound of formula (I).

[0326] Those skilled in the art will understand that the intermediates and final compounds shown in the following scheme can be further functionalized according to methods well known to those skilled in the art. The intermediates and compounds described herein can be isolated in free form or as salts or solvates thereof. The intermediates and compounds described herein can be synthesized in the form of a mixture of tautomers and stereoisomers, which can be separated from each other according to decomposition procedures known in the art.

[0327] General synthesis scheme All abbreviations used in the general scheme are as defined below or in the table in the Examples section. Variable elements are as defined in the range or as specifically defined in the general scheme. If a compound / intermediate in the following scheme contains a double bond, the substituent may be in an E configuration, a Z configuration, or a mixture thereof.

[0328] Scheme 1 Generally, compounds of formula (I-aa) can be prepared according to the following reaction scheme 1. In scheme 1, PG represents a suitable protecting group such as tert-butyloxycarbonyl, 9-fluorenylmethoxycarbonyl, or benzyl, LG is a leaving group such as chloro, bromo, iodine, or tosylate, or mesylate, or triflate, and all other variable elements are defined according to the scope of the present invention.

[0329] [ka]

[0330] In Scheme 1, the following reaction conditions apply: Step 1: In the case of PG=Boc, in a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable acid, such as a protic acid such as trifluoroacetic acid (TFA) or hydrochloric acid, and in a suitable solvent such as dichloromethane (DCM) or 1,4-dioxane; Alternatively, if PG = 9-fluorenylmethoxycarbonyl, it is prepared at a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable base such as piperidine, and in a suitable solvent such as dichloromethane (DCM); Alternatively, if PG = benzyl, it can be measured at a suitable temperature such as room temperature, in the presence of a suitable heterogeneous catalyst such as palladium on charcoal (Pd / C), in a common solvent such as methanol, ethanol, or THF, under a hydrogen pressure such as 1-3 bar, and optionally in the presence of a base such as triethylamine; Step 2: For reductive amination reactions using aldehydes or ketones: at a suitable temperature in the range of room temperature to 70°C, in the presence of a suitable reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, in a suitable solvent such as methanol, dichloromethane, or 1,2-dichloroethane, and optionally in the presence of zinc chloride, sodium acetate, or acetic acid; LG-YR 3 For alkylation reactions using: for example, at a suitable temperature such as room temperature, in the presence of a suitable deprotonating agent such as sodium hydride or potassium carbonate, or an amine base such as triethylamine, in a suitable aprotic solvent such as dimethylformamide, dimethyl sulfoxide, or acetonitrile.

[0331] Scheme 2 In general, equation (I) [where Q is -O-, -NR] q Compounds of the form [limited to -] can be prepared via an intermediate of formula (VIc). The intermediate of formula (VIc) can be prepared according to the following reaction scheme 2. In scheme 2, PG represents a suitable protecting group such as tert-butoxycarbonyl, and all other variable elements are defined according to the scope of the present invention.

[0332] [ka]

[0333] In Scheme 2, the following reaction conditions apply: Step 1: In a suitable temperature in the range of 100°C to 140°C, in the presence of a suitable base such as potassium tert-butoxide or potassium phosphate, in the presence of a suitable catalyst such as palladium acetate (Pd(OAc)2), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3), or [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2), in the presence of a suitable ligand such as 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos), in a suitable solvent such as dioxane or dimethylformamide.

[0334] Scheme 2B In general, the intermediate of formula (V) can be prepared according to the following reaction scheme 2B. In scheme 2B, W 1 represents fluoro, chloro, bromo, or iodine, BPin represents 4,4,5,5-tetramethyl-1,3,2-dioxaborolane, and all other variable elements are defined according to the scope of the present invention.

[0335] [ka]

[0336] In Scheme 2B, the following reaction conditions apply: Step 1: At a suitable temperature in the range of room temperature to 100°C, in the presence of a suitable base such as potassium carbonate, in the presence of a suitable catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2), in a suitable solvent such as dioxane or dimethylformamide and water; or R 2If =Me, boron-containing reagents such as trimethylboroxine can be used in the presence of a suitable catalyst such as (Pd(dppf)Cl2), in a suitable solvent such as dioxane or dimethylformamide and water, in the presence of an inorganic base such as potassium carbonate, at a reaction temperature of 80°C to 120°C; R 2 However, C 3~6 Cycloalkyl, C 1~4 C substituted with alkyl or 1, 2, or 3 halo substituents 1~4 Additional steps to achieve double bond reduction to obtain alkyl compounds: at a suitable temperature such as room temperature, in the presence of a suitable catalyst such as palladium carbon (Pd / C), in a suitable solvent such as methanol, under an H2 pressure such as 1-3 bar, and optionally in the presence of a base such as triethylamine; Step 2: At a suitable temperature such as 0°C to room temperature, in the presence of a suitable brominating reagent such as N-bromosuccinimide or CuBr2, in a suitable solvent such as dimethylformamide or acetonitrile; Step 3: For example, at a suitable temperature such as 80°C to 130°C, in the presence of a suitable catalyst such as copper (Cu), in the presence of a base such as potassium carbonate, and in a suitable solvent such as dimethylformamide; or, a copper(I) source such as CuI may be used at a temperature of 80°C to 150°C in the presence of a suitable diamine ligand such as trans-N,N'-dimethylcyclohexane-1,2-diamine, in the presence of an inorganic base such as potassium carbonate, and in an aprotic solvent such as dimethylformamide. In specific cases, the above conversion can also be carried out by nucleophilic aromatic substitution using an inorganic base such as potassium tert-butoxide or sodium hydride in an aprotic solvent such as dimethylformamide at a temperature of 0°C to 80°C. Those skilled in the art will understand that steps 2 and 3 of scheme 2B may be reversed; that is, intermediate (III) may be cross-coupled with reagent (Va) first, followed by bromination of the azaindole portion to obtain intermediate (V).

[0337] Scheme 3 In general, the intermediate of formula (VIIa) can be prepared via the intermediate of formula (VIe). The intermediate of formula (VIe) can also be prepared according to the following reaction scheme 3. In scheme 3, PG represents a suitable protecting group such as tert-butoxycarbonyl, and all other variable elements are defined according to the scope of the present invention.

[0338] [ka]

[0339] In Scheme 3, the following reaction conditions apply: Step 1: In a suitable temperature in the range of 70°C to 100°C, in the presence of a suitable base such as potassium phosphate, in the presence of a suitable catalyst such as palladium acetate (Pd(OAc)2), optionally in the presence of a suitable phosphine ligand such as 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (Davephos), in a suitable solvent such as dioxane or dimethylformamide; Step 2: At a suitable temperature such as room temperature, in the presence of a suitable heterogeneous catalyst such as palladium carbon (Pd / C), in a common solvent such as methanol, ethanol, or THF, under a hydrogen pressure such as 1 to 3 bar, and optionally in the presence of a base such as triethylamine;

[0340] Scheme 4 In general, the intermediate of formula (IXb) can be prepared according to the following reaction scheme 4. In scheme 4, PG represents a suitable protecting group such as tert-butoxycarbonyl, and all other variable elements are defined according to the scope of the present invention.

[0341] [ka] Step 1: In a suitable temperature such as -78°C, in the presence of a suitable deprotonating agent such as n-butyllithium, in the presence of a suitable reagent such as 2,2,6,6-tetramethylpiperidine (HTMP), and in a suitable solvent such as tetrahydrofuran;

[0342] Scheme 5 Generally, compounds of formula (Ia) can be prepared according to the following reaction scheme 5. In scheme 5, PG represents a suitable protecting group such as tert-butyloxycarbonyl, LG is a leaving group such as chloro, bromo, iodine, or tosylate, or mesylate, or triflate, and all other variable elements are defined according to the scope of the present invention.

[0343] [ka]

[0344] In Scheme 5, the following reaction conditions apply: Step 1: For example, at a suitable temperature such as 100°C, in the presence of a suitable catalyst such as copper (Cu), in the presence of a base such as potassium carbonate, and in a suitable solvent such as dimethylformamide; or, a copper(I) source such as CuI may be used at a temperature of 80°C to 150°C in the presence of a suitable diamine ligand such as trans-N,N'-dimethylcyclohexane-1,2-diamine, in the presence of an inorganic base such as potassium carbonate, and in an aprotic solvent such as dimethylformamide. Step 2: For example, at a suitable temperature such as room temperature, in the presence of a suitable coupling agent such as 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), in the presence of a base such as N,N-diisopropylethylamine (DIPEA), and in a suitable solvent such as dimethylformamide; or, the acid chloride can also be prepared by reacting intermediate VIII with thionyl chloride in an optional halogenated solvent such as dichloromethane at a temperature in the range of 0°C to room temperature. Then, optionally in an aprotic solvent such as dimethylformamide, and optionally in the presence of a tertiary amine such as N,N-diisopropylethylamine, the intermediate acid chloride is converted to amine HNR xa R xb You can have it react like that. Step 3: At a suitable temperature in the range of 60°C to 120°C, such as 100°C, in the presence of a suitable base such as potassium carbonate, in the presence of a suitable catalyst such as [1,1'-bis(diphenylphosphin)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2), in a suitable solvent such as dioxane or dimethylformamide and water; Step 4: At a suitable temperature such as room temperature, in the presence of a suitable heterogeneous catalyst such as palladium carbon (Pd / C), in a common solvent such as methanol, ethanol, or THF, under a hydrogen pressure such as 1 to 3 bar, and optionally in the presence of a base such as triethylamine; Step 5: In a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable acid, such as a protonic acid like trifluoroacetic acid (TFA) or hydrochloric acid, in a suitable solvent such as dichloromethane (DCM) or 1,4-dioxane; Step 6: For reductive amination reactions using aldehydes or ketones: at a suitable temperature in the range of room temperature to 70°C, in the presence of a suitable reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, in a suitable solvent such as methanol, dichloromethane, or 1,2-dichloroethane, and optionally in the presence of zinc chloride, sodium acetate, or acetic acid; LG-YR 3 For alkylation reactions using: for example, at a suitable temperature such as room temperature, in the presence of a suitable deprotonating agent such as sodium hydride or potassium carbonate, or an amine base such as triethylamine, in a suitable aprotic solvent such as dimethylformamide, dimethyl sulfoxide, or acetonitrile.

[0345] Scheme 6 In general, equation (Ib) [where R 1a -S(=O)2-R 18 ,

[0346] [ka] Limited to Q is -CHR yThe compound represented by - can be prepared according to the following reaction scheme 6. In scheme 6, PG represents a suitable protecting group such as tert-butyloxycarbonyl, 9-fluorenylmethoxycarbonyl, or benzyl, LG is a leaving group such as chloro, bromo, iodine, tosylate, or mesylate, LG1 is a leaving group such as fluoro, chloro, bromo, iodine, tosylate, or mesylate, and all other variable elements are defined according to the scope of the present invention.

[0347] [ka]

[0348] In Scheme 6, the following reaction conditions apply: Step 1: In a suitable temperature in the range of 50°C to 90°C, in the presence of a suitable base such as potassium hydroxide or sodium hydroxide, in a suitable solvent such as methanol, ethanol, or isopropanol, preferably a protic solvent. Step 2: At a suitable temperature such as room temperature, in the presence of a suitable heterogeneous catalyst such as palladium carbon (Pd / C), in a common solvent such as methanol, ethanol, or THF, under a hydrogen pressure such as 1 to 3 bar, and optionally in the presence of a base such as triethylamine; Step 3: At a suitable temperature in the range of 50°C to 100°C, in the presence of a suitable inorganic base such as potassium carbonate or potassium tert-butoxide, and in a suitable aprotic solvent such as dioxane, dimethylformamide, acetonitrile, or dimethyl sulfoxide; Step 4: In the case of PG=Boc, in a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable acid, such as a protic acid like trifluoroacetic acid or hydrochloric acid, and in a suitable solvent such as dichloromethane or 1,4-dioxane; Alternatively, if PG = 9-fluorenylmethoxycarbonyl, it is prepared at a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable base such as piperidine, and in a suitable solvent such as dichloromethane (DCM); Alternatively, if PG = benzyl, it can be measured at a suitable temperature such as room temperature, in the presence of a suitable heterogeneous catalyst such as palladium on charcoal (Pd / C), in a common solvent such as methanol, ethanol, or THF, under a hydrogen pressure such as 1-3 bar, and optionally in the presence of a base such as triethylamine; Step 5: For reductive amination reactions using aldehydes or ketones: at a suitable temperature in the range of room temperature to 70°C, in the presence of a suitable reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, in a suitable solvent such as methanol, dichloromethane, or 1,2-dichloroethane, and optionally in the presence of zinc chloride, sodium acetate, or acetic acid; LG-YR 3 For alkylation reactions using: for example, at a suitable temperature such as room temperature, in the presence of a suitable deprotonating agent such as sodium hydride or potassium carbonate, or an amine base such as triethylamine, in a suitable aprotic solvent such as dimethylformamide, dimethyl sulfoxide, or acetonitrile.

[0349] Scheme 7 Generally, compounds of formula (Ic) can be prepared according to the following reaction scheme 7. In scheme 7, PG represents a suitable protecting group such as tert-butyloxycarbonyl, 9-fluorenylmethoxycarbonyl, or benzyl, and all other variable elements are defined according to the scope of the present invention.

[0350] [ka]

[0351] In Scheme 7, the following reaction conditions apply: Step 1: In a suitable solvent such as tetrahydrofuran, at a suitable temperature such as -78°C, in the presence of a suitable deprotonating agent such as lithium bis(trimethylsilyl)amide (LiHMDS) and sodium hydride; Step 2: At a suitable temperature in the range of room temperature to 100°C, in the presence of a suitable catalyst such as rhodium acetate dimer (Rh2(OAc)4), in a suitable solvent such as dichloromethane; Step 3: At a suitable temperature in the range of room temperature to 100°C, in the presence of a suitable catalyst such as tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), in the presence of a suitable base such as morpholine, and in a suitable solvent such as tetrahydrofuran; Step 4: In a suitable temperature such as -78°C, in the presence of a suitable deprotonating agent such as n-butyllithium, in the presence of a suitable reagent such as 2,2,6,6-tetramethylpiperidine (HTMP), and in a suitable solvent such as tetrahydrofuran; Step 5: In a suitable solvent such as dioxane or dimethylformamide and water, in the presence of a suitable base such as potassium carbonate at a suitable temperature such as 100°C, and in the presence of a suitable catalyst such as [1,1'-bis(diphenylphosphin)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2); Step 6: At a suitable temperature such as room temperature, in the presence of a suitable heterogeneous catalyst such as palladium carbon (Pd / C), in a common solvent such as methanol, ethanol, or THF, under a hydrogen pressure such as 1 to 3 bar, and optionally in the presence of a base such as triethylamine; Step 7: In the case of PG=Boc, in a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable acid, such as a protic acid like trifluoroacetic acid or hydrochloric acid, in a suitable solvent such as dichloromethane or 1,4-dioxane; Alternatively, if PG = 9-fluorenylmethoxycarbonyl, it is prepared at a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable base such as piperidine, and in a suitable solvent such as dichloromethane (DCM); Alternatively, if PG = benzyl, it can be prepared at a suitable temperature such as room temperature, in the presence of a suitable heterogeneous catalyst such as palladium carbon (Pd / C), in a common solvent such as methanol, ethanol, or THF, under a hydrogen pressure such as 1-3 bar, and optionally in the presence of a base such as triethylamine; An example of steps 1 and 2 in Scheme 7 is the preparation of a five-membered intermediate (XVIIcc) as shown in Scheme 7a, which can be prepared according to the general procedure outlined in steps 1 and 2 of Scheme 7.

[0352] Scheme 7a

[0353] [ka]

[0354] Scheme 8 Generally, the intermediate of formula (XVIIId) can be prepared according to the following reaction scheme 8. In scheme 8, W2 represents chloro, bromo, or iodine, and all other variable elements are defined according to the scope of the present invention. Those skilled in the art will know that cyclobutyl in scheme 8 is generally C 3~6 It will be understood that the intermediate of formula (XVIIId) may be a cycloalkyl, and that the intermediate may be further functionalized to the compound of formula (I) by a reaction protocol similar to that described herein in combination with a standard synthetic process commonly used by those skilled in organic chemistry.

[0355] [ka]

[0356] In Scheme 8, the following reaction conditions apply: Step 1: In a suitable temperature such as 0°C, in the presence of a suitable condensation reagent such as propylphosphonic anhydride (T3P), in the presence of a base such as N,N-diisopropylethylamine (DIPEA), and in a suitable solvent such as dimethylformamide or dichloromethane; Step 2: In a suitable solvent such as tetrahydrofuran at a suitable temperature such as 0°C; Step 3: At a suitable temperature in the range of room temperature to 70°C, in the presence of a suitable reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, in a suitable solvent such as methanol, dichloromethane, or 1,2-dichloroethane, and optionally in the presence of zinc chloride, sodium acetate, or acetic acid; Step 4: In a suitable temperature in the range of 0°C to 40°C, such as room temperature, in the presence of a suitable acid such as hydrochloric acid (HCl, 1N), and in a suitable solvent such as acetonitrile.

[0357] Scheme 9 Generally, Q is -CHR y The intermediate represented by - in Scheme 9 can be prepared according to the following reaction scheme. In Scheme 9, PG represents a preferred protecting group such as tert-butyloxycarbonyl, and all other variable elements are defined according to the scope of the present invention.

[0358] [ka]

[0359] In Scheme 9, the following reaction conditions apply: Step 1: In a suitable solvent such as tetrahydrofuran, in the presence of zinc, in the presence of a suitable activator such as trimethylsilyl chloride or 1-bromo,2-chloroethane, at a suitable temperature in the range of room temperature to 70°C, for example, 60°C. Optionally, this procedure can also be carried out using a flow apparatus. Step 2: In a suitable solvent such as tetrahydrofuran, in the presence of a suitable catalyst such as a fourth-generation RuPhosPd pre-catalyst (RuPhosPd G4), at a suitable temperature in the range of room temperature to 70°C, for example, 50°C.

[0360] Scheme 10 Generally, Q is -CHR yThe intermediate represented by - in Scheme 10 can be prepared according to the following reaction scheme. In Scheme 10, PG represents a suitable protecting group such as tert-butyloxycarbonyl, and all other variable elements are defined according to the scope of the present invention. BPin represents 4,4,5,5-tetramethyl-1,3,2-dioxaborolane. 1 and W 3 This represents fluoro, chloro, bromo, or iodine.

[0361] [ka] Step 1: At a suitable temperature such as -78°C, in the presence of a suitable deprotonating agent such as n-butyllithium, in a suitable solvent such as tetrahydrofuran, and in the presence of a suitable electrophile such as DMF; Step 2: At a suitable temperature in the range of 80°C to 120°C, in the presence of a diol protecting reagent such as glycol, in the presence of a Brønsted acid such as p-toluenesulfonic acid, or in a suitable solvent such as toluene; Step 3: At a suitable temperature in the range of room temperature to 100°C, in the presence of a suitable base such as potassium carbonate, in the presence of a suitable catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)(Pd(dppf)Cl2), in a suitable solvent such as dioxane or dimethylformamide and water; or, if R2=Me, a boron-containing reagent such as trimethylboroxine can be used at a reaction temperature of 80°C to 120°C, in the presence of a suitable catalyst such as (Pd(dppf)Cl2), in a suitable solvent such as dioxane or dimethylformamide and water, in the presence of an inorganic base such as potassium carbonate; Step 4: In the presence of a suitable base such as sodium t-butoxide, a suitable palladium source such as palladium(II) acetate (Pd(OAc)2), a suitable ligand such as 1,1'-(9,9-dimethyl-9H-xanthene-4,5-diyl)bis[1,1-diphenylphosphine] or xanthophos, a suitable solvent such as 1,4-dioxane, and in a suitable temperature range of 50°C to 120°C; Step 5: In the presence of a suitable Brønsted acid such as hydrochloric acid, and a suitable solvent such as 1,4-dioxane or tetrahydrofuran and water, within a suitable temperature range such as room temperature to 60°C; Step 6: In a suitable solvent such as tetrahydrofuran, in the presence of a suitable deprotonating agent such as n-butyllithium, at a suitable temperature range such as -78°C to room temperature. Step 7: In the presence of a suitable Brønsted acid such as hydrochloric acid, and a suitable solvent such as 1,4-dioxane or tetrahydrofuran and water, within a suitable temperature range such as room temperature to 100°C; Step 8: In a suitable solvent such as dimethylformamide or acetonitrile, at a suitable temperature such as 0°C to room temperature, in the presence of a suitable brominating reagent such as N-bromosuccinimide or CuBr2; Step 9: For example, at a suitable temperature such as 80°C to 130°C, in the presence of a suitable catalyst such as copper (Cu), in the presence of a base such as potassium carbonate, and in a suitable solvent such as dimethylformamide. Alternatively, a copper(I) source such as CuI may be used at a temperature of 80°C to 150°C in the presence of a suitable diamine ligand such as trans-N,N'-dimethylcyclohexane-1,2-diamine, in the presence of an inorganic base such as potassium carbonate, and in an aprotic solvent such as dimethylformamide. In specific cases, the above conversion can also be carried out by nucleophilic aromatic substitution using an inorganic base such as potassium tert-butoxide or sodium hydride at a temperature of 0°C to 80°C in an aprotic solvent such as dimethylformamide. Step 10: In a suitable solvent such as dioxane or dimethylformamide and water, at a suitable temperature such as 100°C, in the presence of a suitable base such as potassium carbonate, and in the presence of a suitable catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2).

[0362] As can be understood by those skilled in the art, the intermediate obtained in Scheme 10 can be further refined to obtain the compound of formula (A) by using the procedures outlined in the general scheme above, particularly in Schemes 1 and 3.

[0363] Scheme 11 In general, the intermediates described in Scheme 11 can be prepared according to the following reaction scheme. In Scheme 11, PG represents a suitable protecting group, such as tert-butyloxycarbonyl, and all other variable elements are defined according to the scope of the present invention. BPin represents 4,4,5,5-tetramethyl-1,3,2-dioxaborolane.

[0364] [ka] Step 1: If PG'' is a silyl-containing protecting group, for example tert-butyldimethylsilyl, then in a suitable temperature range of room temperature to 80°C, such as room temperature, in the presence of a base such as imidazole, in the presence of a suitable reagent such as tert-butyldimethylsilyl chloride, and in a suitable solvent such as DMF. If PG'' is a different protecting group as defined herein, general protection conditions known to those skilled in the art can be used. Step 2: At a suitable temperature such as room temperature to 60°C, for example, in the presence of a suitable alkyl halide, for example, in the presence of a suitable base such as K2CO3, [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine-N 1 ,N 1’ In the presence of a suitable photocatalyst such as bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate, [Ir{dF(CF3)ppy}2(dtbpy)]PF6, a suitable nickel salt such as NiCl2-Glyme, a suitable ligand such as 4-4'-dimethoxy-2-2'-bipyridine, a suitable solvent such as acetonitrile, and water as an additive, blue LED irradiation was used (Johnston, C., Smith, R., Allmendinger, S. et al. Metallaphotoredox-catalyzed sp 3 -sp 3 cross-coupling of carboxylic acids with alkyl halides.Nature 536,322-325(2016)). Step 3: In a suitable solvent such as tetrahydrofuran, in the presence of a suitable fluoride source such as tetrabutylammonium fluoride, at a suitable temperature such as room temperature; if the PG is a different protecting group as defined herein, general protection conditions known to those skilled in the art may be used. Step 4: At a suitable temperature such as -78°C to 40°C, in the presence of Dess-Martin periodinane, in a suitable solvent such as dichloromethane. Other oxidation methods known to those skilled in the art may also be used. Step 5: In a suitable solvent such as tetrahydrofuran, at a suitable temperature such as -78°C, in the presence of a suitable deprotonating agent such as n-butyllithium, in the presence of a suitable reagent such as 2,2,6,6-tetramethylpiperidine (HTMP).

[0365] It will be understood that, given the presence of suitable functional groups, compounds of various formulas or any intermediates used in their preparation can be further derivatized by one or more standard synthetic methods employing condensation, substitution, oxidation, reduction, or cleavage reactions. Specific substitution techniques include conventional alkylation, arylation, heteroarylation, acylation, sulfonylation, halogenation, nitration, formylation, and coupling procedures.

[0366] The compound of formula (I) may be synthesized in the form of a racemic mixture of enantiomers, which can be separated from each other by decomposition procedures known in the art. A racemic compound of formula (I) containing a basic nitrogen atom may be converted to the corresponding diastereomer salt form by reaction with a suitable chiral acid. The diastereomer salt form is then separated, for example, by selective or fractional crystallization, and the enantiomer is liberated therefrom by alkali. An alternative method for separating the enantiomer forms of the compound of formula (I) includes liquid chromatography using a chiral stationary phase. The pure stereochemical isomer may also be derived from the corresponding pure stereochemical isomer of a suitable starting material, provided that the reaction occurs stereospecifically.

[0367] In the preparation of the compounds of the present invention, protection of the remote functional group (e.g., primary or secondary amine) of the intermediate may be necessary. The need for such protection will vary depending on the properties of the remote functional group and the conditions of the preparation method. Suitable amino protecting groups (NH-Pg) include acetyl, trifluoroacetyl, t-butoxycarbonyl (Boc), benzyloxycarbonyl (CBz), and 9-fluorenylmethyleneoxycarbonyl (Fmoc). The need for such protection will be readily determined by those skilled in the art. For a general description of protecting groups and their use, see TW Greene and PGMWuts, Protective Groups in Organic Synthesis, 4th ed., Wiley, Hoboken, New Jersey, 2007.

[0368] Pharmacology The compounds of the present invention have been found to inhibit the interaction between menin and MLL protein and oncogenic MLL fusion proteins themselves, or to be metabolized in vivo to a more active form (prodrug). Therefore, the compounds of the present invention and pharmaceutical compositions containing such compounds may be useful in the treatment or prevention, particularly in the treatment, of cancers including but not limited to leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN); as well as diseases such as diabetes.

[0369] In particular, the compounds and pharmaceutical compositions according to the present invention may be useful for the treatment or prevention of cancer. According to one embodiment, cancers that may benefit from treatment with the menin / MLL inhibitor of the present invention include leukemia, lymphoma, myeloma, or solid tumor cancers (e.g., prostate cancer, lung cancer, breast cancer, pancreatic cancer, colon cancer, liver cancer, melanoma, and glioblastoma). In some embodiments, leukemia includes acute leukemia, chronic leukemia, myeloid leukemia, myeloid leukemia, lymphoblastic leukemia, lymphocytic leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), T-cell prelymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, hairy cell leukemia (HCL), MLL rearrangement leukemia, MLL-PTD leukemia, MLL amplification leukemia, MLL-positive leukemia, and leukemia exhibiting a HOX / MEIS1 gene expression signature.

[0370] In particular, the compounds and pharmaceutical compositions according to the present invention may be useful for the treatment or prevention of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).

[0371] In particular, the compounds and pharmaceutical compositions according to the present invention may be useful for the treatment or prevention of leukemia, especially nucleophosmin (NPM1) variant leukemia, such as NPM1c.

[0372] In particular, the compounds and pharmaceutical compositions according to the present invention are effective against AML, especially nucleophosmin (NPM1) mutant AML (i.e., NPM1 mut It may be useful in the treatment or prevention of AML, more specifically in the treatment or prevention of NPM1 variant AML.

[0373] In particular, the compounds and pharmaceutical compositions according to the present invention may be useful for the treatment or prevention of MLL rearrangement leukemia, especially MLL rearrangement AML or ALL.

[0374] In particular, the compounds and pharmaceutical compositions according to the present invention may be useful for the treatment or prevention of leukemia with MLL gene modification, especially AML or ALL with MLL gene modification.

[0375] In particular, the compounds and pharmaceutical compositions according to the present invention may be suitable for QD administration (once a day).

[0376] In particular, the compounds and pharmaceutical compositions according to the present invention may be useful for the treatment or prevention of hematological malignancies in subjects exhibiting NPM1 gene mutations and / or mixed lineage leukemia gene (MLL;MLL1;KMT2A) modifications, mixed lineage leukemia (MLL), MLL-related leukemia, MLL-associated leukemia, MLL-positive leukemia, MLL-induced leukemia, rearranged mixed lineage leukemia, MLL-associated leukemia, MLL gene rearrangement / modification or rearrangement / modification, acute leukemia, chronic leukemia, myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), insulin resistance, prediabetes, diabetes, or risk of diabetes, hyperglycemia, chromosomal rearrangement on chromosome 11q23, type 1 diabetes, type 2 diabetes; promotion of pancreatic cell proliferation when pancreatic cells are islet cells, β-cells, and the proliferation of said β-cells is demonstrated by increased β-cell production or insulin production; and inhibition of menin-MLL interactions when the target gene of the MLL fusion protein is HOX or MEIS1 in humans.

[0377] Accordingly, the present invention relates to a compound of formula (I), its tautomers and stereoisomers, and pharmaceutically acceptable salts and solvates thereof, for use as a pharmaceutical.

[0378] The present invention also relates to the use of a compound of formula (I) according to the present invention, its tautomers or stereoisomers, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition for the manufacture of a pharmaceutical.

[0379] The present invention also relates to a compound of formula (I) according to the present invention, its tautomers or stereoisomers, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition, for use in the treatment, prevention, improvement, control, or reduction of the risk of disorders associated with the interaction between menin and MLL proteins and oncogenic MLL fusion proteins in mammals, including humans, wherein such treatment or prevention is affected or promoted by inhibiting the interaction between menin and MLL proteins and oncogenic MLL fusion proteins.

[0380] Furthermore, the present invention relates to the use of a compound of formula (I) according to the present invention, its tautomer or stereoisomer, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition for producing a pharmacopoeia for treating, preventing, improving, controlling, or reducing the risk of disorders related to the interaction between menin and MLL proteins and oncogenic MLL fusion proteins in mammals, including humans, wherein such treatment or prevention is affected or promoted by inhibiting the interaction between menin and MLL proteins and oncogenic MLL fusion proteins.

[0381] The present invention also relates to a compound of formula (I), its tautomers or stereoisomers, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment or prevention of any one of the aforementioned diseases.

[0382] The present invention also relates to a compound of formula (I), its tautomers or stereoisomers, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment or prevention of any one of the aforementioned diseases.

[0383] The present invention also relates to the use of a compound of formula (I), its tautomer or stereois...

Claims

1. Equation (I) 【Chemistry 101】 [In the formula, Q is -CHR ｙ - or -CR ｙ The dotted line represents the equals sign, and Q is -CR. ｙ An optional additional bond to form a double bond when representing equality. R １ａ is hydrogen, halo, -C(=O)-NR ｘａ R ｘｂ , -S(=O) ２ -R １８ , -C(=O)-O-C １～４ alkyl, or 【Chemical Engineering 102】 This represents, R １８ However, C １～６ Represents alkyl, R １９ However, hydrogen or C １～６ Represents alkyl, or R １８ and R １９ Together, - (CH ２ ) ３ -, - (CH ２ ) ４ - or - (CH ２ ) ５ - forms, R ｘａ and R ｘｂ However, each independently, hydrogen, Het ３ , C ３～６ Cycloalkyl, and C １～６ Alkyl (at this time, optionally, the C ３～６ Cycloalkyl and the C １～６ The alkyl groups are independently -OH and -OC. １～４ Alkyl and -C １～４ (Substituted with one, two, or three substituents selected from the group consisting of alkyl-OH, or R ｘａ and R ｘｂ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, together with the N atom to which they are bonded (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally forms C １～４ Alkyl, -OH, -O-C １～４ Alkyl, and 1, 2, or 3 OR ２３ C replaced by １～４ It is substituted with one, two, or three substituents selected from the group consisting of alkyl groups, or R ｘａ and R ｘｂ These combine to form a 6- to 11-membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl is optionally substituted with 1, 2, or 3 -OH substituents, R ２３ However, hydrogen or C １～４ Represents alkyl, R １ｂ However, F or -O-C １～４ Represents alkyl, R ２ But, hello, C １～４ C substituted with alkyl or 1, 2, or 3 halo substituents １～４ Represents alkyl, R ２１ However, hydrogen or -Y ａ -R ３ａ This represents, however, R ２１ ga-Y ａ -R ３ａ When representing -Y ａ -R ３ａ and -Y-R ３ Provided that one of them is bonded to the nitrogen atom of the ring, Y and Y ａ However, each is independent, covalently bonded or 【Transformation 3】 This represents, R5 represents hydrogen, n1 is selected from 1 and 2. n2 is selected from 1, 2, and 3. R ｙ However, it represents hydrogen, R ３ , R ３ａ , and R ４ However, each operates independently, Het １ ; C １～８ Alkyl; and each independently -C(=O)-Het ６ａ , -C(=O)-Het ６ｂ , -NR １０ｃ -C (=O) -C １～４ Alkyl, -NR ｘｃ R ｘｄ , -NR ８ａ R ８ｂ , -CF ３ , halo, -OH, -O-C １～４ Alkyl, Het １ , Het ２ Ar １ , and Cy ２ C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of １～８ Selected from the group consisting of alkyl groups, R ｘｃ and R ｘｄ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, together with the N atom to which they are bonded (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -(C=O)-C １～４ Alkyl and -S (=O) ２ -C １～４ It is substituted with one, two, or three substituents selected from the group consisting of alkyl groups, or R ｘｃ and R ｘｄ together with the N atom to which they are attached form a 6- to 11-membered bicyclic fully or partially saturated heterocyclyl containing one N atom and optionally one or two additional heteroatoms each independently selected from O, S, and N, where the S atom may be substituted to form S(=O) or S(=O) ２ ), and the heterocyclyl is optionally substituted with one, two, or three substituents selected from the group consisting of -(C=O)-C １～４ alkyl and -S(=O) ２ -C １～４ alkyl R ８ａ and R ８ｂ However, each independently, hydrogen; C １～６ Alkyl; -(C=O)-C １～４ Alkyl; and C substituted with 1, 2, or 3 -O-C1-4 alkyl groups. １～６ Selected from the group consisting of alkyl groups, Ar １ is optionally, each independently, C １～４ alkyl and -C(=O)-NR １０ａ R １０ｂ represents phenyl substituted with 1, 2, or 3 substituents selected from the group consisting of Het １ However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom is substituted to S(=O) or S(=O) ２ (may form a bicyclic C bond containing 1, 2, or 3 heteroatoms independently selected from O, S, and N) or a 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted with S(=O) or S(=O) ２ (may form) and the heterocyclil optionally has R on one nitrogen. ６ , -C(=O)-Cy １ , and -C(=O)-R ８ The heterocyclyl is substituted with substituents selected from the group consisting of, and optionally, one or two carbon atoms each independently have a halo, R ６ , C １～４ Substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl, oxo, and -OH, Het ２ However, it represents C-linked pyrazolyl, 1,2,4-oxadiazolyl, pyridazinyl, or triazolyl. R6, Het ３ ;Het ４ ;-C(=O)-NH-Cy １ ;-C(=O)-NH-R ８ ;-C(=O)-Het ６ａ ;-C(=O)-NR １０ｄ R １０ｅ ;-C(=O)-OC １～４ Alkyl; -S (=O) ２ -C １～４ Alkyl; optional, each independently of Het ６ａ , Het ６ｂ C substituted with one or two substituents selected from the group consisting of and -OH １～６ Selected from the group consisting of alkyl groups, R ８ However, hydrogen, -O-C １～６ Alkyl, C １～６ Alkyl, or each independently -OH, -O-C １～４ Alkyl, cyano, -S (=O) ２ -C １～４ C substituted with one, two, or three substituents selected from alkyl and Het3a １～６ Represents alkyl, Het ３ And Het3a each independently contains one, two, or three heteroatoms selected from O, S, and N, forming a monocyclic 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -(C=O)-C on one nitrogen atom. １～４ Substituted with alkyl, Het4 represents a monocyclic carbon bonded 5 or 6-membered aromatic ring, each independently containing 1, 2, or 3 heteroatoms selected from O, S, and N, wherein the aromatic ring optionally has 1 or 2 carbon atoms, each independently containing C １～４ Alkyl and -C(=O)-NR １０ａ R １０ｂ Substituted with a total of one or two substituents selected from the group consisting of, Het6a is a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has a halo and -S (=O) on one or two carbon atoms, each independently. ２ -C １～４ The heterocyclyl is substituted with a total of 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups, and the heterocyclyl optionally has -C(=O)-C substituents on one nitrogen atom. １～４ Alkyl and -S (=O) ２ -C １～４ Substituting with substituents selected from the group consisting of alkyl groups, Het6b is a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-C on one nitrogen. １～４ Substituted with alkyl, Cy １ However, C can be optionally substituted with 1, 2, or 3 -OH groups. ３～６ Represents cycloalkyl, Cy ２ However, C ３～７ Cycloalkyl or 5-12 member saturated carbon bicyclic system (in this case, the C ３～７ The cycloalkyl or the carbon bicyclic system can be optionally selected, and each can be independently a halo, R ６ , -C(=O)-Het ６ａ , Het ６ａ , Het ６ｂ , -NR ９ａ R ９ｂ , -OH, and C １～４ (represented by being substituted with 1, 2, 3, or 4 substituents selected from alkyl groups) R ９ａ and R ９ｂ However, each independently, hydrogen; C １～４ Alkyl; -C(=O)-C １～４ Alkyl; -S (=O) ２ -C １～４ Selected from the group consisting of alkyl and -C(=O)-R14, R １０ａ , R １０ｂ , and R １０ｃ However, each independently, hydrogen and C １～４ Selected from the group consisting of alkyl groups, R １０ｄ and R １０ｅ However, each is independent, C １～４ Alkyl and -O-C １～４ Selected from the group consisting of alkyl groups, R １４ However, -O-C １～４ [Represents alkyl] Compounds thereof, or their tautomers or stereoisomers, or pharmaceutically acceptable salts thereof, or solvates thereof.

2. Q is -CHR ｙ - or -CR ｙ The dotted line represents the equals sign, and Q is -CR. ｙ An optional additional bond to form a double bond when representing equality. R １ａ However, hydrogen, halo, -C(=O)-NR ｘａ R ｘｂ , or 【Chemistry 105】 This represents, R ｘａ and R ｘｂ However, each is independent of hydrogen, Het3, and C. １～６ Alkyl (at this time, optionally, the C １～６ The alkyl groups are independently -OH and -OC １～４ (Substituted with one, two, or three substituents selected from the group consisting of alkyl groups) or R ｘａ and R ｘｂ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, together with the N atom to which they are bonded (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally forms C １～４ Alkyl, -OH, and -O-C １～４ It is substituted with one, two, or three substituents selected from the group consisting of alkyl groups, or R ｘａ and R ｘｂ These combine to form a 6- to 11-membered bicyclic complete or partially saturated heterocycline containing one N atom and, optionally, one or two additional heteroatoms independently selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally forms C １～４ Alkyl, -OH, and -O-C １～４ Substituted with one, two, or three substituents selected from the group consisting of alkyl groups, R １ｂ However, it represents F, R ２ But, hello, C １～４ C substituted with alkyl or 1, 2, or 3 halo substituents １～４ Represents alkyl, R ２１ However, it represents hydrogen, R ｙ However, it represents hydrogen, R ５ However, it represents hydrogen, R3 and R ４ However, each operates independently, Het １ ;Cy ２ ; C １～６ alkyl; and each independently -NR ｘｃ R ｘｄ , -NR ８ａ R ８ｂ , -CF ３ ,-OH,Het １ , and Cy ２ C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of １～６ Selected from the group consisting of alkyl groups, R ｘｃ and R ｘｄ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, together with the N atom to which they are bonded (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -(C=O)-C １～４ Alkyl and -S (=O) ２ -C １～４ It is substituted with one, two, or three substituents selected from the group consisting of alkyl groups, or R ｘｃ and R ｘｄ These combine to form a 6- to 11-membered bicyclic complete or partially saturated heterocycline containing, together with the N atom to which they are bonded, one N atom and one or two additional heteroatoms optionally and independently selected from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -(C=O)-C １～４ Alkyl and S (=O) ２ -C １～４ Substituted with one, two, or three substituents selected from the group consisting of alkyl groups, R ８ａ and R ８ｂ However, each is independent, C １～６ Alkyl; and C substituted with one -O-C1-4 alkyl group. １～６ Selected from the group consisting of alkyl groups, Het １ However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom is substituted to S(=O) or S(=O) ２ (may form a bicyclic C bond containing 1, 2, or 3 heteroatoms independently selected from O, S, and N) or a 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has R6 and -C(=O)-R on one nitrogen. ８ The heterocyclyl is substituted with substituents selected from the group consisting of the following, and the heterocyclyl is optionally oxo and -NR on one or two carbon atoms, each independently. ９ａ Substituted with a total of one or two substituents selected from the group consisting of R9b, R 6, Het ４ ;-C(=O)-NH-R ８ ; -S (=O) ２ -C １～４ Alkyl; or C １～６ Represents alkyl, R ８ However, -O-C １～６ Alkyl, C １～６ Alkyl, or each independently -O-C １～４ C substituted with one, two, or three substituents selected from alkyl and cyano groups. １～６ Represents alkyl, Het3 represents a monocyclic 4-7 member complete or partially saturated heterocycline containing one, two, or three heteroatoms independently selected from O, S, and N. Het4 represents a monocyclic 5- or 6-membered aromatic ring with carbon bonds containing one, two, or three heteroatoms independently selected from O, S, and N, or a fused bicyclic 9- or 10-membered aromatic ring with carbon bonds containing one, two, three, or four heteroatoms independently selected from O, S, and N (in which case the aromatic ring is optionally substituted on one or two carbon atoms with a total of one or two -C(=O)-NR 10a R 10b). Het6a is a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ The heterocyclyl may be substituted with a total of one or two -S(=O)2-C1-4 alkyl groups on one or two carbon atoms, and the heterocyclyl may be substituted with a total of one or two -C(=O)-C1-4 alkyl groups on one nitrogen atom. １～４ Alkyl and -S (=O) ２ -C １～４ Substituting with substituents selected from the group consisting of alkyl groups, Het6b is a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline, each independently containing one N atom and one or two additional heteroatoms optionally selected independently from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-C on one nitrogen. １～４ Substituted with alkyl, Cy ２ However, C ３～７ Cycloalkyl or 5-12 member saturated carbon bicyclic system (in this case, the C ３～７ The cycloalkyl or the carbon bicyclic system is optionally selected, and each is independently R ６ , -C(=O)-Het ６ａ , Het ６ａ , Het ６ｂ , -NR ９ａ R ９ｂ , 【Transformation 7】 (represented by being substituted with 1, 2, 3, or 4 substituents selected from the group consisting of) R ９ａ and R ９ｂ However, each independently, hydrogen; C １～４ Alkyl; -C(=O)-C １～４ Alkyl; and -S (=O) ２ -C １～４ Selected from the group consisting of alkyl groups, R ２０ａ and R ２０ｂ However, each independently, hydrogen and C １～４ A compound according to claim 1, selected from the group consisting of alkyl groups.

3. Q is -CHR ｙ - or -CR ｙ The dotted line represents the equals sign, and Q is -CR. ｙ An optional additional bond to form a double bond when representing equality. R １ａ However, hydrogen, halo, or -C(=O)-NR ｘａ Represents Rxb, R ｘａ and R ｘｂ However, each independently, hydrogen and C １～６ Selected from the group consisting of alkyl groups, R １ｂ However, it represents F, R ２ But, hello, C １～４ C substituted with alkyl or 1, 2, or 3 halo substituents １～４ Represents alkyl, R ２１ However, it represents hydrogen, R y represents hydrogen, R ５ However, it represents hydrogen, R 3 and R ４ However, each operates independently, Het １ ;Cy 2;C1-6 alkyl; and each independently -NR ｘｃ R ｘｄ , -NR ８ａ R ８ｂ , Het １ , and Cy ２ Selected from the group consisting of C1-6 alkyl groups substituted with 1, 2, 3, or 4 substituents, R ｘｃ and R ｘｄ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -(C=O)-C １～４ Alkyl and -S (=O) ２ -C １～４ It is substituted with one, two, or three substituents selected from the group consisting of alkyl groups, or R ｘｃ and R ｘｄ These combine to form a 6- to 11-membered bicyclic complete or partially saturated heterocycline containing, together with the N atom to which they are bonded, one N atom and one or two additional heteroatoms optionally and independently selected from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -(C=O)-C １～４ Alkyl and -S (=O) ２ -C １～４ Substituted with one, two, or three substituents selected from the group consisting of alkyl groups, R ８ａ and R ８ｂ However, each is independent, C １～６ Alkyl; and one -O-C １～４ C substituted with alkyl １～６ Selected from the group consisting of alkyl groups, Het １ However, each represents a monocyclic 4-7 member complete or partially saturated heterocycline containing one, two, or three heteroatoms independently selected from O, S, and N, wherein the heterocycline optionally has R6 and -C(=O)-R on one nitrogen atom. ８ Substituted with a substituent selected from the group consisting of, R ６ However, Het ４ ;-C(=O)-NH-R ８ ; or -S (=O) ２ -C １～４ Represents alkyl, R ８ However, -O-C １～６ Alkyl, C １～６ Alkyl; or each independently -O-C １～４ C substituted with one, two, or three substituents selected from alkyl and cyano １～６ Represents alkyl, Het ４ However, each independently contains one, two, or three heteroatoms selected from O, S, and N, representing a monocyclic 5 or 6-membered aromatic ring with carbon bonds, or each independently contains one, two, three, or four heteroatoms selected from O, S, and N, and the aromatic ring is optionally substituted on one or two carbon atoms with a total of one or two -(C=O)-NR 10a R 10b groups. Het ６ａ However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected by choice from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ The heterocyclyl may be substituted with a total of one or two -S(=O)2-C1-4 alkyl groups on one or two carbon atoms, and the heterocyclyl may be substituted with a total of one or two -C(=O)-C1-4 alkyl groups on one nitrogen atom. １～４ Alkyl and -S (=O) ２ -C １～４ Substituting with substituents selected from the group consisting of alkyl groups, Het ６ｂ However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected by choice from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-C on one nitrogen. １～４ Substituted with alkyl, Cy ２ However, each can be chosen independently and R ６ , Het ６ａ , Het ６ｂ , and -NR ９ａ Represents a C3-7 cycloalkyl group substituted with one, two, three, or four substituents selected from the group consisting of R9b. R ９ａ and R ９ｂ However, each independently, hydrogen, C １～４ Alkyl, -C(=O)-C １～４ Alkyl and -S (=O) ２ -C １～４ Selected from the group consisting of alkyl groups, R １０ａ And R10b, independently, contain hydrogen and C １～４ A compound according to claim 2, selected from the group consisting of alkyl groups.

4. Q is -CHR ｙ - represents, R １ａ However, -C(=O)-NR ｘａ Represents Rxb, R ｘａ and R ｘｂ However, C １～６ Represents alkyl, R １ｂ However, it represents F, R ２ However, Halo or C １～４ Represents alkyl, R ２１ However, it represents hydrogen, R ｙ However, it represents hydrogen, R ５ However, it represents hydrogen, R3, Het １ ;Cy ２ ; C １～６ alkyl; and each independently -NR ｘｃ R ｘｄ , Het １ , and Cy ２ C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of １～６ Selected from the group consisting of alkyl groups, R4 represents C1-6 alkyl, R ｘｃ and R ｘｄ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl is optionally substituted with 1, 2, or 3 -(C=O)-C1-4 alkyl groups, Het １ However, each represents a monocyclic 4-7 member complete or partially saturated heterocycline containing 1, 2, or 3 heteroatoms independently selected from O, S, and N, wherein the heterocycline optionally has R on one nitrogen atom. ６ and -C(=O)-R ８ Substituted with a substituent selected from the group consisting of, R ６ However, Het ４ Or it represents -C(=O)-NH-R8, R ８ However, C １～６ Alkyl, or each independently -O-C １～４ C substituted with one, two, or three substituents selected from alkyl and cyano １～６ Represents alkyl, Het ４ However, each contains one, two, or three heteroatoms independently selected from O, S, and N, forming a monocyclic 5- or 6-membered aromatic ring with carbon bonds, or each contains one, two, three, or four heteroatoms independently selected from O, S, and N, forming a condensed bicyclic 9- or 10-membered aromatic ring with carbon bonds (in this case, the aromatic ring may optionally contain a total of one or two -(C=O)-NR atoms on one or two carbon atoms). １０ａ R １０ｂ (represented by being replaced by) Het ６ａ However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected by choice from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-C on one nitrogen. １～４ Substituted with alkyl, Het ６ｂ However, a bicyclic N-bonded 6- to 11-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected by choice from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-C at one nitrogen. １～４ Substituted with alkyl, Cy ２ However, each can be chosen independently and R ６ , Het ６ａ , Het ６ｂ , and -NR ９ａ Represents a C3-7 cycloalkyl group substituted with one, two, three, or four substituents selected from the group consisting of R9b. R ９ａ and R ９ｂ However, each independently, hydrogen and -S (=O) ２ -C １～４ Selected from the group consisting of alkyl groups, The compound according to claim 3, wherein R 10a and R 10b are each independently selected from the group consisting of hydrogen and C1-4 alkyl groups.

5. Q is -CHR ｙ - represents, R １ａ However, -C(=O)-NR ｘａ R ｘｂ This represents, R ｘａ and R ｘｂ However, C １～６ Represents alkyl, R １ｂ However, it represents F, R ２ However, C １～４ Represents alkyl, R ２１ However, it represents hydrogen, R ｙ However, it represents hydrogen, R ５ However, it represents hydrogen, R3 is Cy ２ ; and each independently -NR ｘｃ R ｘｄ , Het １ , and Cy ２ C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of １～６ Selected from the group consisting of alkyl groups, R4 represents C1-6 alkyl, R ｘｃ and R ｘｄ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, wherein the heterocycline is optionally substituted with 1, 2, or 3 -(C=O)-C1-4 alkyl groups. Het １ However, each independently represents a monocyclic 4-7 member complete or partially saturated heterocycline containing 1, 2, or 3 heteroatoms selected from O, S, and N, wherein the heterocycline is optionally substituted with -C(=O)-R8 at one nitrogen atom. R ６ However, this represents -C(=O)-NH-R8, R ８ However, C １～６ Represents alkyl, Het ６ａ However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected by choice from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-C on one nitrogen. １～４ Substituted with alkyl, Cy ２ However, each can be selected independently and R ６ C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of and Het6a ３～７ Representing cycloalkyl, The compound according to claim 4.

6. Q is -CHR ｙ - represents, R １ａ However, -C(=O)-NR ｘａ R ｘｂ This represents, R ｘａ and R ｘｂ However, C can be optionally substituted with 1, 2, or 3 -OH groups. １～６ It is alkyl, R １ｂ However, it represents F, R ２ However, it represents methyl, R ２１ However, it represents hydrogen or methyl, Y represents a covalent bond, n1 is 1, n2 is selected from 1 and 2. R ｙ However, it represents hydrogen, R ３ However, each is independent -NR ｘｃ R ｘｄ , Het １ , and Cy ２ C substituted with 1, 2, 3, or 4 substituents selected from the group consisting of １～８ Selected from alkyl groups, R ｘｃ and R ｘｄ These combine to form a 4- to 7-membered monocyclic complete or partially saturated heterocycline containing one N atom and one additional heteroatom optionally selected from O, S, and N, together with the N atom to which they are bonded (in this case, the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has 1, 2, or 3 -(C=O)-C １～４ Substituted with alkyl, Het １ However, each contains one, two, or three heteroatoms independently selected from O, S, and N, in a monocyclic C-bonded 4- to 7-membered complete or partially saturated heterocycline (in which case the S atom is substituted to S(=O) or S(=O) ２ (may form a bicyclic C bond containing 1, 2, or 3 heteroatoms independently selected from O, S, and N) or a 6-11 member complete or partially saturated heterocycline (in which case the S atom may be substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-R on one nitrogen. ８ The heterocyclyl is substituted with an oxo on one carbon atom, R ８ However, C １～６ Alkyl, or each independently -OH, -O-C １～４ C substituted with one, two, or three substituents selected from alkyl and cyano groups. １～６ Represents alkyl, Het ６ａ However, a monocyclic N-bonded 4- to 7-membered complete or partially saturated heterocycline containing one N atom and one or two additional heteroatoms, each independently selected by choice from O, S, and N (in which case the S atom is substituted with S(=O) or S(=O) ２ (may form) and the heterocyclyl optionally has -C(=O)-C on one nitrogen. １～４ Substituted with alkyl, Cy ２ However, you can choose one Het ６ａ C replaced by ３～７ The compound according to claim 1, which represents a cycloalkyl group.

7. R ２１ The compound according to claim 1, wherein represents hydrogen.

8. R ２ The compound according to any one of claims 1 to 7, wherein represents methyl.

9. R １ｂ A compound according to any one of claims 1 to 8, wherein F represents the compound.

10. The compound according to any one of claims 1 to 9, wherein formula (I) is limited to formula (I-x). 【Chemistry 12】

11. The compound is 【Chemical 110】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

12. The compound is 【Chemistry 111】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

13. The compound according to claim 12, wherein the compound is an HCOOH salt.

14. The compound is 【Chemistry 112】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

15. The compound according to claim 14, wherein the compound is an HCOOH salt.

16. The compound is 【Chemistry 113】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

17. The compound is 【Chemistry 114】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

18. The compound is 【Chemical 115】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

19. The compound according to claim 18, wherein the compound is a monoHCl trihydrate salt.

20. A pharmaceutical composition comprising the compound described in any one of claims 1 to 19.

21. A pharmaceutical composition according to claim 20, for use as a pharmaceutical.

22. A pharmaceutical composition according to claim 20 for use in the prevention or treatment of cancer.

23. The pharmaceutical composition according to claim 20, for use in the prevention or treatment of leukemia, myelodysplastic syndrome (MDS), or myeloproliferative neoplasm (MPN).

24. A pharmaceutical composition for use in the prevention or treatment of leukemia as described in claim 23, wherein the leukemia is (NPM1) variant leukemia.

25. A pharmaceutical composition for use in the prevention or treatment of leukemia according to claim 23, wherein the leukemia is selected from acute leukemia, chronic leukemia, myeloid leukemia, myeloid leukemia, lymphoblastic leukemia, lymphocytic leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), T-cell prelymphoblastic leukemia (T-PLL), large granular lymphocytic leukemia, hairy cell leukemia (HCL), KMT2A-rearrangement leukemia, KMT2A-PTD leukemia, KMT2A-amplified leukemia, KMT2A-positive leukemia, and leukemia exhibiting a HOX / MEIS1 gene expression signature.

26. The pharmaceutical composition according to claim 25 for use in the treatment of AML.

27. ​​The pharmaceutical composition according to claim 26, wherein the AML is (NPM1) mutant AML.

28. The pharmaceutical composition according to claim 25 for use in the treatment of KMT2A gene rearrangement AML or ALL.

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