Compounds with novel substituted glutarimidyl-isoindolinone skeleton, and uses thereof

Abstract

The present invention relates to a compound of formula (I), a compound of formula (I'), or a salt, an enantiomer, a stereoisomer, a solvate or a polymorph thereof, and the use thereof. The present invention further relates to a pharmaceutical composition containing the compound of formula (I), the compound of formula (I'), or the salt, the enantiomer, the stereoisomer, the solvate or the polymorph thereof as an active ingredient, and the use thereof. The designed and synthesized compound can effectively prevent or treat diseases or disorders associated with the cereblon protein.

Description

[0065] In some embodiments of the present disclosure, Ry1 represents -S-, -S-CH2-, or -S-CH2- CH2-.

[0066] In some embodiments of the present disclosure, the compound of Formula (I) is also represented by Formula (I-4): 0 O (Ras)m (Rd2)n2 (Rd3)n3 (I-4) wherein Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, R, ring B, (Rd2)n2, m1, ring C, and (Rd3)n3 are as defined in the compounds of Formula (I) above and the various embodiments thereof.

[0067] In some embodiments of the present disclosure, the compound of Formula (I) is also represented by Formula (I-5): wherein Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, R, ring B, (Rd2)n2, m1, ring C, and (Rd3)n3 are as defined in the compounds of Formula (I) above and the various embodiments thereof; Rc1 represents H, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), or optionally substituted linear or branched C1-10 alkyl (e.g., optionally substituted linear or branched C1-6 alkyl or optionally substituted linear or branched C1-3 alkyl); and Rc2 represents optionally substituted C3-30 cycloalkyl (e.g., optionally substituted C3-20 cycloalkyl or optionally substituted C3-15 cycloalkyl), optionally substituted C5-30 aryl (e.g., optionally substituted C5-20 aryl or optionally substituted C5-15 aryl), optionally substituted 4- to 30-membered heterocyclyl (e.g., optionally substituted 4- to 20membered heterocyclyl or optionally substituted 4- to 15-membered heterocyclyl), or optionally substituted 5- to 30-membered heteroaryl (e.g., optionally substituted 5- to 20-membered heteroaryl or optionally substituted 5- to 15-membered heteroaryl).

[0068] In some embodiments of the compounds of Formula (I-5) of the present disclosure, Rc1 represents optionally substituted linear or branched C1-10 alkyl. Examples of linear or branched C1-10 alkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, and octyl. In some embodiments, linear or branched C1-10 alkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 16, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, mercapto, cyano, nitro, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl.

[0069] In some embodiments of the compounds of Formula (I-5) of the present disclosure, Rc2 represents optionally substituted C3-30 cycloalkyl (e.g., optionally substituted C3-20 cycloalkyl or optionally substituted C3-15 cycloalkyl), optionally substituted C5-30 aryl (e.g., optionally substituted C5-20 aryl or optionally substituted C5-15 aryl), optionally substituted 4- to 30-membered heterocyclyl (e.g., optionally substituted 4- to 20-membered heterocyclyl or optionally substituted 4- to 15-membered heterocyclyl) or optionally substituted 5- to 30-membered heteroaryl (e.g., optionally substituted 5- to 20-membered heteroaryl or optionally substituted 5- to 15-membered heteroaryl). In some embodiments, examples of C3-30 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spiro-cycloalkyl (e.g., C5-C15 spiro-cycloalkyl, C5-C20 spiro-cycloalkyl, or C5-C25 spiro-cycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, and spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C15 bridged cycloalkyl, C6-C20 bridged cycloalkyl, or C6-C25 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl). In some embodiments, C3-30 cycloalkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl. In some embodiments, examples of 4- to 30-membered heterocyclyl include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, pyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxy-piperidinyl, difluoro-piperidinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, dioxacyclohexyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl     (e.g.,     1,4-diazacycloheptanyl,     4,5-diazacycloheptanyl,     1,3- diazacycloheptanyl), diazacyclooctyl, bridged heterocyclyl (e.g., 6- to 20-membered bridged heterocyclyl, such as 6-azabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl,      2,5-diazabicyclo[2.2.2]octanyl,       and      quinuclidinyl), azaspirocycloalkyl (e.g.,   5- to 20-membered azaspirocycloalkyl, such as 2,6- diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl, and 7-azaspiro[3.5]nonanyl), and octahydropyrrolo[3,4-c]pyrrolyl. In some embodiments, 4- to 30-membered heterocyclyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, amino, cyano, oxo, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl. In some embodiments, examples of C5-30 aryl include, but are not limited to, phenyl and naphthyl. In some embodiments, C5-30 aryl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl. In some embodiments, examples of 5- to 30-membered heteroaryl include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl,        benzisothiazolyl,        benzotriazolyl,        benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7- tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl. In some embodiments, 5- to 30-membered heteroaryl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl.

[0070] In some embodiments of the present disclosure, the compound of Formula (I) is also represented by Formula (II-1), Formula (II-2), Formula (II-3), or Formula (II-4): wherein Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, R, Rc, ring B, (Rd2)n2, ring C, (Rd3)n3, and m1 are as defined in the compounds of Formula (I) above and the various embodiments thereof.

[0071] Preferably the compounds of the present invention and their salts (especially pharmaceutically acceptable salts, such as hydrochloride, etc.), enantiomers, diastereomers, solvates, or polymorphs thereof in Table 1 below are provided: Table 1. The compounds of the present invention Compoun d No. Structure of the compounds Compoun d No. Structure of the compounds GT-06422 Z—' y) 0 GT-06866 0 z CD GT-10308 0 0        F-X F u GT-06867 qYf'Y Xn^Y^f 0=( )— N                1 1 J 1 1 hn—f oo         o GT-06401 6-, GT-06868 h        YYF / ~v / ~rYrN'N^ r / X xJJ 0 0 GT-06541 0 0                 1 Y F GT- 06869 h       Xl oxyxxXO (5101 YnX yXY Y-N-.N-Y 0 00 GT-06542 Yl^OYY 0 o                1 T Cl GT-06870 —z c X 0 GT-06543 °\ GT-06871 >0 0 u X 0 GT-10084 o       H YXXXO-XJ 0 0                  1 0 GT-06911 0 rfv^ »xXX 6 0 0 0              |-| YXyG" O-Xl 0 0               1 u GT-06902 0 rYN^-"Q 0 0                       Cl GT-10494 o 0                    1 o GT-07209 0 0 0                       i. GT-10509 o       H X'X'XO 00       X X N u GT-06903 0 ry^-'T 0 0                                 [!: GT-10166 0       H ^yCTOXJ 00 $ Cl GT-07211 0 px-0 OO GT-06441 o       H 0 0              0 V Cl GT-06904 o   ryN^C °X-X> y 00               Cl GT-06544 0       H oM Vn       I i J,        I 0 o                                  [I ■-''"Ml GT-07212 o °x"Mn^2O"     Cj 00              Cl GT-06545 O    H        fY M / MJ k N XJ GT-06905 0 °x"MvCX    Cj hm^ 00              Cl GT-06436 2     h          Ml oxm^^QX^ HNM      'MMM 0 0 GT-07214 o °x"M\MX    CJ hm^ 00              Cl GT-10207 ° h      M °XNXrN'N^-^^ 0 0 GT-07057 o .^YY ■’o hm^               y^ 00              Cl GT-10297 o       H °mXnmT O JM 0 0 GT-06906 Q mVy^ / \ J J H J GT-06469 X'M °° $ Cl GT-06907 Cl xo 0 GT-06473 9,          H <A_ MM °X Jn X । l 1 L HnJ JrXz XNXX °° $ F GT-06908 0 0 GT-06509 o       H XJ'MMjJ °”     2$ F GT-06909 Cl , . ' AA 2aMN'nMA °a Mx J J II hn^ 0 0 GT-06546 °’ $ F GT-06910 Cl . . '•' ^YY'Ml 0 0 GT-07045 0       H MM 00 $ Cl GT-07058 Cl Mym4l hnA 0 0 GT-06547 xX'QX 0 0                     1 ¢0 Cl GT-07066 X 00              Cl GT-10411 0 H F\ / F XWX 00           1 9 Cl GT-07059 <c GT-10417 \ 0    H      V 0 0                           1 9 Cl GT-10649 XX'Xo 0 0                       | 6 -X"Xro.B 00 $ Cl GT-10650 XXXx 00                1 I Xr 0 H 0 °xX9'Ojj 00           1 9 Cl GT-10651 ll X) / ■ a X 0 GT-06465 0       H Cl GT-10652 rr’ 0 0                        1 ¢8 F GT-06460 F GT-09971 cr 00            1 Cl GT-06423 ^"XXcw 00 6 H -bvO    rr 00         T C? 0— GT-10309 0 0      \A f u GT-10653 OO             [ N 6 GT-06402 ^■XCOX^ 0 0              1 X. GT-10475 0 0                       | 0 GT-09963 xYxx 0 0 1 ¢) F GT-10655 ’Y-pX'YY 0 o             Y N u GT-10079 °° cj Cl GT-10141 "XYXx 0 0                            | Cl o o                  1 Y1 °\ GT-10142 YYY n '"'Yi GT-10085 o       H ’YYCXjO1 0 0                  1 0 GT-10130 YyYxY' GT-10091 0 0                  1 0 GT-09992 YYYxY GT-10495 YA / ' °° 6 GT-10124 YYYxY GT-10510 GT-10135 YYx '0J GT-10167 Cl GT-09972 ‘YvOYy oo               n । 0 Ay T Cl GT—06442 YXCOX 0 0 0 9 Cl GT-10143 XY'Xx 0 0                          | F GT-10173 xXYx 00                   L J. ^-"'Xl GT-10144 XYXX 0 0                            | <> Cl GT-10178 ‘XY'OxY 0 0 GT-10145 0 0                          | F GT- 06437 9.      H            fh / \         n^JO 0^ O\ 1 11 l l k xo o GT-10146 H / \ / ^kOVN'N        0 O ° \ ON JI J oOk J O" HNO         "^O^N^JxJ 0 O                           | ¢) Cl GT-10208 o      H            kff / -Vx\.N.     z?\A / 0= /    n”^ | Y ?!   [ ll OnY     Ok / V 0 o GT-10147 H                F F ° / / \ J J Lvi il hn /      vn / j 0 0                          ] / Cl GT-10298 o       H °0000 O jroj hno yo      xok 0 0 GT-10148 H                \XO / \ k / V N \   X 0=^  y-n  h  j   I / O   i i hnO       ^\Ox / OJ 0 0                          | ¢) Cl GT- 06470 °i>XCQjk °° $ Cl GT-10065 °On0lXn'O rO HO     ^vN lj 9 Cl GT-06474 9,          H AA JyX o / Jn L il l 1 L hn J / T^k °° $ F GT-10149 °9kOOOO~i rO hn /       VnJxJ 0 O                           | 9 F GT-06510 9.          H °J>Y On jO °” $ F GT-09980 °9kOOOO~9 rO O ry ^NrV Cl GT-10315 9       H ^kxok1 °° / F GT-09987 °^O^nO1XnO / rO HO ^N0r F GT-06961 0       H >--\   O X\ .N. / \    ,0, °OON010 On jO °” $ Cl GT-10615 °OJOO Oh 91 HN /       XLn kJ 0 0          Y k^ J GT-10320 9'          H .--.   Oxx.N. ^x.     .0. / oooa OnOO~ HnO Y^^f 'ky J O                  1 Vs Cl GT-10616 H / --<    --. X .N. °^^^NDTy NClk oo hnY y^ M / n jj 0 0            II hr GT-10492 9       H         \ / F / kXX k n AJ HN^ / / O^F 0 0                         1 9 Cl GT-10617 / --.-. zXzN. °o^^nOoT iT^Jk oo hn /      X?n,XJ. oo         Y F 6, GT-10493 \ 0 H \ / ° »X9XxZ 0 o               1 9 Cl GT-10618 •ww 0 0           Y Xs F Cl GT-10619 W'Y" C? Cl 0 H X#XX 0 o                     1 ¢) Cl •wo# 0 0           Y ¢) GT-06466 Cl GT-10620 l=: '•. GT-06461 XZ# F GT-10621 0 o 6 GT-10310 H / \         N X Y X °9 £nX J l i £ J ° °      F n GT-10622 w# X 0 0            Y N 6 GT-06398 •WOX 0 0              1 X GT-10241 WX- X Cl GT-06426 •WOX 0 0                  1 T F GT-10242 "XXX^a GT-06427 •Wo# ¢) Cl GT-10132 •i>XXxX GT-06428 W? ZA o / GT-10026 0 0 GT-10086 H X X V-XJ L i 1J 0 o                1 0 GT-10126 XX"Xj;:rG M -c? : .r o GT-10137 0 0 oX 0 0                  1 o GT-09974 XXXn 0 0                 n T 0 V Cl GT-10511 .1' o GT-10243 F GT- 06444 H M X NvXJ L n XJ 00        ° Jx V Cl GT-10244 xGm Cl GT-06499 H °XXXjT O jOY\ 00                   IL J ^^Cl GT-10245 ”XF / cM F GT-06500 °^XNCXX OXjX^ xo 0 GT-10246 H °XXnXX"N'iXu r°X o o F GT- 06439 h     X oX Xn            i 1 i 11 HN^T yAJ LnJ^N 0 0 GT-10247 "XG'xx Cl GT-10209 H        Yj / -v / ^vn'n-> _ / VXJ k N X N HN—<          \zNx / V1'1 0 0 GT-10248 xXXX oo            y Cl GT-10299 °^yCr 'G jc>Y 0 0 GT-10067 YXSXX r? Cl GT-06536 °° $ F GT-10249 C? F GT-06462 --- ,-.. , F GT-09982 Cl GT- 06505 H op               l J, 9 00 $ F GT-09989 ArX-Ax F GT-06501 H 00 $ F GT-10568 0^0 .■ ",. o GT-06511 H »ApAOA 00 $ Cl GT-10545 HN X                     /   \__. 0 0       F\^ GT-06502 ’Apaojx- O 0                     1 ¢) Cl GT-10546 ’ r : y o GT-10412 H    V pa       x hnX    APv O 0                       1 ¢) Cl GT-10547 F H    fA J I N-< hnH\                __ / \__. O 0 F GT-10482 \ H        \° 0 o                    1 9 Cl GT-10548 Cl H °A       JJ T [   N- / 1 hn^             'x__7 5__v Cl Op / N            1    1 Ap yAX LnJX 00 $ Cl \ 0 H oyymN'pNP hn^\                 \ X0 o           \\ 0 / »A9AOj6 0 0                    1 9 Cl GT-10569 CpO 0 ",. V o GT-06420 GT-10645 0 0                  v v GT-10311 “iq / oox! ° °       F n F GT-10647 0 0                  ^ \\ GT-06399 ^-^1^001, 0 0                  1 A F GT-10251 H     / / / --z-—         / --   \— / o / ^ / / jj i HN— /    / / O 0             / / Cl GT-09964 ¢) F GT-10252 __CH / / ci 0=( / / / J (1 N— / ' HN—(,             \__ / 0 0 GT-10080 0 0                  1 Cl GT-10133 Cl s.^ / o / / lOJ J ( HNO           _ / 0 0 0 0                  1 3 0^ GT-10028 H         NZ XN /  \                N \    / -- °4      J J i   n—' HN^ h'''^   _ / 0 0 GT-10087 0 o               J. 0 GT-10127 • H         C N , 7- / ^s.^Nx / —.  \ — / /  \                N \    / --- 0=(        J J 1 HN^ _7 0 0 GT-10092 / —Z w _ Z— / IZ <zOo '1 o GT-10138 . / 3 H           \f । '0 /  \    / ^T|   /   N   \    / b °O ON. J J 1 HN^<           \_ / xo 0 op-Xoojo 0 0                    1 o GT-09975 H     / / / —\ / >^Vn'n^\ \— / o / Vn J J 1   N- / "\ HN /            0 / / o o               V- / Cl GT-10512 GT-10253 / vX / er : \ . '1 o GT-10168 °X“rXN'OY 00 $ Cl GT-10254 H           /   \ / -z^ / aA A"a \^~ / / \ / ^X A N \  )--( o=\ / \ J J I       A H N                  X__ /      X V\ o o               \—2 Cl GT—06445 1 H °x XvXJ L N XJ hn-^ )T^     hi^ 00        o J\ V Cl GT-10255 H          (   \ / --V    / ^AXzN,       \-~ / / \ XAf X N \ / —( A    J J I  N-7 A hn—y y^xA \_ /     / / a XO O                          / F GT-10174 1 H .—.  - AA    A\ °XXnXXX OxCX-\ 0 o                                      |l .J '-""Al GT-10256 A     J J 1 nA \ hnX     a za 0 o            a / Cl GT-10179 Jx -, ^XTCI oXX“nOx OxOi^ hn^ y^A^ a^aa O 0 GT-10257 F F H           / ) / \ xy X n \ )—( <A     J J I nA \ HN                   /      / x O 0               \— / Cl GT—06440 i h        X / A aX / A NA-M °k X\XX I i A n 0 0 GT-10258 a. X °X^XXXj । naX^ HNXo^    Q Cl GT-10210 i h          Xd aa / Xyna aV A XXJ L N X N HNX        \zNx / VN 0 0 GT-10068 °k A\ J J l nA \ HNX A"A a aa 0 O            A / Cl GT-10300 X N °XX^XXX O XX<X HnX / 7^ A / n^^s XoX 0 0 GT-10259 “Xyxyxy'oJx^ F GT-06471 XXpX'OXk $ Cl GT-09983 a^yx-A A A A0 Cl GT—06467 Cl GT-09990 °<Hxyv4T hn^x^ F GT-06475 °kPyXXjX °° $ F GT-10459 H ’kXXXXjO °° 6 GT-06463 F GT-10460 “xppcrejp GT-06506 F GT-10461 ^"pO^O / X, °° 6T GT-10316 »^9^0 X) 00 $ F GT-10462 ^ya8-© / / 0 0                    1 ¢) F GT-06962 Cl GT-10463 ^pye-xr oo           1 Cl GT-10321 0 0                         1 ¢) Cl / o © .• o GT-10413 Q Cl GT—10464 “° 6 GT-10483 „ \ i H          v° ’iQ^yoy) 0 o               X ¢3 Cl GT-10521 / =z w _ "t. X o xp-y99o^S 00 $ Cl GT-10520 “° 6 °iQy9rN'Oj6 0 0                         1 9 Cl GT-10287 ■^pcrej|! Cl GT-10078 M -z—' XZ   U- O'O V o GT-10288 GT-10312 vXx ZZ^ z—' w o GT-10134 0 0 GT-09960 XX'IA 0 0             1 6, GT-10056 h        XX o<xnX nX ?xx^ HN^       VN-J^N xo o GT-09965 XXX 0 0                  1 cp F GT-10129 •^c / eja0 xo o GT-10081 xO'o# ¢) Cl GT-10139 H °XZHXXN'O Xxi HN^                    \QX 0 0 H M IO 1 I N XJ hnx       \zNyX / oo         1 °\ GT-09977 xXx 0 0            0 0-, V Cl GT-10088 ’XvliOX 0 0                 1 0 GT-10289 °XoXN<^ F GT-10093 “^XXX-0 0               1 o GT-10290 xxM °° $ Cl xxxx 0 0                  1 o GT-10291 xxM °° $ F GT-10513 X o^x \7 -n zx ^z ~z O GT-10292 xxW Cl GT-10169 Cl GT-10293 ■’X-AO'X^ 0 0                     1 ¢) Cl GT-06447 0 0              0 V Cl GT-10294 °A"?xA^r Cl GT-10175 HN^ 00              L Cl GT-10069 Cl GT-10180 °XA\XX O jOi^ hn^        x-nx / a / 0 0 GT-10295 F GT—06446 H     n A J^vX A L N A N O O GT-09985 --:? ; Cl GT-10211 H        11 .---------------. ___ 0= / \— n^T lT ? । [ ll 0 o GT-09994 : =,^ , F GT-10301 °l^NpJX?ONjqw^ 0 0 GT-10648 GT-06537 Cl GT-10563 ’■XpA " / V? GT-06539 Cl GT-10564 GT- 06538 °A9XOjX °° $ F GT-10565 0 0           xAA CJ F GT-06540 F GT-10566 H                    pi °C^yO Cl GT-06507 °iQ9CCQj|) F °l^yCr / ° GT-10317 H °° $ F GT-10478 GT-10306 °° $ Cl GT-10479 °C^yO GT-10408 O 0                       1 ¢) Cl GT-10519 °C^yO GT-10414 H    V °9          I 1 1J O 0                       1 ¢) Cl J? 00 $ Cl GT-10484 \ H     V ^yCCo91 0 o                     1 V Cl °° $ Cl xo 0 ^990.3 0 0                  1 9 Cl GT-10029 h         91 °9Z9NQCrN HN^          \l / NXz^V'1 0 0 GT-06421 49 _ z—' yjT'" 9^° o GT-10128 °^r9a9x9’" 0 0 GT-10313 ■^yro n u 0 0 GT-06400 ^pyopi, 00 y GT-09976 0 °               0 V Cl GT-10076 ° 0         il F F GT-10082 ppp / oyt 00 A Cl °° $ Cl yyy 0\ ^“pa’-^jO F GT-10089 ’iQpyCyO 00     n °° $ Cl GT-10496 00     n 0 0                   1 9 Cl 00 F        / L 0 H      V0" °<ppr®y O 0                      1 Y Cl GT-10514 »ypyCpO «pppay.jy °° $ Cl GT-10170 Cl ’pppyp-jj- F GT-06443 WX 0 0 F       °Xs V Cl GT—09984 00      ° X 9 Cl GT-10176 0 0 F                         |l J Cl GT-09991 ="- F GT-10181 .Cl °xxcxx oxx^ GT-10330 xxx GT-06438 OO  F GT-10337 XXN'X9 GT-10212 0 O F GT-10339 GT-10302 GT-10654 xX'X O 0            1 T F GT-06472 Cl GT-10340 0 0            1 9 Cl GT-06468 ^X°X ° 0 f        0 xK Q Cl 0 0            1 9 GT-06476 F GT-10430 xXX 00     6 GT—06464 XXX ° 0    F           0 9 F GT-10518 GT-06508 • '<: / ■ •1 F GT-10431 xXX 00 6 GT-10318 F GT-10232 Cl GT-06963 Cl GT-10233 GT-10409 Cl GT-10131 xo 0 GT-10415 00        Ll Cl GT-09993 q 0 a 0 GT-10485 \ H     V °PXpTOj5 00 r ¢) Cl GT-10125 0 0 Cl GT-10136 'NlQ-XH3 0 0 W'cJ 00 T ¢) Cl GT-09973 ^-pa'-px) 00         0 V Cl GT-09962 Vy    P GT-10234 xxpcrpw 0 0                         1 3 F GT-10314 0 onJ f \= / GT-10235 °°      3 Cl GT-09961 0. /          O-f HN X     HN-N N—\ Y  NlX   /   \__ /  \--. o y / / / \    AA O      / /        \=J GT-10236 y#A °° A F GT-10077 °YY      X HN A ^x HN-N H A A F GT-10237 H                      , oPPA i A r r TinA 0 0                          1 Y Cl GT-10083 Cl A HN A    HN-N  N—< A b Cl GT-10238 H           F F / —\     / Y       X °^IXnCO Ju HN X      AinAY 0 o                         1 V Cl \ °YY ^X ™Y„A hn-n ,NY Q 0 / GT-10239 H       \y0" AnaT yXX anJU O 0                          1 ¢) Cl GT-10090 °Y>    / -X HN^m^ HN-N H W o GT-10066 XA °° A Cl GT-10094 y-z a 0 oA GT-10240 «y9cAA °’ $ F °YX      P wA GT-09981 °yA A Cl GT-10515 0 oA A GT-09988 ° A ".A F GT-10171 Cl A   X H N     N       N - ° po    / / 0 YY     \_ / GT-10331 A A r~ -Z. A GT-10304 Cl 0 A      p H N N   HN -    y y7 ° aA  A o    V      \_ / GT-10334 ApaAA Cl GT-10177 °Y1 HN-N GT-09978 0          H 2 / N v ^V^n^Vi ylj ^'ny\J 0           o JC V Cl GT-10182 °Y1       / -A HN.A,. HN-N N^ Cl GT-10061 Cl GT-10183 : GT-09986 0          H .- ? Cl GT-10296 °n hn-H^-^hn-n n—n —N GT-10477 ZI Oh cl ^=z GT-10303 HN^Xn   HN-N_^N—y 0 J— O^A_ /   Ha 11 GT-10332 ° o F hnO            no °oopu CW GT-10487 Cl °ri       K HN'>H'nA hn-n n-a \= / GT-10335 0 0 F hnW KAW °HyCr on Cl GT-10489 Cl °ri         o r\ HN>H'N--\ HN- N nA \= / ° o^o   Ac GT-10057 00  ? H JN \ W'H Cl GT-10488 ■ 0 •I GT-10062 nOlaH Cl GT-10490 T O A & z u / '•O. GT-10059 ° 0       H «^110^0- Cl GT-10305 T O & z Ci ^Q, GT-10333 vC _ w IZ 7 o GT-10319 °Yb       / ~A fS hnV^'n'A hn-n n~\ )= / o A~ / \ axA    \ / -      O = GT-10336 0 0       u HN^ ;C<VR'nY bb ob>yQ Cl GT-10307 Cl °Yb       A HN~N n~A / = / 0 oa2 (2 -      0= GT-10058 ° o       H °Y>yU U J3 0 F       ° Jy 9 Cl GT-10410 Cl °vb       / -a Q GT-10063 0 0       H HN^            y^Z ”   b Y Cl GT-10416 Cl A       fi, HN>An-\ HN~N        / = / 0             \~J FT GT-10060 00    H 29 v h'V'NZ - A A. Cl GT-10486 Cl / -A hn-n n~a o Aa\   2\ <21 /    \) 0 GT-10172 p,-Y GApcY cp 0 d                      i. Cl °Tb       A hnY=n=\ hn-n n~\ / = / 0 c / a2 a) GT-10491 aV Cd              C| Cl A   A HNA-N-\ HN-N        / = / ° \ / GT-10070 0 0      nJ HNb K^x     I ,NA °b / Nbjf i — a\Y\ nJ Y ' J                 b.N 0       H GT-06863 Y Q >° o ‘k o GT-08034 H            H A“A AYb’bb A Y a nAJ a aj HN A 11^        J 00        ¢5 Cl GT- 06864 b z^ '—z —z / , A o GT-08040 O        h           h aa Kayn-na A Y AAA A Ab hnA                 | °°        ¢1 Cl GT-06865 b G —z A o GT-09709 1 H °<2<A C J 2 hnA      ANAAb0 / 0 0 GT-09741 1 H aa aV-na । hng      ^nyyg । 00      o LYY Compounds of Formula (I’)

[0072] The present disclosure provides a compound of Formula (I’) (I’) or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers and diastereoisomers), solvates, isotopically enriched analogs, or polymorphs thereof, wherein Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, R1, R2, ring A1, (Rd1)n1, Re, and Rf are as defined in the compounds of Formula (I’) above and the various embodiments thereof.

[0073] In some embodiments of the compound of Formula (I’) of the present disclosure, Ra1, Ra2, Ra3, and Ra4 are identical or different and each independently represents H, deuterium (i.e., D), halogen (e.g., fluorine, chlorine, bromine, or iodine), C1-6 alkyl (e.g., C1-3 alkyl, such as methyl, ethyl, or propyl), halogenated C1-6 alkyl (e.g., halogenated C1-4 alkyl, such as trifluoromethyl), deuterated C1-6 alkyl, C1-6 alkoxy (e.g., C1-4 alkoxy, such as methoxy), deuterated C1-6 alkoxy, or halogenated C1-6 alkoxy (e.g., halogenated C1-4 alkoxy, such as trifluoromethoxy). In some subembodiments of the present disclosure, Ra1, Ra2, Ra3, and Ra4 each independently represent H.

[0074] In some embodiments of the compound of Formula (I’) of the present disclosure, Z represents C(O), CH2, or CD2.

[0075] In some embodiments of the compound of Formula (I’) of the present disclosure, Z represents C(O).

[0076] In some embodiments of the compound of Formula (I’) of the present disclosure, Z represents CH2.

[0077] In some embodiments of the compound of Formula (I’) of the present disclosure, Z represents CD2.

[0078] In some embodiments of the compound of Formula (I’) of the present disclosure, (Ra5)m indicates that the isoindoline ring in Formula (I’) to which it is attached is optionally substituted with m Ra5 groups, wherein each Ra5 is identical or different and independently represents deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl (e.g., C1-5 alkyl, C1-4 alkyl, or C1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C1-6 alkyl (e.g., halogenated C1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), deuterated C1-6 alkyl (e.g., perdeuterated C1-6 alkyl, perdeuterated C1-5 alkyl, or perdeuterated C1-4 alkyl, such as CD3, CD3CD2-, CD3CD2CD2- etc.), C1-6 alkoxy (e.g., C1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, or tert-butoxy), deuterated C1-6 alkoxy, halogenated C1-6 alkoxy (e.g., halogenated C1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-), C2-6 alkenyl (e.g., vinyl), C2-6 alkynyl (e.g., ethynyl), or heterocyclyl (e.g., 4- to 30-membered heterocyclyl, 4- to 20-membered heterocyclyl, and 4- to 15membered heterocyclyl), wherein said heterocyclyl is optionally substituted with one or more (e.g., 1-10, 1-6, 1-3, or 1) substituents independently selected from the group consisting of halogen, C1-6 alkyl, and tert-butoxycarbonyl, and m represents an integer of 0, 1, 2, or 3. In some subembodiments of the present disclosure, m represents an integer of 0, 1, or 2. In some subembodiments of the present disclosure, each Ra5 is identical or different and independently represents deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, mercapto, nitro, amino, cyano, C1-4 alkyl (e.g., C1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, secbutyl, or tert-butyl), halogenated C1-4 alkyl (e.g., halogenated C1-3 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), C1-4 alkoxy (e.g., C1-3 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, secbutoxy, or tert-butoxy), halogenated C1-4 alkoxy (e.g., halogenated C1-3 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-), or 4- to 15-membered heterocyclyl (e.g., piperazinyl), wherein said 4- to 15-membered heterocyclyl is optionally substituted with one or more (e.g., 1-10, 1-6, 13, or 1) substituents independently selected from the group consisting of halogen, C1-6 alkyl, and tert-butoxycarbonyl.

[0079] In embodiments of the compound of Formula (I’) of the present disclosure, the number of substituents is not theoretically limited in any way, or is automatically limited by the size of the building units.

[0080] In some embodiments of the compound of Formula (I’) of the present disclosure, ring A1 represents heterocyclylene containing at least two nitrogen atoms, e.g., 4- to 30-membered, 4- to 20-membered, or 4- to 15-membered heterocyclylene. Ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1- 6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20 (e.g., an integer of 0-10).

[0081] In some embodiments of the compound of Formula (I’) of the present disclosure, ring A1 represents 4- to 30-membered heterocyclylene containing at least two nitrogen atoms (including 4- to 25-membered heterocyclene, 4- to 20-membered heterocyclene, 4- to 15-membered heterocyclene, and 5- to 20-membered heterocyclene). Ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl (e.g., C1-5 alkyl, C1-4 alkyl, or C1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), deuterated C1-6 alkyl (e.g., perdeuterated C1-6 alkyl, perdeuterated C1-5 alkyl, or perdeuterated C1-4 alkyl, such as CD3, CD3CD2-, CD3CD2CD2- etc.), halogenated C1-6 alkyl (e.g., halogenated C1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), C1-6 alkoxy (e.g., C1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, or tert-butoxy), or halogenated C1-6 alkoxy (e.g., halogenated C1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-), and n1 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

[0082] In some embodiments of the compound of Formula (I’) of the present disclosure, ring A1 represents 1,3-diazetidinylidene, imidazolidylene, pyrazolidylene, piperazinylene, diazacycloheptanylene,          diazacyclooctylene,          diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene, diazabicyclo[2.2.2]octanylene, 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonanylene, 2,8-diazaspiro[4.5]decanylene, 3,9-diazaspiro[5.5]undecanylene, or octahydropyrrolo[3,4-c]pyrrolylene, each being optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl (e.g., C1-5 alkyl, C1-4 alkyl, or C1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, secbutyl, tert-butyl, pentyl, or hexyl), deuterated C1-6 alkyl, halogenated C1-6 alkyl (e.g., halogenated C1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), C1-6 alkoxy (e.g., C1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, or tert-butoxy), or halogenated C1-6 alkoxy (e.g., halogenated C1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-), and n1 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

[0083] In some embodiments of the compound of Formula (I’) of the present disclosure, R1 represents a bond, and R2 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl (e.g., methyl, ethyl, and propyl); wherein said groups are optionally substituted with a substituent selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, and C2-6 alkenyl.

[0084] In some embodiments of the compound of Formula (I’) of the present disclosure, R1 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl optionally substituted with one or more substituents independently selected from the group consisting of optionally substituted aryl (e.g., C5-30 aryl, C5-20 aryl, and C5-15 aryl) and optionally substituted heteroaryl (e.g., 5- to 30membered heteroaryl, 5- to 20-membered heteroaryl, and 5- to 15-membered heteroaryl), and R2 represents a bond. In some embodiments of the compound of Formula (I’) of the present disclosure, Rw represents hydrogen or C1-3 alkyl (e.g., methyl, ethyl, and propyl), wherein the C1-3 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of: phenyl or naphthyl, each of which is optionally substituted with one or more (e.g., 1-7, 1-5, 1-4, 1-3, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl; and furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl,                  2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl,      3,4-dihydro-2H-benzo[b][1,4]oxazinyl,      quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl,      1H-pyrrolo[2,3-b]pyridinyl,     pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each of which is optionally substituted with one or more (e.g., 1-10, 1-7, 1-5, 1-4, 1-3, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl; and / or

[0085] In some embodiments of the compound of Formula (I’) of the present disclosure, R1 rytO represents N(Rw), wherein Rw represents H or       ■■ , and R2 represents a bond.

[0086] In some embodiments of the compound of Formula (I’) of the present disclosure, Re represents a bond. In some embodiments of the compound of Formula (I’) of the present disclosure, Re represents C(O)O.

[0087] In some embodiments of the compound of Formula (I’) of the present disclosure, Re represents the structure of the following formula: (Re2)m2 (Re3)m3 wherein Re1 represents C(O), CH2, or halogenated CH2; ring D represents arylene, and (Re2)m2 indicates that the ring D is optionally substituted with m2 Re2 groups, wherein each Re2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m2 represents an integer of 0-20; and ring E represents nitrogen-containing heterocyclylene, m4 represents an integer of 0 or 1, and (Re3)m3 indicates that the ring E is optionally substituted with m3 Re3 groups, wherein each Re3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m3 represents an integer of 020; and symbol # indicates the point of attachment to Rf .

[0088] In some embodiments of the compound of Formula (I’) of the present disclosure, ring D represents C5-30 arylene, examples of which include but are not limited to C5-20 arylene, C6-20 arylene, C5-15 arylene, and C6-15 arylene, e.g., phenylene and naphthylene. The arylene is optionally substituted with m2 (e.g., an integer of 0-20, or an integer of 0-10, such as 1-6, 1-4, 1-3, 2-6, or 1) substituents Re2 independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, C2-6 alkynyl, and C2-6 alkenyl.

[0089] In some embodiments of the compound of Formula (I’) of the present disclosure, m4 represents an integer of 1, and ring E represents 4- to 30-membered nitrogen-containing heterocyclylene, examples of which include but are not limited to 4- to 20-membered, 4- to 15membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, and 5- to 9-membered nitrogen-containing heterocyclylene, e.g., azetidinylene, pyrrolidinylene, imidazolidylene, pyrazolidylene, piperidinylene, piperazinylene, tetrahydropyridinylene, dihydroxypiperidinylene, difluoropiperidinylene, azepanylene, azacyclooctylene, diazacycloheptanylene (e.g.,  1,4- diazacycloheptanylene,        4,5-diazacycloheptanylene,         1,3-diazacycloheptanylene), diazacyclooctylene, nitrogen-containing bridged heterocyclylene (e.g., 6- to 20-membered nitrogen-containing bridged heterocyclylene, such as 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene,             3,6-diazabicyclo[3.1.1]heptanylene,             3- azabicyclo[3.2.1]octanylene,               3,8-diazabicyclo[3.2.1]octanylene,               2,5- diazabicyclo[2.2.2]octanylene, and quinuclidinylene), azaspirocycloalkylene (e.g., 5- to 20membered azaspirocycloalkylene, such as 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonanylene, 2,8-diazaspiro[4.5]decanylene, 3,9-diazaspiro[5.5]undecanylene, 3-azaspiro[5.5]undecanylene, and 7-azaspiro[3.5]nonanylene), and octahydropyrrolo[3,4-c]pyrrolylene. The heterocyclylene is optionally substituted with m3 (e.g., 0-20, such as 1-20, 115, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents Re3 independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, and C2-6 alkenyl.

[0090] In some embodiments of the compound of Formula (I’) of the present disclosure, Re represents            or o '—' '—    , wherein symbol # indicates the point of attachment to Rf .

[0091] In some embodiments of the compound of Formula (I’) of the present disclosure, Rf represents C1-10 alkyl, examples of which include but are not limited to, e.g., C1-10 alkyl, C1-9 alkyl, C1-8 alkyl, C1-7 alkyl, C1-6 alkyl, C1-5 alkyl, C1-4 alkyl, C1-3 alkyl, C1-2 alkyl, and methyl, e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert pentyl, hexyl, heptyl, octyl, nonyl, and decyl. The C1-10 alkyl is optionally substituted with one or more (e.g., 1-20, such as 1-18, 1-15, 1-10, 1-6, 1-5, 1-4, 1-3, 1-3, 2-6, or 1) substituents independently selected from the group consisting of: halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally substituted aryl (e.g., optionally substituted C5-30 aryl, optionally substituted C5-20 aryl, or optionally substituted C5-15 aryl), optionally substituted heteroaryl (e.g., optionally substituted 5- to 30-membered heteroaryl, optionally substituted 5- to 20-membered heteroaryl, or optionally substituted 5- to 15-membered heteroaryl), optionally substituted heterocyclyl (e.g., optionally substituted 4- to 30-membered heterocyclyl, optionally substituted 4- to 20-membered heterocyclyl, or optionally substituted 4- to 15-membered heterocyclyl), optionally substituted cycloalkyl (e.g., optionally substituted C3-30 cycloalkyl, optionally substituted C3-20 cycloalkyl or optionally substituted C3-15 cycloalkyl), and NR3R4, where R3 and R4 each independently represents H, C1-3 alkyl, or optionally substituted cycloalkyl (e.g., optionally substituted C3-30 cycloalkyl, optionally substituted C3-20 cycloalkyl or optionally substituted C3-15 cycloalkyl). In some embodiments, examples of aryl include, but are not limited to, C5-30 aryl, C5-20 aryl, C6-20 aryl, C5-15 aryl, and C6-15 aryl, e.g., phenyl and naphthyl. In some embodiments, the aryl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-7, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl. In some embodiments, examples of heteroaryl include, but are not limited to, 5- to 30-membered heteroaryl, 5- to 20-membered heteroaryl, 5- to 15-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7membered, and 5- to 6-membered heteroaryl, e.g., furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl. In some embodiments, the heteroaryl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-7, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl. In some embodiments, examples of heterocyclyl include, but are not limited to, 4- to 30-membered heterocyclyl, 4- to 20-membered heterocyclyl, 4- to 15membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, and 5- to 9-membered heterocyclyl, e.g., azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, pyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxy-piperidinyl, difluoro-piperidinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, dioxacyclohexyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl, 4,5-diazacycloheptanyl, and 1,3-diazacycloheptanyl), diazacyclooctyl, bridged heterocyclyl (e.g.,  6- to 20-membered bridged heterocyclyl, such as 6- azabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2.2.2]octanyl, and quinuclidinyl), azaspirocycloalkyl (e.g., 5- to 20-membered azaspirocycloalkyl, such as 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl, and 7-azaspiro[3.5]nonanyl), and octahydropyrrolo[3,4-c]pyrrolyl. In some embodiments, the heterocyclyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tert-butoxycarbonyl, and Rh. The Rh represents optionally substituted C5-15 aryl, examples of which include but are not limited to C5-12 aryl, C6-12 aryl, and C6-10 aryl, e.g., phenyl and naphthyl. The C5-15 aryl is optionally substituted with one or more (e.g., 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy. In some embodiments, examples of cycloalkyl include, but are not limited to, C3-30 cycloalkyl, C3-20 cycloalkyl, C3-15 cycloalkyl, C3-11 cycloalkyl, C5-15 cycloalkyl, and C7-15 cycloalkyl, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spiro-cycloalkyl (e.g., C5-C15 spiro-cycloalkyl, C5-C20 spiro-cycloalkyl, or C5-C25 spiro cycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, and spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C15 bridged cycloalkyl, C6-C20 bridged cycloalkyl, C6-C25 bridged cycloalkyl, and C7-C15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl). In some embodiments, the cycloalkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tert-butoxycarbonyl, and Rh, wherein Rh represents optionally substituted C5-15 aryl, examples of which include but are not limited to C5-12 aryl, C6-12 aryl, and C6-10 aryl, e.g., phenyl and naphthyl, wherein the C5-15 aryl is optionally substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy.

[0092] In some embodiments, R3 and R4 each independently represent H, C1-3 alkyl, or optionally substituted cycloalkyl (e.g., optionally substituted C3-30 cycloalkyl, optionally substituted C3-20 cycloalkyl, or optionally substituted C3-15 cycloalkyl). In some embodiments, examples of cycloalkyl include, but are not limited to, C3-30 cycloalkyl, C3-20 cycloalkyl, C3-15 cycloalkyl, C5-15 cycloalkyl, and C7-15 cycloalkyl, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spiro-cycloalkyl (e.g., C5-C15 spiro-cycloalkyl, C5-C20 spiro-cycloalkyl, or C5-C25 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, and spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C15 bridged cycloalkyl, C6-C20 bridged cycloalkyl, C6-C25 bridged cycloalkyl, and C7-C15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl). In some embodiments, the cycloalkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tert-butoxycarbonyl, and Rh, wherein Rh represents optionally substituted C5-15 aryl, examples of which include but are not limited to C5-12 aryl, C6-12 aryl, and C6-10 aryl, e.g., phenyl and naphthyl, wherein said C5-15 aryl is optionally substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy. In some embodiments, R3 represents H, and R4 represents bridged cycloalkyl (e.g., C6-C15 bridged cycloalkyl, C6-C20 bridged cycloalkyl, C6-C25 bridged cycloalkyl, and C7-C15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl), which is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, and tert-butoxycarbonyl.

[0093] In some embodiments of the compound of Formula (I’) of the present disclosure, examples of Rf include, but are not limited to: methyl, isopropyl, tert-butyl,

[0094] Preferably the compounds of the present invention and their salts (especially pharmaceutically acceptable salts, such as hydrochloride, etc.), enantiomers, diastereomers, solvates, or polymorphs thereof in Table 2 below are provided: Table 2. The compounds of the present invention Compoun d No. Structure of the compounds Compoun d No. Structure of the compounds GT-08644 H hn^ yA^ A^ O 0 GT-09135 0 H / \ / < N / —IT N > 0=CbNpU       o o GT-08881 yxW, HNA 0 0                       1 GT-09197 / :, • o GT-09018 o^A'fl hn^; y-M 0 0                      1 GT-09198 °      H yA J / N \                 )=7 O^y^N 0 GT-09057 y'-N-' hn'NlA o=^ )^N Jj J hn^ y^^^ 0 0 GT-09199 0 H o GT-08880 y^N''^ hA’A 0=^ yN J J hn^ y^^-^ 0 0 GT-09200 y y - GT-09138 y^N'''^ xN. J HN 0=( AN J J hn—( y^^^ 0 0 GT-09201 0          H _ /  \   / '^^V N 00   0 iT  N  0 0=(    )— N             I I              I \   /            ky, n / / -0 / / 0 GT-08531 c ZI 0 / GT-09202 0       H HN^y                         ^- / ^ GT-08710 9'          H °<YXr"'C0 HN^         \ / Ny^ 0 o                     1 GT-09203 000-11^ 0     P N / -- /  - / °^r^N GT-08711 o       h o^^Lyf O / hn^< 0 o                     1 GT-09213 0 "y^o ^yyr^ 0 GT-09058 y^N^ 0 HN 0=( / -N J] J HN—(   / 7^^ 0 0 GT-09104 H / / -0-N /       h 00 0000 ___« / / / / / 001 HN-0 0 OO GT-08866 ,N. J 0 HN 0=( )—N jj J HN—( 0 0 GT-09105 H 0-0                         H r~^ ^\X-J k^u.^\ / ^ / -^ / N\(zy hn-0 00 GT-08865 0 0=(     N J] J hn—( y^^^ 0 0 GT-09106 H „ / 00    H 00 / 000 0« / / / - / N009 HN-0 fl        F OO GT-09917 0       H O 0 GT-09107 H 0-0                         H r~^ o=< ACL J hn—4                            ^-02^ 0 0 F GT-09918 0       H / --\L , / 0 Nx / / oy yN'yy 7^0 HNy rY --N-r o 0 (L GT-09108 hnC n N—\ H                     H o000N'O / -^x / Nyn 00 00- / -^  ^07 GT-09919 0 H 0. GT-09109 H«0° / 0 / 0=( yN- JI J 0-0 \              d r^. \_ / 0^--^      n ., / 00 / ^ n -yyy GT-10465 OuO o                1 0N \ / 000^'00 00 O / 0N            1      1 V / ^-00 0N0 / N 0                1 6 GT-09110 0           H HNy / ^00 / R'N<0 o=C0yu VN / / - / / ^p GT-10476 C\O /  \          I N \         , °a an h J        r 7 HN—"^A / N^J^N 0 0                        | 0 GT-09111 0          H oX NpJ Xh     H GT-10480 y. o GT-09112 0                       HN-—ULX hnX         h              / —' L^--^ ox V / X-XX        / — / X_ / ~~N II 7 N^X >-- / XxX i^^ / NX GT-10646 X X JX^Ja O °<XX1 HNX           \__ /  \_. 0 O GT-09113 ° H HNX' rvzXz^kiX “XXpj GT-09129 H °^jnAJ l n XJ X hnx^     x^xx x 0 0 GT-09114 0           U JNX ^xkV^N'Vi        u 0XXyU GT-09130 1 H / \ / x9x<n'n''X ^'r<^N^"i °^ x\ ii l m k J I h\^ y-xx vxv o 0 0 GT-09115 0 H HnX 7-^^xxN-m-^W o=XNpX GT-09131 1 .■ "7 . o GT-09116 00    H H / N^ kxXrR'N^X OX XN 1    1    1    1                 H ,-7-. yU XxNn^tzx GT-09132 H / \ / ^x:yxN'NX^ Xxxx °^>AJ l n XJ l J HN X / / T^ XN^XX X 0 0    F GT-09117 ° o        H °x               | | 1                 H \__ / X '-^''F 0 GT-09133 O\^ /  )            ___XNZ\ HN J               / X \ ? YA     H / —^   \ V ° x / Ox °'xj GT-07990 Boc H                         । aa xXyn'nX rX x XvJ XXJ 00 Cl GT-09134 -- o GT-07996 _                       Boc O            H                 । AA Sx-n^x rX 0=^ x NXX XnXx HN\.                       1 00 Cl GT-09708 O 0              0 UN-XX'A. X'n^XX °OnCQ ,o Ll.-, X ' '         N           N X XX F H     XXJ 9 Cl II. Other Forms of Compounds (including salts, enantiomers, stereoisomers, solvates, isotopically enriched analogs, or polymorphs of compounds)

[0095] The compounds of the present disclosure have the structures of any one of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’). Unless otherwise specified, all references to the compounds of the present disclosure also include compounds of any one of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’) and specific compounds within the scope of these general formulae.

[0096] It should be recognized that compounds of the present disclosure (including compounds of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) may have a stereoconfiguration and thus can exist in more than one stereoisomeric form. The present disclosure also relates to optically enriched compounds having a stereo-configuration, e.g., greater than about 90% enantiomeric / diastereomeric excess ("ee"), such as about 95% ee or 97% ee, or greater than 99% ee, and mixtures thereof, including racemic mixtures. As used herein, "optically enriched" means that a mixture of enantiomers consists of a significantly greater proportion of one enantiomer, and can be described by enantiomeric excess (ee%). Purification of isomers and separation of mixtures of isomers can be accomplished by standard techniques known in the art (e.g., column chromatography, preparative TLC, preparative HPLC, asymmetric synthesis (e.g., by using chiral intermediates) and / or or chiral resolution, etc.).

[0097] In some embodiments, polymorphs forms or salts of the compounds of the present disclosure (including compounds of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) are also provided. The salts may be pharmaceutically acceptable salts, including but not limited to hydrohalides (including hydrochlorides, hydrobromides), sulfates, maleates, sulfonates, citrates, lactates, lactobionates, L-tartrates, fumarates, L-malates, L-lactates, a-Ketoglutarates, hippurates, D-glucuronates, D-gluconates, a-D-glucoheptonates, glycolates, mucates, L-ascorbates, orotates, picrates, glycinates, alaninates, argininates, cinnamates, laurates, pamoates, sebacates, benzenesulfonates, methanesulfonates, ethanesulfonates, edisylates, formates, acetates, 2,2-dichloroacetates, trimethylacetates, propionates, valerates, palmitates, triphenylacetates, 2-ethylsuccinates, iodates, niacinates, L-pyroglutamates, L-prolinates, ferulates, 2-hydroxyethanesulfonates, nitrates, gentisates, cholates, salicylates, terephthalates, glutarates, adipates, stearates, oleates, undecenoates, camphorates, camphorsulfonates, dodecyl sulfonates, phosphates, thiocyanates, dihydrophosphates, pyrophosphates, metaphosphates, oxalates, carbonates, malonates, benzoates, mandelates, succinates, pyruvates, para chlorobenzenesulfonates, 1,5-naphthalenedisulfonates, 3-hydroxy-2-naphthoates, 1-hydroxy-2-naphthoates, 2-naphthalenesulfonates, trifluoroacetate, glycolate, or 4-methylbenzenesulfonate etc. The compounds of the present disclosure can exist as non-solvated or solvated forms in pharmaceutically acceptable solvents such as water, ethanol, and the like. In some embodiments, the compounds of the present disclosure can be prepared as prodrugs or precursor drugs. Prodrugs can be converted into parent drugs in the body to play their role. In some embodiments, isotopically-labeled compounds of the present disclosure are also provided, examples of which include deuterium (D or 2H). III. Pharmaceutical Compositions / Formulations

[0098] In some embodiments, the present disclosure provides a pharmaceutical composition comprising as active ingredient the compound of the present disclosure (the compound of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, polymorph, stereoisomer (including enantiomer), or mixture of stereoisomers thereof, and at least one pharmaceutically acceptable carrier.

[0099] In some embodiments, pharmaceutically acceptable carriers include, but are not limited to, fillers, stabilizers, dispersants, suspending agents, diluents, excipients, thickeners, colorants, solvents, or encapsulating materials. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation (including the compounds useful in the present disclosure) and not injurious to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository wax; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; surfactant phosphate buffer solution; polyethylene oxide, polyvinylpyrrolidone, polyacrylamide, poloxamer; and other common non-toxic compatible substances used in pharmaceutical formulations.

[0100] The pharmaceutical composition of the present disclosure can further comprise at least one second therapeutic agent, e.g., an anticancer agent. The second therapeutic agent may be used in combination with the compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure to treat the diseases or disorders as disclosed herein. The second therapeutic agent includes, but is not limited to, chemotherapeutic agents, immunotherapeutic agents, gene therapy agents, and the like.

[0101] The pharmaceutical composition of the present disclosure comprising, as an active ingredient, the compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or a pharmaceutically acceptable salt thereof can be formulated into any suitable formulations such as sprays, patches, tablets (such as conventional tablets, dispersible tablets, orally disintegrating tablets), capsules (such as soft capsules, hard capsules, enteric-coated capsules), dragees, troches, powders, granules, powder injections, suppositories, or liquid formulations (such as suspensions (e.g., aqueous or oily suspensions), solutions, emulsions, or syrups), or conventional injection dosage forms such as injectable solutions (e.g., sterile injectable solutions formulated according to methods known in the art using water, Ringer's solution, or isotonic sodium chloride solution or the like as a vehicle or solvent) or lyophilized injectable formulation and the like, depending upon a suitable route of administration (including, but not limited to, nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, intrapleural administration, intraperitoneal administration, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration, and intravenous administration). Those skilled in the art can also formulate the compounds of Formula (I) of the present disclosure into conventional, dispersible, chewable, orally disintegrating or rapidly dissolving formulations, or sustained-release capsules or controlled-release capsules as needed.

[0102] The compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure, as an active ingredient, is contained in the pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver to a subject a therapeutically effective amount for the indication to be treated, without causing serious toxic effects in the subject treated. A dosage of the active compound for all diseases or disorders mentioned herein ranges, for example, from about 5ng / kg to 500mg / kg, from about 10ng / kg to 300mg / kg per day, such as from 0.1 to 100 mg / kg, or from 0.5 to about 25mg per kilogram body weight of the subject per day.

[0103] The compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or pharmaceutically acceptable salts thereof may be conveniently administered in any suitable unit dosage form. Suitable unit dosage form specifications include, but are not limited to, less than 1mg, 1mg to 3000mg, 5mg to 1000mg, for example, 5 to 500mg, 25 to 250mg of active ingredient per unit dosage form. IV. Kits / Packaged Products

[0104] The compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, polymorph, stereoisomer (including enantiomer), or mixture of stereoisomers thereof is used as a medicament. The medicament of the present disclosure or the pharmaceutical composition of the present disclosure may be presented in a kit / packaged product. The kit / packaged product may include a package or container including, but not limited to, ampoules, blister packs, pharmaceutical plastic bottles, vials, pharmaceutical glass bottles, containers, syringes, laminated flexible packaging, co-extruded film infusion containers, test tubes and dispensing devices, and the like. The kit / packaged product may contain instructions for use of the product. V. Methods and Uses

[0105] The compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, polymorph, stereoisomer (including enantiomer), or mixture of stereoisomers thereof can be used as a medicament. Especially the compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, polymorph, stereoisomer (including enantiomer), or mixture of stereoisomers thereof can be used for the manufacture of a medicament for the prevention and / or treatment of diseases or disorders associated with cereblon protein.

[0106] The disease or disorder associated with cereblon protein is selected from the group consisting of: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure, and diabetes.

[0107] The disease or disorder associated with cereblon protein is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplantation-related cancer; neutropenia; leukemia, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myelogenous leukemia, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, leukemia-associated anemia, B-cell acute lymphoblastic leukemia, T-cell lymphocytic leukemia, T-cell acute lymphoblastic leukemia, lymphoma cell leukemia, monocytic leukemia, myelomonocytic leukemia; lymphoma, including diffuse large B-cell lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20 positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt’s lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin’s lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin’s lymphoma, refractory B-cell non-Hodgkin’s lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin’s lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer; inflammatory myofibroblastoma; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; ovarian cancer; bronchial cancer; prostate cancer; breast cancer, including triple negative breast cancer, sporadic breast cancer, and patients with Cowden syndrome; pancreatic cancer; central nervous system tumor; neuroblastoma; glioma; peripheral neuroepithelioma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumors; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; metrocarcinoma; head and neck cancer; brain cancer; oral cancer; sarcoma, including rhabdomyosarcoma, various lipogenic tumors, Ewing’s sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; cholangiocarcinoma; bone cancer; cervical cancer; skin cancer; Richter syndrome (RS); sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren’s syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type I diabetes mellitus, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including Crohn’s disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, acquired immunodeficiency syndrome (AIDS), COVID-19 novel coronavirus infection, gram-negative bacteria infection, gram-positive bacteria infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplantation rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular diseases (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ dysfunction caused by cachexia and septic shock; and acute liver failure.

[0108] The present disclosure provides a method for preventing and / or treating a disease or disorder associated with cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of the compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of the present disclosure comprising as an active ingredient the compounds of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or a pharmaceutically acceptable salt thereof.

[0109] In the method for preventing and / or treating a disease or disorder associated with a cereblon protein, the compound of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or the pharmaceutical composition comprising as an active ingredient the compound of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure is administered to the subject through at least one mode of administration selected from the group consisting of nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration, peritoneal administration, intramuscular administration, subcutaneous, transdermal, epidural, intrathecal, and intravenous administration.

[0110] The term "treatment" or "treating" refers to administering to a subject the compound of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising, as an active ingredient, the compound of Formula (I) (or a compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) of the present disclosure or a pharmaceutically acceptable salt thereof, to mitigate (alleviate) undesirable diseases or conditions, such as the development of a cancer or tumor. The beneficial or desired clinical results of the present disclosure include, but are not limited to: alleviating symptoms, reducing the severity of the disease, stabilizing the state of the disease, slowing down or delaying the progression of the disease, improving or alleviating the condition, and alleviating the disease.

[0111] A "therapeutic effective amount" of the compound of the present disclosure depends on a variety of factors, including the activity of the specific compound used, the metabolic stability of the compound and the duration of its action, the age, sex and weight of the patient, the patient's current medical condition, the route and duration of administration, the excretion rate, the combined administration of additional drugs, and the progression of the diseases or conditions of the patient being treated. Those skilled in the art will be able to determine appropriate dosages based on these and other factors.

[0112] It is to be understood that the choice of using one or more active compounds and / or compositions and their dosage depends on the basic situations of the individual (which should generally render the individual situation to achieve the best effect). Dosing and dosing regimens should be within the ability of those skilled in the art, and the appropriate dosage depends on many factors including the knowledge and ability of the physicians, veterinarians or researchers (see e.g., Jun Li (chief editor), "Clinical Pharmacology", 4th edition, People’s Public Health Press, 2008).

[0113] As used herein, the term “patient” or “subject” to be treated refers to animal, for example mammal, including but not limited to primate (such as human being), cow, sheep, goat, horse, dog, cat, rabbit, guinea pig, rat, mice, etc. VI. Preparation Method

[0114] The present disclosure also provides a method for preparing the compound of Formula (I), comprising using a compound of Formula (M1) and a compound of Formula (M2) as starting materials to obtain the compound of Formula (I): (M1) (Rd2>n2 (Rds)n3 (M2) (I) wherein Ra1, Ra2, Ra3, Ra4, (Ra5)m, Z, R, ring B, ring C, (Rd2)n2, (Rd3)n3, and m1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof; and LE Rw3 represents CHO, COOH, or R ?  , wherein Rc2 is as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof, and the group LE represents Cl, Br, I, OMs, OTs, or ONs; wherein (1) -Rw1-Rw2 represents       (Rdi)m , and R represents       (Rdi)m ; or 4-N At N-NH2 (2) -Rw1-Rw2 represents (Rdi )n-i 4-r(zp-N-| and R represents (Rdi)m ; or (3) -Rw1-Rw2 represents -NH-NH2, and R represents -NH-NH-; or (4) -Rw1-Rw2 represents (Rd4)n4 and R represents (Rd4)n4 wherein Rw, ring A1, (Rd1)n1, ring A2, and (Rd4)n4 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof; wherein when Rw3 represents CHO, Rc3 and Rc4 represent H; or when Rw3 represents COOH, Rc3 and Rc4 together form a carbonyl group; or LE when Rw3 represents R=2   , Rc3 represents H, and Rc4 represents Rc2.

[0115] In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, when Rw3 represents CHO, the compound of Formula (M1) and the compound of Formula (M2) undergo a reductive amination reaction to prepare the compound of Formula (I), wherein Rc3 and Rc4 in the compound of Formula (I) represent H.

[0116] In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, the reductive amination reaction can be carried out in the presence of sodium triacetoxyborohydride and an organic solvent (e.g., 1,2-dichloroethane, N,N-dimethylformamide, or dichloromethane) at a temperature ranging from room temperature to 80 oC (e.g., 40 oC to 60 oC, 40 oC to 50 oC, or 50 oC to 60 oC). Alternatively, the reductive amination reaction can be carried out in the presence of sodium borohydride and 1,4-dioxane at a temperature ranging from room temperature to 80 oC (e.g., 40 oC to 60 oC, 40 oC to 50 oC, or 50 oC to 60 oC). In some embodiments, the molar ratio of the compound of Formula (M1) to the compound of Formula (M2) can be, for example, from 1.0 to 2:1, 1:1.0 to 2, 1:1.1 to 2, 1:1.1 to 1.5, 1:1.1 to 1.2, or 1:1.2 to 1.3, and the like.

[0117] In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, when Rw3 represents COOH, the compound of Formula (M1) and the compound of Formula (M2) undergo an amide condensation reaction to prepare the compound of Formula (I), wherein Rc3 and Rc4 in the compound of Formula (I) together form a carbonyl group.

[0118] In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, the amide condensation reaction can be carried out in the presence of e.g., HATU / DIEA / DMF, or HATU / TEA / DMF, or HOAt / EDCI / TEA / DCM at room temperature. In some embodiments, the molar ratio of the compound of Formula (M1) to the compound of Formula (M2) can be, for example, from 1.0 to 2:1, 1:1.0 to 2, 1:1.1 to 2, 1:1.1 to 1.5, 1:1.1 to 1.2, or 1:1.2 to 1.3, and the like.

[0119] In some embodiments of the method for preparing the compound of Formula (I) in the LE present disclosure, when Rw3 represents R>=2  , the compound of Formula (M1) and the compound of Formula (M2) undergo an aminoalkylation reaction to give the compound of Formula (I), wherein in the compound of Formula (I), Rc3 represents H, and Rc4 represents Rc2 .

[0120] In some embodiments of the method for preparing the compound of Formula (I) of the present disclosure, the aminoalkylation reaction can be carried out, for example, in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at a temperature ranging from room temperature to 80°C (e.g., 40°C to 60°C, 40°C to 50°C, or 50°C to 60°C). In some embodiments, the molar ratio of the compound of formula (M1) to the compound of formula (M2) can be, for example, 1.0 to 2:1, 1:1.0 to 2, 1:1.1 to 2, 1:1.1 to 1.5, 1:1.1 to 1.2, or 1:1.2 to 1.3, etc.

[0121] In some embodiments of the method for preparing the compound of Formula (I) in the R» -^-N-N A! NH present disclosure, when -Rw1-Rw2 in the compound of Formula (M1) represents (Rdi)m or 4-r^Aijj-NH2 (Rdi)m , the compound of Formula (M1) is prepared by a reaction using the compound of Formula (M3) and the compound of Formula (M4) as starting materials, (M3) (Rdl)n1 (M4) Y represents F or Br; W1 represents H, and W2 represents an amino protecting group; or W1 represents an amino protecting group, and W2 represents H.

[0122] In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, when Y represents F, the compound of Formula (M3) and the compound of Formula (M4) undergo a palladium-catalyzed coupling reaction to prepare the compound of Formula (M1). In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, the palladium-catalyzed coupling reaction can be carried out in the presence of cesium carbonate, a palladium catalyst, and N,N-dimethylformamide at a temperature of, for example, 50 oC to 100 oC (e.g., 80 oC).

[0123] In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, when Y represents Br, the compound of Formula (M3) and the compound of Formula (M4) undergo a substitution reaction to prepare the compound of Formula (M1). In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, the substitution reaction can be carried out in the presence of N,N-diisopropylethylamine and dimethyl sulfoxide at a temperature of, for example, 80 oC to 150 oC (e.g., 130 oC).

[0124] In some embodiments of the method for preparing the compound of Formula (I) in the present disclosure, the amino protecting group can be, for example, Boc and the like. The deprotection of the protecting groups can be achieved by techniques and methods well known to those skilled in the art. For example, the removal of the Boc protecting group can be achieved under acidic conditions, such as hydrochloric acid or trifluoroacetic acid. VII. Definitions

[0125] Unless otherwise specified, the following words, phrases and symbols used herein generally have the meanings as described below.

[0126] In general, the nomenclature used herein (including the IUPAC nomenclature) and the laboratory procedures described below (including those used in cell culture, organic chemistry, analytical chemistry, and pharmacology, etc.) are those well-known and commonly used in the art. Unless otherwise defined, all scientific and technical terms used herein in connection with the present disclosure described herein have the same meaning as commonly understood by one skill in the art. In addition, the use of the word “a” or “an” when used in conjunction with the term “comprising” or a noun in the claims and / or the specification may mean “one”, but it is also consistent with the meaning of “one or more”, “at least one”, and “one or more than one”. Similarly, the terms "another" or "other" can mean at least a second or more.

[0127] It should be understood that whenever the term "comprise" or "include" is used herein to describe various aspects, other similar aspects described by "consisting of" and / or "consisting essentially of" are also provided.

[0128] As used herein, the term "about" used alone or in combination refers to approximately, roughly, nearly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the stated numerical value. In general, the term "about" can modify a numerical value above and below the stated value by an upward or downward (increasing or decreasing) variation, e.g., 10%, 5%, 2%, or 1%.

[0129] As used herein, the wording "...represents a bond" used alone or in combination means that the referenced group is a bond linker (that is, the referenced group is absent). For example, the wording "Rc represents a bond" means that Rc is a bond linker. In other words, when Rc represents a bond, the ring B in the structure of Formula (I) is directly connected to the ring A in the structure of Formula (I).

[0130] In this document, the term "optionally substituted with" used alone or in combination means that the referenced group may be unsubstituted or substituted with one or more substituents as defined here. Herein, the wording "optionally substituted with..." and "unsubstituted or substituted" can be used interchangeably. The term "substituted" generally represents the replacement of one or more hydrogen atoms in the referenced structure by identical or different specific substituents. The number of substituents is not theoretically limited in any way, or is automatically limited by the size of the building units (i.e., the total number of replaceable hydrogen atoms in the building units), or as clearly defined herein.

[0131] Herein, a bond interrupted by a wavy line shows the point of attachment of the depicted group to the rest of the molecule. For example, the monovalent group depicted below 4-Rc4(      c) (Rd2)n2 (Rd3)n3 shows the point of attachment of Rc in said group to R in the structure of Formula (I).

[0132] As used herein, the term "one or more" in the expression "substituted with one or more substituents selected from the group consisting of ...", whether used alone or in combination, means that some or allof the hydrogen atoms of the referenced group are replaced by a substituent or substituents. The number of substituents includes but is not limited to 1 to 40, such as 1 to 30, 1 to 25, 1 to 20, 1 to 15, 1 to 10, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1. The number of hydrogens to be replaced is in principle not limited in any way, or is automatically limited by the size of the building unit. For example, where the referenced group is a methyl group, the number of substituents may be 1 to 3.

[0133] As used herein, the term "deuterated" used alone or in combination, indicates that one or more hydrogen atoms in the referenced group are replaced by deuterium atoms.

[0134] As used herein, the term "oxo" or "oxo group" used alone or in combination, refers to = O.

[0135] As used herein, the term “C(O)” or “C(=O)” used alone or in combination, refers to a carbonyl group.

[0136] As used herein, the term "halogen atom" or "halogen", used alone or in combination, refers to fluorine, chlorine, bromine, or iodine.

[0137] As used herein, the term "alkyl", used alone or in combination, refers to a linear or branched alkyl group. The term "Cx-Cy alkyl" or "Cx-y alkyl" (x and y each being an integer) refers to a linear or branched alkyl group containing from x to y carbon atoms. The term "C1-10 alkyl" used alone or in combination in the present disclosure refers to a linear or branched alkyl group containing from 1 to 10 carbon atoms. Examples of the C1-10 alkyl of the present disclosure may include a C1-9 alkyl, C1-8 alkyl, C2-8 alkyl, C1-7 alkyl, C1-6 alkyl, C1-5 alkyl, C1-4 alkyl, C1-3 alkyl, and C1-2 alkyl. Representative examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl. The term "C1-3 alkyl" or "C1-C3 alkyl" in the present disclosure refers to an alkyl group containing from 1 to 3 carbon atoms, and representative examples thereof include methyl, ethyl, n-propyl, and isopropyl. In the present disclosure, the "alkyl" is optionally substituted, and the substituent(s) may be one or more (e.g., 110, 1-6, 1-5, 1-4, or 1-3) groups each independently selected from the group consisting of e.g., halogen, hydroxyl, cyano, C1-3 alkyl, C1-3 alkoxy, halogenated C1-6 alkoxy, halogenated C1-6 alkyl (e.g., trifluoromethyl), C3-6 cycloalkyl, 4- to 7-membered heterocyclyl, and combinations thereof.

[0138] As used herein, the term "halogenated alkyl", used alone or in combination, refers to a linear or branched alkyl group substituted with one or more halogens, wherein one or more hydrogen atom(s) of the alkyl group are replaced with one or more halogens. The term "halogenated Cx-Cy alkyl" or "halogenated Cx-y alkyl" (x and y are each an integer) refers to a linear or branched alkyl containing from x to y carbon atoms substituted with one or more halogens. The term "halogenated C1-10 alkyl" used alone or in combination in the present disclosure refers to a linear or branched alkyl group containing from 1 to 10 carbon atoms substituted with one or more halogens. Examples of the halogenated C1-10 alkyl group of the present disclosure include halogenated C1-9 alkyl group, e.g., halogenated C1-8 alkyl group, halogenated C2-8 alkyl group, halogenated C1-7 alkyl group, halogenated C1-6 alkyl, halogenated C1-5 alkyl, or halogenated C1-4 alkyl. Representative examples include halomethyl, haloethyl, halo-n-propyl, haloisopropyl, halo-n-butyl, haloisobutyl, halo-sec-butyl, halo-tert-butyl, halopentyl, haloisoamyl, haloneopentyl, halo-tert-pentyl, halohexyl, haloheptyl, halooctyl, halononyl, and halodecyl. The term "halogenated C1-3 alkyl" or "halogenated C1-C3 alkyl" of the present disclosure refers to an alkyl group containing from 1 to 3 carbon atoms substituted with one or more halogens, and its representative examples include halomethyl (e.g., trifluoromethyl), haloethyl, halo-n-propyl, and haloisopropyl.

[0139] As used herein, the term "deuterated alkyl", used alone or in combination, refers to a linear or branched alkyl group substituted with one or more deuterium atoms, wherein one or more hydrogen atoms of the alkyl group are replaced with one or more deuterium atoms. The term "deuterated Cx-Cy alkyl" or "deuterated Cx-y alkyl" (x and y are each an integer) refers to a linear or branched alkyl containing from x to y carbon atoms substituted with one or more deuterium atoms. The term "deuterated C1-10 alkyl" used alone or in combination in the present disclosure refers to a linear or branched alkyl group containing from 1 to 10 carbon atoms substituted with one or more deuterium atoms. Examples of the deuterated C1-10 alkyl group of the present disclosure include deuterated C1-9 alkyl group, e.g., deuterated C1-8 alkyl group, deuterated C2-8 alkyl group, deuterated C1-7 alkyl group, deuterated C1-6 alkyl, deuterated C1-5 alkyl, or deuterated C1-4 alkyl. Representative examples include perdeuterated methyl (CD3), perdeuterated ethyl (CD3CD2), perdeuterated n-propyl, perdeuterated isopropyl, perdeuterated n-butyl, perdeuterated isobutyl, perdeuterated sec-butyl, perdeuterated tert-butyl, perdeuterated pentyl, perdeuterated isopentyl, perdeuterated neopentyl, perdeuterated tert-pentyl, and perdeuterated hexyl. The term "deuterated C1-3 alkyl" or "deuterated C1-C3 alkyl" of the present disclosure refers to an alkyl group containing from 1 to 3 carbon atoms substituted with one or more deuterium atoms, and its representative examples include perdeuterated methyl (CD3) and perdeuterated ethyl (CD3CD2).

[0140] As used herein, the term "alkoxy", used alone or in combination, refers to a linear or branched alkoxy group having structural formula of alkyl-O-. Optionally, the alkyl portion of the alkoxy group may contain 1-10 (e.g., 1-6, 1-4, or 1-3) carbon atoms. Representative examples of "alkoxy" include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy, 2-pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, 2-hexyloxy, 3-hexyloxy, 3-methylpentyloxy, etc. The term "C1-C6 alkoxy" or "C1-6 alkoxy" refers to a linear or branched alkoxy group containing from 1 to 6 carbon atoms. Representative examples of C1-6 alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, butoxy, pentyloxy, and hexyloxy.

[0141] As used herein, the term "halogenated alkoxy", used alone or in combination, refers to an alkoxy group substituted with one or more halogen atoms. Optionally, the alkyl portion of the alkoxy group may contain 1-10 (e.g., 1-6, 1-4, or 1-3) carbon atoms. Examples of "halogenated alkoxy" include halogenated C1-6 alkoxy and halogenated C1-4 alkoxy. Representative examples include, but are not limited to, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-.

[0142] As used herein, the term "heteroaryl", used alone or in combination, refers to a 5- to 30membered (e.g., 5- to 20-membered, 5- to 15-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 6- to 15-membered, 6- to 9-membered, 6- to 10-membered, or 6- to 20-membered) monocyclic, bicyclic, or polycyclic cyclic hydrocarbon radical containing at least one aromatic ring having one or more (e.g., from 1 to 6, or from 1 to 5, or from 1 to 4, or from 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroaryl groups include bicyclic, tricyclic, tetracyclic, or polycyclic heteroaryl groups, which contain one aromatic ring having one or more (e.g., 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from O, S and N, and the remaining rings which may be a saturated, partially unsaturated or aromatic ring and can be carbocyclic ring or contain one or more (e.g., 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from O, S and N. Examples of monocyclic heteroaryl include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, tetrazolyl, and triazinyl. Examples of bicyclic heteroaryl include, but are not limited to, indolyl, isoindolyl, isoindolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, oxazolopyridyl, furopyridyl, pteridyl, purinyl, pyridopyridyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, chromanyl, and 6,7-dihydrothieno[3,2-d]pyrimidinyl. Examples of tricyclic or tetracyclic heteroaryl include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, xanthyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl. The heteroaryl group may be unsubstituted or substituted. A substituted heteroaryl refers to heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) by a substituent(s) optionally selected from the group consisting of e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0143] As used herein, the term "heteroarylene", used alone or in combination, refers to a 5- to 30membered (e.g., 5- to 20-membered, 5- to 15-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 6- to 15-membered, 6- to 9-membered, 6- to 10-membered, or 6- to 20-membered) bivalent monocyclic, bicyclic, or polycyclic cyclic hydrocarbon radical containing at least one aromatic ring having one or more (e.g., from 1 to 6, or from 1 to 5, or from 1 to 4, or from 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroarylene groups include bicyclic, tricyclic, tetracyclic or polycyclic heteroarylene groups, which contain one aromatic ring having one or more (e.g., 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from O, S and N, and the remaining ring(s) which may be a saturated, partially unsaturated or aromatic ring and can be carbocyclic ring or contain one or more (e.g., 14, 1-3, 1-2, or 1) heteroatoms independently selected from O, S and N. Examples of monocyclic heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, tetrazolylene, and triazinylene. Examples of bicyclic heteroarylene groups include, but are not limited to, indolylene, isoindolylene, isoindolinylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene,      benzothiazolylene,      benzisothiazolylene,      benzotriazolylene, benzo[2,1,3]oxadiazolylene,      benzo[2,1,3]thiadiazolylene,      benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, oxazolopyridylene, furopyridylene, pteridylene, purinylene, pyridopyridylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene, imidazo[2,1-b]thiazolylene, chromanylene, and 6,7-dihydrothieno[3,2-d]pyrimidinylene. Examples of tricyclic or polycyclic heteroarylene groups include, but are not limited to, acridinylene, benzindolylene, carbazolylene, dibenzofuranylene, xanthylene, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinylene,             and             6,7-dihydro-5H- cyclopenta[4,5]thieno[2,3-d]pyrimidinylene. The heteroarylene group may be unsubstituted or substituted. A substituted heteroarylene refers to heteroarylene substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) by a substituent(s) optionally selected from the group consisting of e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0144] As used herein, the term "aryl", used alone or in combination, refers to a monovalent aromatic hydrocarbon group containing from 5 to 30 (e.g., from 5 to 20, from 5 to 15, from 5 to 12, from 5 to 10, from 5 to 9, from 5 to 8, from 5 to 7, from 5 to 6, from 6 to 15, from 6 to 9, from 6 to 10, or from 6 to 20) carbon atoms and optionally one or more fused rings, such as phenyl group, naphthyl group, and fluorenyl group. As used herein, the "aryl" is optionally substituted. A substituted aryl group refers to an aryl group substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent(s). For example, aryl is mono-, di-, tri-, or poly-substituted with a substituent(s) optionally selected from e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0145] As used herein, the term "arylene", used alone or in combination, refers to a divalent aromatic hydrocarbon group containing from 5 to 30 (e.g., from 5 to 20, from 5 to 15, from 5 to 12, from 5 to 10, from 5 to 9, from 5 to 8, from 5 to 7, from 5 to 6, from 6 to 15, from 6 to 9, from 6 to 10, or from 6 to 20) carbon atoms and optionally one or more fused rings, such as phenylene (e.g., ’KD^,      , and ^V^), naphthylene, or fluorenylene. As used herein, the "arylene" is optionally substituted. A substituted arylene refers to an arylene group substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent(s). For example, arylene is mono-, di-, tri-, or poly-substituted with a substituent(s) optionally selected from e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0146] As used herein, the term "cycloalkyl", used alone or in combination, refers to a saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) monocyclic or bicyclic or tricyclic or polycyclic cyclic hydrocarbon radical, containing a number of carbon atoms including, but not limited to, from 3 to 30 carbon atoms (i.e., C3-30 cycloalkyl), or from 3 to 25 carbon atoms (i.e., C3-25 cycloalkyl), or from 3 to 20 carbon atoms (i.e., C3-20 cycloalkyl), or from 3 to 15 carbon atoms (i.e., C3-15 cycloalkyl), or from 3 to 12 carbon atoms (i.e., C3-12 cycloalkyl), or from 3 to 11 carbon atoms (i.e., C3-11 cycloalkyl), or from 3 to 10 carbon atoms (i.e., C3-10 cycloalkyl), or from 3 to 8 carbon atoms ( i.e., C3-8 cycloalkyl), or from 3 to 7 carbon atoms (i.e., C3-7 cycloalkyl), or from 3 to 6 carbon atoms (i.e., C3-6 cycloalkyl), or from 4 to 20 carbon atoms ( i.e., C4-20 cycloalkyl), or from 4 to 15 carbon atoms ( i.e., C4-15 cycloalkyl), or from 4 to 12 carbon atoms (i.e., C4-12 cycloalkyl), or from 4 to 10 carbon atoms (i.e., C4-10 cycloalkyl). The term "cycloalkyl" includes monocyclic, bicyclic, tricyclic, and polycyclic cyclic hydrocarbon radical having from 3 to 30 carbon atoms. Examples of the term "cycloalkyl" include, but are not limited to, monocyclic cycloalkyl, bridged cycloalkyl (e.g., C5-30 bridged cycloalkyl or C5-20 bridged cycloalkyl, C5-15 bridged cycloalkyl, and C7-15 bridged cycloalkyl), fused cycloalkyl (e.g., C5-30 fused cycloalkyl, C5-20 fused cycloalkyl, C5-15 fused cycloalkyl, C6-30 fused cycloalkyl, C6-20 fused cycloalkyl, C6-15 fused cycloalkyl, C7-30 fused cycloalkyl, C7-20 fused cycloalkyl, C7-15 fused cycloalkyl, and C8-15 fused cycloalkyl), and spirocycloalkyl (e.g., C5-30 spiro-cycloalkyl, C5-20 spiro-cycloalkyl, C5-15 spiro-cycloalkyl, C6-30 spirocycloalkyl, C6-20 spiro-cycloalkyl, C6-15 spiro-cycloalkyl, C7-30 spiro-cycloalkyl, C7-20 spirocycloalkyl, C7-15 spiro-cycloalkyl, and C8-15 spiro-cycloalkyl). Representative examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Examples of bridged cycloalkyl, fused cycloalkyl and spiro-cycloalkyl groups include, but are not limited to, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, C5-20 spiro-cycloalkyl, C5-15 spiro-cycloalkyl, adamantanyl, noradamantanyl, bornyl, and norbornyl (also named as bicyclo[2.2.1]heptyl by the IUPAC system). As used herein, the "cycloalkyl" is optionally mono- or poly-substituted, such as, but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl. The substituents of the substituted "cycloalkyl" can be optionally one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents independently selected from e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof. Examples of the term "C3-6 cycloalkyl" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, and cyclohexyl.

[0147] As used herein, the term "Cx-y spiro-cycloalkyl" (x and y each being an integer), used alone or in combination, refers to a spiro-cycloalkyl group containing from x to y carbon atoms. As used herein, the term "C5-30 spiro-cycloalkyl", used alone or in combination, refers to a spiro-cycloalkyl group containing from 5 to 30 carbon atoms (e.g., but not limited to, 5-20, 5-15, 7-20, 7-15, 5-11, 5-10, and 7-9 carbon atoms). The term "C5-30 spirocycloalkyl" includes "C5-20 spirocycloalkyl", "C5-15 spirocycloalkyl", "C7-15 spirocycloalkyl", and "C7-20 spirocycloalkyl", and representative examples of which include, but are not limited to, spiro[3.3]heptanyl, spiro[2.5]octanyl, spiro[3.5]nonanyl, spiro[3.5]nonenyl, spiro[4.4]nonanyl, spiro[4.5]decanyl, spiro[4.5]decenyl, and spiro[5.5]undecanyl. The "C5-30 spiro-cycloalkyl" is optionally further substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) substituents selected from the group consisting of e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0148] As used herein, the term "Cx-y bridged cycloalkyl" (where x and y are integers) used alone or in combination, refers to a bridged cycloalkyl group containing x to y carbon atoms. In the present invention, the term "C5-30 bridged cycloalkyl" used alone or in combination, refers to a bridged cycloalkyl group containing from 5 to 30 carbon atoms (e.g., but not limited to, 5-20, 620, 7-20, 5-15, 7-15, 5-11, 5-10, and 7-9 carbon atoms). The term "C5-30 bridged cycloalkyl" includes "C5-20 bridged cycloalkyl", "C6-20 bridged cycloalkyl", "C7-20 bridged cycloalkyl", "C5-15 bridged cycloalkyl", and "C7-15 bridged cycloalkyl", representative examples of which include, but are not limited to, adamantanyl, noradamantanyl, bornyl, norbornanyl (also named as bicyclo[2.2.1]heptanyl by the IUPAC system), 2-oxobicyclo[2.2.1]heptanyl, bicyclo[2.2.1]heptenyl, and cubanyl. Said "C5-30 bridged cycloalkyl" may be optionally substituted with 1 to 10 (e.g., 1-6, 1-5, 1-4, or 1-3) substituents selected from the group consisting of e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0149] As used herein, the term "cycloalkylene", used alone or in combination, refers to a saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) monocyclic, bicyclic, tricyclic or polycyclic divalent cyclic hydrocarbon radical, containing a number of carbon atoms including, but not limited to, from 3 to 30 carbon atoms (i.e., C3-30 cycloalkylene), or from 3 to 25 carbon atoms (i.e., C3-25 cycloalkylene), from 3 to 20 carbon atoms (i.e., C3-20 cycloalkylene), or from 3 to 15 carbon atoms (i.e., C3-15 cycloalkylene), or from 3 to 12 carbon atoms (i.e., C3-12 cycloalkylene), or from 3 to 11 carbon atoms (i.e., C3-11 cycloalkylene), or from 3 to 10 carbon atoms (i.e., C3-10 cycloalkylene), or from 3 to 8 carbon atoms ( i.e., C3-8 cycloalkylene), or from 3 to 7 carbon atoms (i.e., C3-7 cycloalkylene), or from 3 to 6 carbon atoms (i.e., C3-6 cycloalkylene), or from 4 to 20 carbon atoms (i.e., C4-20 cycloalkylene), or from 4 to 15 carbon atoms ( i.e., C4-15 cycloalkylene), or from 4 to 12 carbon atoms (i.e., C4-12 cycloalkylene), or from 4 to 10 carbon atoms (i.e., C4-10 cycloalkylene). The term "cycloalkylene" includes monocyclic, bicyclic, tricyclic and polycyclic divalent cyclic hydrocarbon radical having from 3 to 30 carbon atoms. Examples of the term "cycloalkylene" include, but are not limited to, monocyclic cycloalkylene, bridged cycloalkylene (e.g., C5-30 bridged cycloalkylene, C5-20 bridged cycloalkylene, C5-15 bridged cycloalkylene, and C7-15 bridged cycloalkylene), fused cycloalkylene (e.g., C5-30 fused cycloalkylene, C5-20 fused cycloalkylene, C5-15 fused cycloalkylene, C6-30 fused cycloalkylene, C6-20 fused cycloalkylene, C6-15 fused cycloalkylene, C7-30 fused cycloalkylene, C7-20 fused cycloalkylene, C7-15 fused cycloalkylene, and C8-15 fused cycloalkylene), and spiro-cycloalkylene (e.g., C5-30 spiro-cycloalkylene, C5-20 spirocycloalkylene, C5-15 spiro-cycloalkylene, C6-30 spiro-cycloalkylene, C6-20 spiro-cycloalkylene, C6-15 spiro-cycloalkylene, C7-30 spiro-cycloalkylene, C7-20 spiro-cycloalkylene, C7-15 spirocycloalkylene, and C8-15 spiro-cycloalkylene). Representative examples of monocyclic cycloalkylene groups include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, and cyclooctylene. Examples of bridged cycloalkylene, fused cycloalkylene and spiro-cycloalkylene groups include, but are not limited to, decalinylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C5-20 spiro-cycloalkylene (e.g., C5-15 spiro-cycloalkylene), adamantanylene, noradamantanylene, and norbornylene (also named as bicyclo[2.2.1]heptylene by the IUPAC system). As used herein, the "cycloalkylene" is optionally mono- or poly-substituted, such as, but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexylene. The substituents of the substituted "cycloalkylene" can be optionally one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents independently selected from the group consisting of e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0150] As used herein, the term "Cx-y spiro-cycloalkylene" (x and y each being an integer), used alone or in combination, refers to a spiro-cycloalkylene group containing from x to y carbon atoms. As used herein, the term "C5-30 spiro-cycloalkylene", used alone or in combination, refers to a spiro-cycloalkylene group containing from 5 to 30 carbon atoms (e.g., 5-20, 5-15, 7-20, 7-15, 511, 5-10, or 7-9 carbon atoms). The term "C5-30 spiro-cycloalkylene" includes "C5-20 spirocycloalkylene", "C5-15 spiro-cycloalkylene", "C7-15 spiro-cycloalkylene", and "C7-20 spirocycloalkylene", representative examples of which include, but are not limited to, spiro[3.3]heptylene,     spiro[2.5]octylene,     spiro[3.5]nonylene,     spiro[3.5]nonenylene, spiro[4.4]nonylene, spiro[4.5]decylene, spiro[4.5]decenylene, and spiro[5.5]undecylene. The "C5-30 spiro-cycloalkylene" is optionally further substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) substituents independently selected from the group consisting of e.g., deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0151] As used herein, the term "Cx-y bridged cycloalkylene" (where x and y are integers) used alone or in combination, refers to a bridged cycloalkylene group containing x to y carbon atoms. In the present invention, the term "C5-30 bridged cycloalkylene" used alone or in combination, refers to a bridged cycloalkylene group containing 5 to 30 (e.g., but not limited to, 5-20, 6-20, 720, 5-15, 7-15, 5-11, 5-10, and 7-9) carbon atoms. The term "C5-30 bridged cycloalkylene" includes "C5-20 bridged cycloalkylene", "C6-20 bridged cycloalkylene", "C7-20 bridged cycloalkylene", "C5-15 bridged cycloalkylene", and "C7-15 bridged cycloalkylene", representative examples of which include, but are not limited to, adamantanylene, noradamantanylene, bornylene, bicyclo[2.2.1]heptanylene, 2-oxobicyclo[2.2.1]heptanylene, bicyclo[2.2.1]heptenylene, and cubanylene. Said "C5-30 bridged cycloalkylene" may be optionally substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) substituents independently selected from the group consisting of deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0152] As used herein, the term "heterocyclyl" or "heterocyclic group", used alone or in combination, refers to a 4- to 30-membered (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 4- to 14-membered, 4- to 13-membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 4- to 5-membered, 5- to 9-membered, 5- to 30-membered, 5- to 20-membered, or 5- to 15-membered) saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) monocyclic, bicyclic, tricyclic or polycyclic cyclic hydrocarbon group containing one or more (e.g., from 1 to 5, or from 1 to 4, from 1 to 3, from 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the heterocyclyl group include, but not limited to, monocyclic heterocyclyl (e.g., 4- to 30membered monocyclic heterocyclyl, and 4- to 20-membered monocyclic heterocyclyl), bridged heterocyclyl (e.g., 5- to 30-membered bridged heterocyclyl, 5- to 20-membered bridged heterocyclyl, 7- to 20-membered bridged heterocyclyl, and 7- to 15-membered bridged heterocyclyl), fused heterocyclyl (e.g., 5- to 30-membered fused heterocyclyl, and 5- to 20membered fused heterocyclyl), and spiro-heterocyclyl groups (e.g., 5- to 30-membered spiro-heterocyclyl, and 5- to 20-membered spiro-heterocyclyl). Representative examples of the monocyclic heterocyclyl include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl), and diazacyclooctyl. Examples of bridged heterocyclyl, fused heterocyclyl and spiro-heterocyclyl groups include, but are not limited to, 6-azabicyclo[3.1.1]heptan-3-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-8-yl,       3,8-diazabicyclo[3.2.1]octan-8-yl,       3,8-diazabicyclo[3.2.1]octan-3-yl,       2,5- diazabicyclo[2.2.2]octan-2-yl, quinuclidinyl, octahydro-1H-indolyl, pyrrolidinocyclopropyl, cyclopentylaziridinyl, pyrrolidinocyclobutyl, pyrrolidinopyrrolidinyl (e.g., hexahydropyrrolo[3,4-c]pyrrolyl), pyrrolidinopiperidinyl, pyrrolidinopiperazinyl, pyrrolidinomorpholinyl, piperidinomorpholinyl, and azaspirocycloalkyl (e.g., 5- to 20-membered azaspirocycloalkyl, such as 3-azaspiro[5.5]undecan-3-yl and 7-azaspiro[3.5]nonyl). The heterocyclyl may be unsubstituted or substituted as explicitly defined (e.g., mono-, di-, tri-, or poly-substituted) by a substituent(s) optionally selected from the group consisting of deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0153] As used herein, the term "nitrogen-containing heterocyclyl", used alone or in combination, refers to 4- to 30-membered (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 4- to 14-membered, 4- to 13-membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 4- to 5-membered, 5- to 9-membered, 5- to 30-membered, 5- to 20-membered, or 5- to 15membered) saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) monocyclic, bicyclic, tricyclic or polycyclic cyclic hydrocarbon group containing one nitrogen atom and optionally one or more (e.g., from 1 to 5, or from 1 to 4, from 1 to 3, from 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the nitrogen-containing heterocyclyl group include, but are not limited to, nitrogen-containing monocyclic heterocyclyl (e.g., 4- to 30-membered nitrogen-containing monocyclic heterocyclyl, and 4- to 20-membered nitrogen-containing monocyclic heterocyclyl), nitrogen-containing bridged heterocyclyl (e.g., 5- to 30-membered nitrogen-containing bridged heterocyclyl, 5- to 20-membered nitrogen-containing bridged heterocyclyl, 5- to 15-membered nitrogen-containing bridged heterocyclyl, 7- to 20-membered nitrogen-containing bridged heterocyclyl, and 7- to 15-membered nitrogen-containing bridged heterocyclyl), nitrogencontaining fused heterocyclyl (e.g., 5- to 30-membered nitrogen-containing fused heterocyclyl, and 5- to 20-membered nitrogen-containing fused heterocyclyl), and nitrogen-containing spiro-heterocyclyl groups (e.g., 5- to 30-membered nitrogen-containing spiro-heterocyclyl, and 5- to 20membered nitrogen-containing spiro-heterocyclyl). Representative examples of the nitrogencontaining monocyclic heterocyclyl include, but are not limited to, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptan-1-yl), and diazacyclooctyl. Examples of nitrogen-containing bridged heterocyclyl, nitrogencontaining fused heterocyclyl and nitrogen-containing spiro-heterocyclyl groups include, but are not limited to, 6-azabicyclo[3.1.1]heptan-3-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl, quinuclidinyl, octahydro-1H-indolyl,     pyrrolidinocyclopropyl,      cyclopentylaziridinyl,     pyrrolidinocyclobutyl, pyrrolidinopyrrolidinyl (e.g., hexahydropyrrolo[3,4-c]pyrrolyl), pyrrolidinopiperidinyl, pyrrolidinopiperazinyl, pyrrolidinomorpholinyl, piperidinomorpholinyl, and azaspirocycloalkyl (e.g., 5- to 20-membered azaspirocycloalkyl, such as 3-azaspiro[5.5]undecan-3-yl and 7-azaspiro[3.5]nonyl). The nitrogen-containing heterocyclyl may be unsubstituted or substituted as explicitly defined (e.g., mono-, di-, tri-, or poly-substituted) by a substituent(s) optionally selected from the group consisting of deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0154] As used herein, the term "heterocyclylene", used alone or in combination, refers to a 4- to 30-membered saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) monocyclic, bicyclic, tricyclic or polycyclic bivalent cyclic hydrocarbon group containing one or more (e.g., from 1 to 5, or from 1 to 4, from 1 to 3, from 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the heterocyclylene groups include, but are not limited to, monocyclic heterocyclylene (e.g., 4-to 30-membered monocyclic heterocyclylene, and 4- to 20-membered monocyclic heterocyclylene), bridged heterocyclylene (e.g., 5- to 30-membered bridged heterocyclylene, 5- to 20-membered bridged heterocyclylene, 7- to 20-membered bridged heterocyclylene, and 7- to 15membered bridged heterocyclylene), fused heterocyclylene (e.g., 5- to 30-membered fused heterocyclylene, and 5- to 20-membered fused heterocyclylene), and spiro-heterocyclylene groups (e.g., 5- to 30-membered spiro-heterocyclylene, and 5- to 20-membered spiro-heterocyclylene). Representative examples of monocyclic heterocyclylene include, but are not limited to, azetidinylene,     oxetanylene,     pyrrolidinylene,     imidazolidylene,     pyrazolidylene, tetrahydrofuranylene, dihydropyranylene, tetrahydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azacyclooctylene, dioxacyclohexylene, diazacycloheptanylene (e.g., 1,4-diazacycloheptanylene, 4,5-diazacycloheptanylene, 1,3-diazacycloheptanylene), and diazacyclooctylene. Examples of the bridged heterocyclylene, fused heterocyclylene and spiro-heterocyclylene groups include, but are not limited to, 6-azabicyclo[3.1.1]heptanylene,             2,5-diazabicyclo[2.2.1]heptanylene,             3,6- diazabicyclo[3.1.1]heptanylene,               3-azabicyclo[3.2.1]octanylene,               3,8- diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, quinuclidinylene, octahydro-1H-indolylene, pyrrolidinocyclopropylene, cyclopentylaziridinylene, pyrrolidinocyclobutylene, pyrrolidinopyrrolidinylene (e.g., hexahydropyrrolo[3,4-c]pyrrolylene), pyrrolidinopiperidinylene, pyrrolidinopiperazinylene, pyrrolidinomorpholinylene, piperidinomorpholinylene, and azaspirocycloalkylene (e.g.,  5- to 20-membered azaspirocycloalkylene, such as 3- azaspiro[5.5]undecanylene and 7-azaspiro[3.5]nonylene). The heterocyclylene may be unsubstituted or substituted as explicitly defined (e.g., mono-, di-, tri-, or poly-substituted) by a substituent(s) optionally selected from the group consisting of deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0155] As used herein, the term "nitrogen-containing heterocyclylene", used alone or in combination, refers to a 4- to 30-membered (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 4- to 14-membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 4- to 5-membered, 5- to 9-membered, 5- to 30-membered, 5- to 20-membered, or 5- to 15membered) saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) monocyclic, bicyclic, tricyclic or polycyclic bivalent cyclic hydrocarbon group containing one nitrogen atom and optionally one or more (e.g., from 1 to 5, or from 1 to 4, from 1 to 3, from 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the nitrogen-containing heterocyclylene group include, but are not limited to, nitrogen-containing monocyclic heterocyclylene (e.g., 4- to 30-membered nitrogencontaining monocyclic heterocyclylene, and 4- to 20-membered nitrogen-containing monocyclic heterocyclylene), nitrogen-containing bridged heterocyclylene (e.g., 5- to 30-membered nitrogencontaining bridged heterocyclylene, 5- to 20-membered nitrogen-containing bridged heterocyclylene, 7- to 20-membered nitrogen-containing bridged heterocyclylene, and 7- to 15membered nitrogen-containing bridged heterocyclylene), nitrogen-containing fused heterocyclylene (e.g., 5- to 30-membered nitrogen-containing fused heterocyclylene, and 5- to 20membered nitrogen-containing fused heterocyclylene), and nitrogen-containing spiro-heterocyclylene (e.g., 5- to 30-membered nitrogen-containing spiro-heterocyclylene, and 5- to 20membered nitrogen-containing spiro-heterocyclylene). Representative examples of the nitrogencontaining monocyclic heterocyclylene include, but are not limited to, azetidinylene, pyrrolidinylene, imidazolidylene, pyrazolidylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azacyclooctylene, diazacycloheptanylene (e.g.,     1,4-diazacycloheptanylene, 4,5- diazacycloheptanylene, 1,3-diazacycloheptanylene), and diazacyclooctylene. Examples of nitrogen-containing bridged heterocyclylene, nitrogen-containing fused heterocyclylene, and nitrogen-containing spiro-heterocyclylene groups include, but are not limited to, 6-azabicyclo[3.1.1]heptanylene,             2,5-diazabicyclo[2.2.1]heptanylene,             3,6- diazabicyclo[3.1.1]heptanylene,               3-azabicyclo[3.2.1]octanylene,               3,8- diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, quinuclidinylene, octahydro-1H-indolylene, pyrrolidinocyclopropylene, cyclopentylaziridinylene, pyrrolidinocyclobutylene, pyrrolidinopyrrolidinylene (e.g., hexahydropyrrolo[3,4-c]pyrrolylene), pyrrolidinopiperidinylene, pyrrolidinopiperazinylene, pyrrolidinomorpholinylene, piperidinomorpholinylene, and azaspirocycloalkylene (e.g.,  5- to 20-membered azaspirocycloalkylene, such as 3- azaspiro[5.5]undecanylene and 7-azaspiro[3.5]nonanylene). The nitrogen-containing heterocyclylene may be unsubstituted or substituted as explicitly defined (e.g., mono-, di-, tri-, or poly-substituted) by a substituent(s) optionally selected from the group consisting of deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, and any combination thereof.

[0156] As used herein, the term "monoazabridged-cycloalkylene", used alone or in combination, refers to 5- to 30-membered (e.g., 5- to 30-membered, 5- to 25-membered, 5- to 20-membered, 5-to 15-membered, 5- to 14-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered) saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) bicyclic, tricyclic or polycyclic bivalent bridged cyclic hydrocarbon group containing one nitrogen atom. Examples of the   “monoazabridged-cycloalkylene”   include, but are not limited to, 6- azabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, and quinuclidinylene. The "monoazabridged-cycloalkylene" may be unsubstituted or substituted as explicitly defined (e.g., substituted with one or more substituents), wherein the substituents may be selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, or any combination thereof. The number of substituents is in principle not limited in any way, or is automatically limited by the size of the building unit. For example, the number of substituents may be one or more, such as 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1. refers to 5- to 30-membered (e.g., 5- to 30-membered, 5- to 25-membered, 5- to 20-membered, 5-to 15-membered, 5- to 14-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered) saturated or partially unsaturated (i.e., containing one or more double bonds, but not having a fully conjugated n-electron system) bicyclic, tricyclic or polycyclic bivalent spirocycloalkyl group containing one nitrogen atom. Examples of the “monoazaspirocycloalkylene” include, but are not limited to, 3-azaspiro[5.5]undecanylene and 7-azaspiro[3.5]nonanylene. The "monoazaspirocycloalkylene" may be unsubstituted or substituted as explicitly defined (e.g., substituted with one or more substituents), wherein the substituents may be selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 alkyl, halogenated C1-6 alkyl, optionally deuterated C3-6 cycloalkyl, optionally deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, optionally deuterated C1-6 alkyl-NH-, NH2-C1-6 alkylene, optionally deuterated C1-6 alkyl-NHC(O)-, optionally deuterated C1-6 alkyl-C(O)NH-, C2-6 alkynyl, C2-6 alkenyl, or any combination thereof. The number of substituents is in principle not limited in any way, or is automatically limited by the size of the building unit. For example, the number of substituents may be one or more, such as 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1.

[0158] As used herein, the term "alkynyl", used alone or in combination, refers to a linear or branched monovalent hydrocarbon group containing from 2 to 8 (e.g., from 2 to 6, from 2 to 5, from 2 to 4, or preferably 2) carbon atoms and having one or more (e.g., from 1 to 3, from 1 to 2, or 1) carbon-carbon triple bonds. Examples of alkynyl include C2-8 alkynyl, C2-6 alkynyl or C2-4 alkynyl, representative examples of which include, but are not limited to, ethynyl, 1-propynyl, 1-butynyl, and 1,3-diynyl.

[0159] As used herein, the term "alkenyl", used alone or in combination, refers to a linear or branched monovalent hydrocarbon group containing from 2 to 8 (e.g., from 2 to 6, from 2 to 5, from 2 to 4, from 2 to 3, or 2) carbon atoms and having one or more (e.g., from 1 to 3, from 1 to 2, or 1) carbon-carbon double bonds. Examples of alkenyl group include C2-8 alkenyl, C2-6 alkenyl or C2-4 alkenyl, representative examples of which include, but are not limited to, vinyl (e.g., CH2=CH-), 1-propenyl, allyl, 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl, pentenyl, n-pent-2,4-dienyl, 1-methyl-but-1-enyl, 2-methyl-but-1-enyl, 3-methyl-but-1-enyl, 1-methyl-but-2-enyl, 2-methyl-but-2-enyl, 3-methyl-but-2-enyl, 1-methyl-but-3-enyl, 2-methyl-but-3-enyl, 3-methyl-but-3-enyl, and hexenyl. trimethylbicyclo[2.2.1]heptane; camphane) has a definition known to those skilled in the art. As used herein, "camphanyl" or "bornyl" refers to a monovalent group of bornane, i.e., the group remaining after removal of any one hydrogen atom from bornane. Representative examples of "bornyl" include, but are not limited to, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-3-yl,       1,7,7-trimethylbicyclo[2.2.1]heptan-4-yl,       1,7,7- trimethylbicyclo[2.2.1]heptan-5-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-6-yl, v     , and .

[0161] As used herein, "bicyclo[2.2.1]heptane" also known as "norbornane", has a definition known to those skilled in the art. As used herein, "bicyclo[2.2.1]heptyl" or "norbornyl" refers to a monovalent group of bicyclo[2.2.1]heptane, i.e., the group remaining after removal of any one hydrogen atom from bicyclo[2.2.1]heptane. Representative examples of “bicyclo[2.2.1]heptyl” include, but are not limited to, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]heptan-3-yl, bicyclo[2.2.1]heptan-4-yl, bicyclo[2.2.1]heptan-5-yl, and bicyclo[2.2.1]heptan-6-yl.

[0162] As used herein, the term "bicyclo[2.2.1]heptene" has a definition known to those skilled in the art. As used herein, "bicyclo[2.2.1]heptenyl" refers to a monovalent group of bicyclo[2.2.1]heptene, i.e., the group remaining after removal of any one hydrogen atom from bicyclo[2.2.1]heptene. Representative examples of “bicyclo[2.2.1]heptenyl” include, but are not limited to, bicyclo[2.2.1]hept-5-en-2-yl, bicyclo[2.2.1]hept-5-en- 3-yl, or bicyclo[2.2.1]hept-5-en-7-yl.

[0163] As used herein, "adamantane" (also known as tricyclo[3.3.1.13,7]decane) has a definition known to those skilled in the art, and its structural formula is e.g., as follows:       . As used herein, "adamantanyl" refers to a monovalent group of adamantane, that is, the group remaining after removal of any one hydrogen atom from adamantane. Representative examples of “adamantanyl” include, but are not limited to, 1-adamantanyl, 2-adamantanyl, 3-adamantanyl, 4-adamantanyl, 5-adamantanyl, 6-adamantanyl, 7-adamantanyl, 8-adamantanyl, 9-adamantanyl, or 10-adamantanyl.

[0164] As used herein, the term "noradamantane" (also known as octahydro-2,5-methanopentalene) has the definition known to those skilled in the art, and its structural formula is, for example, as shown below:       or      . As used herein, "noradamantanyl" refers to a monovalent group derived from noradamantane, i.e., the group remaining after removal of any one hydrogen atom from noradamantane. Representative examples of "noradamantanyl" include, but are not limited to, 1-noradamantanyl, 2-noradamantanyl, 3-noradamantanyl, 4-noradamantanyl, 5-noradamantanyl, 6-noradamantanyl, 7-noradamantanyl, 8-noradamantanyl, and 9-noradamantanyl.

[0165] As used herein, "adamantanamine" has the definitions known to those skilled in the art, namely referring to an adamantane having an amino substituent, wherein the amino substituent can replace a hydrogen on a carbon at any position in the adamantane. An example of "adamantanamine" can be adamantan-1-amine (the corresponding English chemical name is adamantan-1-amine or Tricyclo[3.3.1.13,7]decan-1-amine; CAS No.: 768-94-5), with the following structural formula:

[0166] Salts or pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates, prodrugs, polymorphs of the compounds of the present disclosure (including compounds of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) are also encompassed within the scope of the present disclosure.

[0167] In all embodiments of the present disclosure, the salts or pharmaceutically acceptable salts of the compounds of Formula (I) (including compounds of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (II-1), Formula (II-2), Formula (II-3), Formula (II-4), or Formula (I’)) refer to non-toxic inorganic or organic acid and / or base addition salts. Examples include: sulfates, hydrohalides (including hydrochlorides, hydrobromides), citrates, maleates, lactates, lactobionates, L-tartrates, fumarates, L-malates, L-lactates, a-Ketoglutarates, hippurates, D-glucuronates, D-gluconates, a-D-glucoheptonates, glycolates, mucates, L-ascorbates, orotates, picrates, glycinates, alaninates, argininates, cinnamates, laurates, pamoates, sebacates, benzenesulfonates, methanesulfonates, ethanesulfonates, edisylates, formates, acetates, 2,2-dichloroacetates, trimethylacetates, propionates, valerates, palmitates, triphenylacetates, 2-ethylsuccinates, iodates, niacinates, L-pyroglutamates, L-prolinates, ferulates, 2-hydroxyethanesulfonates, nitrates, gentisates, cholates, salicylates, terephthalates, glutarates, adipates, stearates, oleates, undecenoates, camphorates, camphorsulfonates, dodecyl sulfonates, phosphates, thiocyanates, dihydrophosphates, pyrophosphates, metaphosphates, oxalates, carbonates, malonates, benzoates, mandelates, succinates, pyruvates, parachlorobenzenesulfonates, 1,5-naphthalenedisulfonates, 3-hydroxy-2-naphthoates, 1-hydroxy-2-naphthoates, 2-naphthalenesulfonates, glycolate, trifluoroacetate, terephthalate, and 4-methylbenzenesulfonate, etc.

[0168] "Pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, such as a filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickener, solvent, or encapsulating material, with which the useful compounds according to the present disclosure are carried or transported into or administered to a patient so that they can perform their intended function. Generally, such constructs are carried or transported from one organ or part of the body to another organ or part of the body. The carrier is compatible with the other ingredients of the formulation, including the compounds useful in the present disclosure, and is not harmful to the patient, and the carrier must be "acceptable". Some examples of materials that can be used as pharmaceutically acceptable carriers include sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository wax; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; surfactant phosphate buffer solution; and other common non-toxic compatible substances used in pharmaceutical formulations.

[0169] As used herein, the term "room temperature" refers to the ambient temperature, such as 20-30C.

[0170] As used herein, "stereoisomer" refers to a compound with the same chemical structural formula, but a different arrangement of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotational isomers), geometric isomers (cis / trans isomers), atropisomers, and so on.

[0171] As used herein, the term "solvate" refers to an association or complex formed by the interaction between one or more solvent molecules and the compounds of the present invention. Examples of solvents include water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid and ethanolamine. The term "hydrate" means that a complex formed with water. mirror image; whereas "achiral" refers to a molecule that can be superimposed on its mirror image.

[0173] As used herein, the term "enantiomers" refers to two isomers of a compound that are non-superimposable mirror images.

[0174] As used herein, the term "diastereomers" refers to stereoisomers that have two or more chiral centers but are not mirror images of each other. The diastereomers have different physical properties, such as melting point, boiling point, spectral properties and reactivity. The diastereomeric mixture can be separated by high-resolution analytical operations such as electrophoresis and chromatography, such as HPLC.

[0175] As used herein, the term "prodrug" refers to a compound that can be converted in vivo, such as by hydrolysis in the blood, into its biologically active form. When a prodrug is administered to a patient, it releases the parent compound in the body. Prodrugs are generally prepared by modifying functional groups, and such modifications can be removed by conventional operations (e.g., acid / base hydrolysis) or by cleavage in vivo to release the parent drug. Prodrugs include, for example, forms in which the hydroxyl, amino, or mercapto groups of the compounds of the present invention are combined with any group that, when administered to a patient, can be cleaved to re-form the hydroxyl, amino, or mercapto groups. Accordingly, representative examples of prodrugs include, but are not limited to, acetate / amide, formate / amide, tert-butoxycarbonyl (Boc), and benzoate / amide derivatives of the hydroxyl, mercapto, and amino functional groups of the compounds of Formula (I) and Formula (II). In addition, in the case of carboxylic acids (-COOH), esters such as methyl esters, ethyl esters, and the like can be used. These esters may themselves be active and / or may be hydrolyzed under physiological conditions in the human body. Suitable pharmaceutically acceptable, in vivo hydrolyzable ester groups include those that are readily cleaved in the human body to release the parent acid or a salt thereof.

[0176] As used herein, "p-menthane" has the definitions known to those skilled in the art, and its structural formula is e.g., as follows:          . As used herein, "p-menthanyl" refers to a monovalent group of p-menthane, that is, the group remaining after removal of any one hydrogen atom from p-menthane. Representative examples of “p-menthanyl” include, but are not limited to, and

[0177] As used herein, "m-menthane" has the definitions known to those skilled in the art, and its structural formula is e.g., as follows: /      . As used herein, "m-menthanyl" refers to a monovalent group of m-menthane, that is, the group remaining after removal of any one hydrogen atom from m-menthane. Representative examples of “m-menthanyl” include, but are not limited to, , and

[0178] As used herein, "Quinuclidine" (also known as 1-azabicyclo[2.2.2]octane) has the definitions known to those skilled in the art, and its structural formula is e.g., as follows:      . As used herein, "quinuclidinyl" refers to a monovalent group of Quinuclidine, that is, the group remaining after any hydrogen in Quinuclidine is removed. Representative examples of “quinuclidinyl” include, but are not limited to, N , and Description of the Drawings

[0179] FIG. 1 shows the Western Blot results of target substrate protein degradation induced by the compounds of the present invention in hPBMCs. Examples

[0180] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure. The present disclosure may be practiced without some or all of these specific details. In other cases, well-known process operations have not been described in detail in order not to unnecessarily obscure the present disclosure. Although the present disclosure will be described in conjunction with specific embodiments, it should be understood that this is not intended to limit the present disclosure to these embodiments.

[0181] The following abbreviations are used throughout the specification and examples: AcOH            acetic acid Boc               t-Butyloxy carbonyl DCM            dichloromethane 92 DIEA or DIPEA N, N-diisopropylethylamine DMF N,N-dimethylformamide DMSO dimethyl sulfoxide EA ethyl acetate ESI electrospray ionization equiv equivalent EtOH ethanol EtOAc ethyl acetate HPLC high performance liquid chromatography HRMS high resolution mass spectrometry LC-MS liquid chromatography-mass spectrometry LRMS low resolution mass spectrometry LC liquid chromatography Me methyl MeCN acetonitrile MeOH methanol MS mass spectrometry MsCl methanesulfonyl chloride MsO- methanesulfonyloxy Ms2O 1H NMR methanesulfonic anhydride Proton nuclear magnetic resonance MeO- methoxy ONs o-nitrobenzenesulfonyl rt room temperature tBu tert-butyl TEA triethylamine TFA trifluoroacetic acid TfO- trifluoromethanesulfonate TLC thin layer chromatography TMS tetramethylsilane TsO- tosyloxy Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene X-Phos 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

[0182] In the present disclosure, the 1H NMR spectrum was recorded on a Bruker-500MHz nuclear magnetic resonance instrument, by using, as a solvent, CD3OD (8 = 3.31 ppm) containing 0.1% TMS (as an internal standard); or using, as a solvent, CDCI3 (8 = 7.26 ppm) containing 0.1% TMS (as an internal standard); or using, as a solvent, DMSO-d6 (8 = 2.50 ppm) containing 0.03% TMS (as an internal standard). LC-MS spectra were recorded on a Sciex API 2000 mass spectrometer equipped with an Agilent 1100 binary pump, DAD and ELSD detectors, or on an Agilent 12606125B single quadrupole LC-MS system equipped with an Agilent 1260 quaternary pump, DAD and ELSD detectors. HPLC preparative purification was performed using a SHIMADZU LC-20AP system. HPLC purity was determined using either a SHIMADZU LC-30AP or Waters 1525 system. Supercritical fluid chromatography (SFC) chiral resolution / separation was performed on a SHIMADZU LC-20AP instrument equipped with a Daicel CHIRALPAK®IE column. All reactions were carried out under ambient atmosphere unless otherwise specified. Reaction progress was monitored by TLC or LC-MS.

[0183] Solvents and reagents are processed as follows: DCM, DMF, anhydrous EtOH, and anhydrous MeOH used in the reactions were purchased from Sinopharm Group; preparative-grade CH3CN and deionized water were used for HPLC preparation. Unless otherwise specified, all other raw materials, reagents, and chemicals were commercially available or could be synthesized according to methods known in the art.

[0184] The materials and reagents used in the following examples, unless otherwise specified, were either commercially available and used directly, or could be synthesized using or according to methods known in the art.

[0185] General synthesis methods

[0186] Compounds and / or pharmaceutically acceptable salts thereof of the present disclosure can be synthesized using commercially available raw materials by synthetic techniques known in the art. The synthetic schemes described below illustrate the preparation of most compounds. The starting materials or reagents used in each scheme can be purchased from commercial sources or prepared by methods known to those skilled in the art. One skilled in the art can prepare the salts, racemates, enantiomers, phosphates, sulfates, hydrochlorides and prodrug forms of the compounds of Formula (I) of the present disclosure according to routine techniques in the art.

[0187] Synthesis Scheme 1: Scheme 1 (Rd2)n2 (Rd3)n3

[0188] In Scheme 1, Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, ring B, (Rd2)n2, m1, ring C, and (Rd3)n3 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub embodiments thereof. In Scheme 1, (i) RLai and RLa3 represent N(Rw), RLa2 represents (Rdi)m , RLa4 represents    (Rdi)m , wherein Rw, ring A1, and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof; or (ii) RLa1 and RLa3 represent (Rdi)m , RTa2 represents -NH2, RLa4 represents NH or -N=; or (iii) RLa1 and RLa3 represents NH, RLa2 represents -NH2, RLa4 represents NH or -N=; or (^d4)n4 4-+ a2 n-nh2 (iv) RLa2 represents            , wherein ring A2 and (Rd4)n4 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof, ^3^^¾ ** RLa1 and RLa3 represent       0-2  , symbol ** indicates the point of attachment to ring (Rd4)n4 A2 , and RLa4 represents

[0189] The reductive amination reaction in Scheme 1 can be carried out using conventional techniques and methods well known to those skilled in the art. For example, the reductive amination reaction can be conducted in the presence of sodium triacetoxyborohydride and N,N-dimethylformamide, or sodium cyanoborohydride and 1,2-dichloroethane, at a temperature ranging from room temperature to 80 oC (e.g., room temperature to 50 oC, 40 oC to 60 oC, 40 oC to 50 oC, or 50 oC to 60 oC). The molar ratio of substrate 1-1 to substrate 1-2 can be, for example, 1:1.1 to 3, 1:1.1 to 2, 1:1.1 to 1.5, 1:1.1 to 1.2, or 1:1.2 to 1.3, etc.

[0190] For example, the procedure of Scheme 1 can be as follows:

[0191] To a solution of substrate 1-1 (1.0 eq.) and aldehyde substrate 1-2 (2.0 eq.) in N,N- dimethylformamide was added AcOH (1 drop). The reaction mixture was stirred at 50 oC for 2 hours and then cooled to room temperature. To the reaction mixture was then added sodium triacetoxyborohydride (4.0 eq.), and the mixture was stirred for an additional 17 hours. After the completion of the reaction was confirmed by LC-MS, the reaction mixture was filtered, and the filtrate was purified by high-performance liquid chromatography (HPLC) to afford the target compound.

[0192] Synthesis Scheme 2: Scheme 2

[0193] In Scheme 2, Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, Rc2, ring B, (Rd2)n2, m1, ring C, and (Rd3)n3 are as defined in the compounds of Formula (I) of the present disclosure and the respective subembodiments thereof. The group LE represents Cl, Br, I, OMs, OTs, or ONs. In Scheme 2, A! NH (i) RLbi and RLb3 represent NH, RLb2 represents (Rdi)m , and RLb4 represents (^d1 )n1 wherein ring A1 and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof; or (ii) RLb1 and RLb3 represent NH, RLb2 represents -NH2, and RLb4 represents NH; or (iii) RLbi and RLb3 represent    <R<n)m , RLb2 represents -NH2, and RLb4 represents NH, wherein ring A1 and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof; or (^d4)n4 a2 n-nh2 (iv) RLb2 represents            , wherein ring A2 and (Rd4)n4 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof, RLbi and RLb3 represent       0-2  , symbol ** indicates the point of attachment to ring (Rd4)n4 4-4a4—N-|- A2, and RLb4 represents              .

[0194] The aminoalkylation reaction in Scheme 2 can be carried out, for example, in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at a temperature ranging from room temperature to 80 oC (e.g., 40 oC to 60 oC, 40 oC to 50 oC, or 50 oC to 60 oC). The molar ratio of substrate 2-1 to substrate 2-2 can be, for example, 1:1.1 to 2, 1:1.1 to 1.5, 1:1.1 to 1.2, or 1:1.2 to 1.3, etc.

[0195] For example, the procedure of Scheme 2 can be as follows:

[0196] To a solution of substrate 2-1  (1.0 eq.) and substrate 2-2 (1.2 eq.) in N,N- dimethylformamide were added triethylamine (3.0 eq.) and sodium iodide (1.0 eq.), and the reaction mixture was stirred at room temperature for 18 hours. After the completion of the reaction was confirmed by LC-MS, the reaction mixture was filtered, and the filtrate was purified by HPLC to afford the target compound.

[0197] Synthesis Scheme 3: Scheme 3

[0198] In Scheme 3, Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, ring B, (Rd2)n2, m1, ring C, and (Rd3)n3 are as defined in the compounds of Formula (I) of the present disclosure and the respective subembodiments thereof. In Scheme 3, (i) Rlci and Rlc3 represent NH, Rlc2 represents (Rdi)m , and Rlc4 represents          , wherein ring A1 and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof; or (ii) RLc1 and RLc3 represent NH, RLc2 represents -NH2, and RLc4 represents NH; or (iii) Rlci and Rlc3 represent          , Rlc2 represents -NH2, and Rlc4 represents NH; or (^d4)n4 4-(- a2 n-nh2 (iv) Rlc2 represents            , wherein ring A2 and (Rd4)n4 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof, ** Rlci and Rlc3 represent       0-2  , symbol ** indicates the point of attachment to ring (^d4)n4 5              H . TT a2 n—n-^- A2, and Rlc4 represents '   '      .

[0199] For example, the procedure of Scheme 3 can be as follows:

[0200] To a solution of substrate 3-1  (1.0 eq.) and substrate 3-2 (1.2 eq.) in N,N- dimethylformamide were added HATU (1.5 eq.) and triethylamine (3.0 eq.), and the reaction mixture was stirred at room temperature for 18 hours. After the completion of the reaction was confirmed by LC-MS, the reaction mixture was filtered, and the filtrate was purified by HPLC to afford the target compound.

[0201] Synthesis Scheme 4: Urea Formation (Triphosgene) O O      (Ka5)m (Rd1)m 4-1 Scheme 4

[0202] In Scheme 4, Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, Rw, ring A1, (Rd1)n1, (Rd2)n2, m1, ring C, and (Rd3)n3 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof. Ring B represents nitrogen-containing heterocyclyl.

[0203] The procedure of Scheme 4 can be as follows:

[0204] To a solution of substrate 4-2 (1.0 eq.) and triphosgene (0.5 eq.) in dichloromethane was added triethylamine (3.0 eq.), and the reaction mixture was stirred at room temperature for 0.5 hours. A solution of substrate 4-1 in DMF was then added, and the resulting mixture was stirred for an additional 17 hours. After the completion of the reaction was confirmed by LC-MS, the reaction mixture was filtered, and the filtrate was purified by HPLC to give the target compound.

[0205] Synthesis Scheme 5: 5-1 palladium-catalyzed coupling reaction Scheme 5

[0206] In Scheme 5, Z, Ra1, Ra2, Ra3, Ra4, and (Ra5)m are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof.

[0207] The palladium-catalyzed coupling reaction in Scheme 5 can be carried out by conventional techniques and methods well known to those skilled in the art.

[0208] General procedure for Scheme 5: to a solution of halide substrate 5-1 (1.0 eq.) and amine substrate 5-2 (1.2 eq.) in N,N-dimethylformamide were added palladium catalyst (0.2 eq.) and cesium carbonate (3.0 eq.). The reaction flask was purged with nitrogen three times, and the reaction mixture was stirred at 80oC for 18 hours. After the completion of the reaction was confirmed by LC-MS, the reaction mixture was filtered, and the filtrate was purified by HPLC (eluent (v / v): acetonitrile / 0.05% aq. HCl = 5%-90%) to afford the target compound.

[0209] Synthesis Scheme A1: 0  0       (°a5)m A-1 A-1-1 A-1-2 A-1-3 Scheme A1

[0210] In Scheme A1, Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, Rw, ring A1, and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof.

[0211] The palladium-catalyzed coupling reaction and deprotection in Scheme A1 can be carried out by conventional techniques and methods well known to those skilled in the art.

[0212] The procedure of Scheme A1 can be as follows:

[0213] Step 1: At room temperature, to a 100 mL round-bottom flask were sequentially added compound A-1 (1.0 eq.), compound A-1-1 (1.2 eq.), cesium carbonate (2.0 eq.), palladium catalyst (0.025 eq.), and N,N-dimethylformamide. Under a nitrogen atmosphere, the reaction mixture was heated to 80 oC and stirred for 16 hours. After the completion of the reaction was confirmed by TLC, the reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate three times. The organic phases were combined. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford compound A-1-2 (gray solid, yield 73%).

[0214] Step 2: At room temperature, to a solution of compound A-1-2 in dichloromethane in a 100 mL round-bottom flask was added trifluoroacetic acid, and the reaction mixture was stirred for 1 hour. After the completion of the reaction was confirmed by TLC, the reaction mixture was concentrated under reduced pressure, and the resulting residue was lyophilized to afford compound A-1-3.

[0215] Synthesis Scheme A2: (Rd1 )n1 palladium-catalyzed coupling reaction A-2-2 A-2-3 A-1                         A-2-1 Scheme A2

[0216] In Scheme A2, Z, Ra1, Ra2, Ra3, Ra4, (Ra5)m, Rw, ring A1, and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof.

[0217] The palladium-catalyzed coupling reaction and deprotection in Scheme A2 can be carried out by conventional techniques and methods well known to those skilled in the art.

[0218] The procedure of Scheme A2 can be as follows:

[0219] Step 1: At room temperature, to a 100 mL round-bottom flask were sequentially added compound A-1 (1.0 eq.), compound A-2-1 (1.2 eq.), cesium carbonate (2.0 eq.), palladium catalyst (0.025 eq.), and N,N-dimethylformamide. Under a nitrogen atmosphere, the reaction mixture was heated to 80 oC and stirred for 16 hours. After the completion of the reaction was confirmed by TLC, the reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate three times. The organic phases were combined. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford compound A-2-2 (gray solid, yield 73%).

[0220] Step 2: At room temperature, to a solution of compound A-2-2 in dichloromethane in a 100 mL round-bottom flask was added trifluoroacetic acid, and the reaction mixture was stirred for 1 hour. After the completion of the reaction was confirmed by TLC, the reaction mixture was concentrated under reduced pressure, and the resulting residue was lyophilized to afford compound A-2-3.

[0221] Synthesis Scheme B1: B-1 (Rdl)n1 B-1-1 substitution reaction B-1-2 B-1-3 Scheme B1

[0222] In Scheme B1, Ra1, Ra2, Ra3, Ra4, Rw, ring A1, and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof. X represents H or F.

[0223] The substitution reaction and deprotection in Scheme B1 can be carried out by conventional techniques and methods well known to those skilled in the art.

[0224] The procedure of Scheme B1 can be as follows:

[0225] Step 1: At room temperature, to a 100 mL round-bottom flask were sequentially added compound B-1 (1.0 eq.), compound B-1-1 (1.2 eq.), N,N-diisopropylethylamine (5.0 eq.), and dimethyl sulfoxide. Under a nitrogen atmosphere, the reaction mixture was heated to 130 °C and stirred for 16 hours. After the completion of the reaction was confirmed by TLC, the reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate three times. The organic phases were combined. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford compound B-1-2 (gray solid, yield 62%).

[0226] Step 2: At room temperature, to a solution of compound B-1-2 in dichloromethane in a 100 mL round-bottom flask was added trifluoroacetic acid, and the reaction mixture was stirred for 1 hour. After the completion of the reaction was confirmed by TLC, the reaction mixture was concentrated under reduced pressure, and the resulting residue was lyophilized to afford compound B-1-3.

[0227] Synthesis Scheme B2: Rw I HN A, N-N_ V1V Boc (Rd1 )n1 B-2-1 substitution reaction B-2-3 Scheme B2

[0228] In Scheme B2, Ra1, Ra2, Ra3, Ra4, Rw, ring A1, and (Rd1)n1 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof. X represents H or F.

[0229] The substitution reaction and deprotection in Scheme B2 can be carried out by conventional techniques and methods well known to those skilled in the art.

[0230] The procedure of Scheme B2 can be as follows:

[0231] Step 1: At room temperature, to a 100 mL round-bottom flask were sequentially added compound B-1 (1.0 eq.), compound B-2-1 (1.2 eq.), N,N-diisopropylethylamine (5.0 eq.), and dimethyl sulfoxide. Under a nitrogen atmosphere, the reaction mixture was heated to 130 °C and stirred for 16 hours. After the completion of the reaction was confirmed by TLC, the reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate three times. The organic phases were combined. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford compound B-2-2 (gray solid, yield 62%).

[0232] Step 2: At room temperature, to a solution of compound B-2-2 in dichloromethane in a 100 mL round-bottom flask was added trifluoroacetic acid, and the reaction mixture was stirred for 1 hour. After the completion of the reaction was confirmed by TLC, the reaction mixture was concentrated under reduced pressure, and the resulting residue was lyophilized to afford compound B-2-3.

[0233] Synthesis Scheme C: Scheme C

[0234] In Scheme C, Ra1, Ra2, Ra3, Ra4, Z, (Ra5)m, ring A2, and (Rd4)n4 are as defined in the compounds of Formula (I) of the present disclosure and the respective sub-embodiments thereof.

[0235] Depending upon the target compounds, the above schemes and their reaction substrates, reaction conditions (including reaction dosage, temperature, duration, etc.), work up, etc. can be appropriately modified and adjusted by techniques and methods well known to those skilled in the art to obtain the desired target compounds. The obtained target compounds can be further modified by the substituents and the like to obtain subsequent target compounds through methods well known to those skilled in the art.

[0236] It should be understood that, in each of the above synthetic schemes, when a group contains an active hydrogen or a reactive group that is not intended to participate in the scheme reaction, such active hydrogen or reactive group can be protected by techniques and methods well known to those skilled in the art, for example, using protecting groups. For example, when the reactive group is piperidinyl or piperazinyl, conventional protecting groups such as Boc and the like can be used to protect the hydrogen on the nitrogen. For example, when the reactive group is -CHO, conventional protecting groups can be used to protect the aldehyde group, such as by forming an acetal. The deprotection of the protecting groups can be achieved by techniques and methods well known to those skilled in the art. For example, the removal of the Boc protecting group can be achieved under acidic conditions, such as hydrochloric acid or trifluoroacetic acid. As another example, the removal of the acetal protecting group can be achieved under acidic conditions, such as sulfuric acid, hydrochloric acid, or trifluoroacetic acid. Examples

[0237] Example A-1: Preparation of compound GT-04304

[0238] With reference to the method of Scheme A1, the target compound GT-04304 was obtained (gray solid, 6.5 g, yield 97 %). 1H NMR (400 MHz, MeOD-d4) S 7.57 (d, J = 8.4 Hz, 1H), 7.05 (s, 1H), 6.95 (dd, J = 8.4, 1.8 Hz, 1H), 5.08 (dd, J = 13.3, 5.2 Hz, 1H), 4.44 - 4.31 (m, 2H), 3.38 (t, J = 5.1 Hz, 4H), 3.03 (s, 4H), 2.86 (dd, J = 13.3, 5.3 Hz, 1H), 2.81 - 2.72 (m, 1H), 2.45 (dd, J = 13.1, 4.7 Hz, 1H), 2.17 - 2.09 (m, 1H). LCMS (ESI) calcd. for C17H22N5O3+ [M+H]+: 344.17, found, 344.2.

[0239] Example A-2: Preparation of compound GT-06985

[0240] With reference to the method of Scheme A1, the target compound GT-06985 was obtained (gray solid, 11.7 g, yield 99 %). 1H NMR (400 MHz, MeOD) S 7.49 (d, J = 8.3 Hz, 1H), 7.45 -7.36 (m, 1H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.47 (q, J = 16.7 Hz, 2H), 3.44 - 3.36 (m, 4H), 3.09 (d, J = 4.6 Hz, 4H), 2.95 - 2.85 (m, 1H), 2.81 - 2.75 (m, 1H), 2.48 (qd, J = 13.2, 4.7 Hz, 1H), 2.19 - 2.10 (m, 1H). LCMS (ESI) calcd. for C17H21FN5O3+ [M+H]+: 362.16, found, 362.2.

[0241] Example A-3: Preparation of compound GT-06988

[0242] With reference to the method of Scheme A1, the target compound GT-06988 was obtained (gray solid, 7.9 g, yield 97 %). 1H NMR (400 MHz, DMSO-d6) S 10.96 (s, 1H), 8.74 (s, 2H), 7.73 (s, 1H), 7.36 (d, J = 10.7 Hz, 1H), 7.31 (d, J = 7.2 Hz, 1H), 5.05 (dd, J = 13.3, 5.0 Hz, 1H), 4.32 (d, J = 16.8 Hz, 1H), 4.20 (d, J = 16.9 Hz, 1H), 3.25 (s, 4H), 2.98 (s, 4H), 2.92 - 2.82 (m, 1H), 2.59 (d, J = 17.2 Hz, 1H), 2.36 (dd, J = 13.2, 4.4 Hz, 1H), 2.04 - 1.91 (m, 1H). LCMS (ESI) calcd. for C17H21FN5O3+ [M+H]+: 362.16, found, 362.2.

[0243] Example A-4: Preparation of compound GT-06989

[0244] With reference to the method of Scheme A1, the target compound GT-06989 was obtained (gray solid, 5.4 g, yield 87 %). 1H NMR (400 MHz, MeOD) S 6.77 (s, 1H), 6.65 (d, J = 12.1 Hz, 1H), 5.03 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (q, J = 17.0 Hz, 2H), 3.38 (t, J = 4.8 Hz, 4H), 3.02 (s, 4H), 2.85 (dd, J = 13.3, 5.2 Hz, 1H), 2.79 - 2.69 (m, 1H), 2.42 (dd, J = 13.1, 4.7 Hz, 1H), 2.17 -2.07 (m, 1H). LCMS (ESI) calcd. for C17H21FN5O3+ [M+H]+: 362.16, found, 362.2.

[0245] Example A-5: Preparation of compound GT-07368

[0246] With reference to the method of Scheme A1, the target compound GT-07368 was obtained (gray solid, 5.4 g, yield 98 %). 1H NMR (400 MHz, DMSO-d6) 5 10.98 (s, 1H), 8.78 (s, 2H), 7.30 (t, J = 7.6 Hz, 1H), 7.17 (s, 1H), 7.08 (dd, J = 7.6, 4.4 Hz, 2H), 5.09 (dd, J = 13.2, 5.2 Hz, 1H), 4.36 (d, J = 17.6 Hz, 1H), 4.24 (d, J = 17.6 Hz, 1H), 3.24 (s, 4H), 2.93 (s, 4H), 2.89 (d, J = 5.2 Hz, 1H), 2.62 (d, J = 17.2 Hz, 1H), 2.40 (qd, J = 13.2, 4.4 Hz, 1H), 2.07 - 1.97 (m, 1H). LCMS (ESI) calcd. for C17H22N5O3+ [M+H]+: 344.17, found, 344.1.

[0247] Example A-6: Preparation of compound GT-05579

[0248] With reference to the method of Scheme A1, the target compound GT-05579 was obtained (gray solid, 4.1 g, yield 97 %). 1H NMR (400 MHz, DMSO-d6) 5 11.07 (s, 1H), 8.85 (s, 2H), 8.35 (s, 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.23 (s, 1H), 7.06 (d, J = 7.8 Hz, 1H), 5.05 (dd, J = 12.9, 5.3 Hz, 1H), 3.68 (d, J = 4.3 Hz, 1H), 3.31 (d, J = 18.6 Hz, 4H), 2.88 (td, J = 14.6, 5.2 Hz, 4H), 2.56 (dd, J = 20.1, 10.7 Hz, 2H), 2.01 (dd, J = 9.9, 4.8 Hz, 1H). LCMS (ESI) calcd. for C17H20N5O4+ [M+H]+: 358.15, found, 358.1.

[0249] Example A-7: Preparation of compound GT-04310

[0250] With reference to the method of Scheme B1, the target compound GT-04310 was obtained (pale yellow solid, 1.5 g, yield 96 %). 1H NMR (400 MHz, DMSO-d6) 5 11.09 (s, 1H), 8.84 (s, 1H), 8.42 (s, 1H), 7.65 (d, J = 10.3 Hz, 1H), 7.57 (d, J = 7.0 Hz, 1H), 5.08 (dd, J = 12.8, 5.4 Hz, 1H), 3.30 (s, 4H), 2.97 (d, J = 33.3 Hz, 4H), 2.93 - 2.83 (m, 1H), 2.56 (dd, J = 22.6, 11.2 Hz, 2H), 2.05 - 1.97 (m, 1H). LCMS (ESI) calcd. for C17H19FN5O4+ [M+H]+: 376.14, found, 376.2.

[0251] Example A-8: Preparation of compound GT-07007

[0252] With reference to the method of Scheme B2, the target compound GT-07007 was obtained (gray solid, 3.6 g, yield 92 %). 1H NMR (400 MHz, DMSO-d6) 5 11.09 (s, 1H), 9.48 (s, 2H), 7.74 (d, J = 8.5 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.30 (dd, J = 8.5, 2.0 Hz, 1H), 5.09 (dd, J = 12.9, 5.4 Hz, 1H), 3.58 (s, 4H), 3.02 (s, 4H), 2.92 - 2.83 (m, 1H), 2.57 (dd, J = 19.3, 10.3 Hz, 2H), 2.08 -1.99 (m, 1H). LCMS (ESI) calcd. for C17H20N5O4+ [M+H]+: 358.15, found, 358.2.

[0253] Example A-9: Preparation of compound GT-07051

[0254] With reference to the method of Scheme B2, the target compound GT-07051 was obtained (gray solid, 1.6 g, yield 97 %). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 9.65 (s, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.13 - 7.06 (m, 2H), 5.05 (dd, J = 13.3, 5.1 Hz, 1H), 4.34 (d, J = 17.0 Hz, 1H), 4.23 (t, J = 17.0 Hz, 1H), 3.46 - 3.30 (m, 4H), 3.11 (brs, 4H), 2.94 - 2.84 (m, 1H), 2.58 (d, J = 17.2 Hz, 1H), 2.43 - 2.31 (m, 1H), 1.98 - 1.90 (m, 1H). LCMS (ESI) calcd. for C17H22N5O3+ [M+H]+: 344.17, found, 344.2.

[0255] Example A-10: Preparation of compound GT-07008

[0256] The target compound GT-07008 was prepared according to the method of Scheme C.

[0257] Step 1: to a solution of (1-aminopiperidin-4-yl)methanol (1.0 eq.) in 1,4-dioxane in a 100 mL single-neck flask were added sequentially (Boc)2O (1.2 eq.) and triethylamine (3.0 eq.). The reaction mixture was stirred at room temperature for 16 hours. After the completion of the reaction was confirmed by TLC, the reaction mixture was concentrated under reduced pressure. The resulting residue was washed with water and extracted with ethyl acetate three times. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate = 0-50%) to give tert-butyl (4-(hydroxymethyl)piperidin-1-yl)carbamate as a white solid (yield: 80%).

[0258] Step 2: To a solution of tert-butyl (4-(hydroxymethyl)piperidin-1-yl)carbamate (1.0 eq.) in dichloromethane in a 100 mL single-neck flask were added sequentially MsCl (1.2 eq.) and triethylamine (3.0 eq.). The reaction mixture was stirred at room temperature for 1 hour. After the completion of the reaction was confirmed by TLC, the reaction mixture was washed with water and extracted with dichloromethane three times. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate = 0-40%) to give (1-((tert-butoxycarbonyl)amino)piperidin-4-yl)methyl methanesulfonate as a white solid (yield: 85%).

[0259] Step 3: To a solution of (1-((tert-butoxycarbonyl)amino)piperidin-4-yl)methyl methanesulfonate (1.3 eq.) and 3-(5-mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione (1.0 eq.) in dimethyl sulfoxide in a 100 mL single-neck flask was added triethylamine (3.0 eq.). The reaction mixture was stirred at room temperature for 16 hours. After the completion of the reaction was confirmed by TLC, the reaction mixture was washed with water and extracted with ethyl acetate three times. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate = 0-50%) to give tert-butyl (4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)methyl)piperidin-1-yl)carbamate as a white solid (yield: 50%).

[0260] Step 4: At room temperature, to a solution of tert-butyl (4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)methyl)piperidin-1-yl)carbamate in dichloromethane in a 100 mL single-neck flask was added trifluoroacetic acid. The reaction mixture was stirred for 1 hour. After the completion of the reaction was confirmed by TLC, the reaction mixture was concentrated under reduced pressure and lyophilized to afford compound GT-07008 (gray solid, 0.6 g, yield 93 %). 1H NMR (400 MHz, MeOD-d4) 5 11.80 (s, 1H), 10.03 (s, 1H), 8.48 - 8.43 (m, 1H), 8.38 (s, 1H), 8.25 (d, J = 7.1 Hz, 1H), 5.91 (dd, J = 13.3, 5.1 Hz, 1H), 5.17 (dd, J = 50.0, 17.4 Hz, 2H), 4.26 (s, 4H), 3.86 (d, J = 6.1 Hz, 2H), 3.77 - 3.68 (m, 1H), 3.42 (d, J = 17.0 Hz, 1H), 3.30 - 3.12 (m, 2H), 2.89 - 2.68 (m, 3H), 2.27 - 2.16 (m, 2H). LCMS (ESI) calcd. for C19H25N4O3S+ [M+H]+: 389.16, found, 389.2.

[0261] Example A-11: Preparation of compound GT-07966

[0262] With reference to the method of Scheme A1, the target compound GT-07966 was obtained (yellow solid, 1.56 g, yield 94 %). 1H NMR(400 MHz, DMSO-d6) 5 10.93 (s, 1H), 8.99 (s, 2H), 7.56 (s, 1H), 7.46 (d, J = 8.4 Hz, 1H), 6.94(s, 1H), 6.87 (d, J = 8.4 Hz, 1H), 5.03 (dd, J = 13.2, 5.2 Hz, 1H), 4.31 (d, J = 16.8 Hz, 1H), 4.18 (d, J =16.8 Hz, 1H), 4.08 - 4.01 (m, 2H), 2.99 - 2.82 (m, 5H), 2.58 (d,J = 16.8 Hz, 1H), 2.33 (dd, J = 13.2, 4.4 Hz, 1H), 2.15 (d, J = 8.8 Hz, 2H), 1.98 - 1.89 (m, 3H). LCMS (ESI) calcd. for C 19H24N5O3+: 370.19, found, 370.1.

[0263] Example A-12: Preparation of compound GT-08008

[0264] With reference to the method of Scheme A1, the target compound GT-08008 was obtained (yellow solid, 1.7 g, yield 83 %). 1H NMR(400 MHz, DMSO-d6) 8 10.93 (s, 1H), 9.49 (s, 1H), 7.98 (s, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.03(s, 1H), 6.96 (d, J = 8.4 Hz, 1H), 5.03 (dd, J = 13.2, 5.2 Hz, 1H), 4.30 (dd, J = 11.2, 5.6 Hz, 3H), 4.18 (d, J = 16.8 Hz, 1H), 3.46 (d, J = 10.4 Hz, 2H), 3.34 (d, J = 11.2 Hz, 2H), 2.96 - 2.85 (m, 1H), 2.75 - 2.64 (m,1H), 2.58 (d, J = 16.8 Hz, 1H), 2.35 (ddd, J = 26.0, 13.2, 4.4 Hz, 2H), 1.98 - 1.91 (m, 1H). LCMS (ESI) calcd. for C 18H22N5O3+: 356.16, found, 356.1.

[0265] Example A-13: Preparation of compound GT-08009

[0266] With reference to the method of Scheme A1, the target compound GT-08009 was obtained (yellow solid, 1.2 g, yield 75 %). 1H NMR(400 MHz, DMSO-d6) 8 10.93 (s, 1H), 9.03 (s, 1H), 8.77 (s, 1H), 7.72 (s, 1H), 7.45 (d, J = 8.4Hz, 1H), 6.96 (s, 1H), 6.86 (d, J = 8.4 Hz, 1H), 5.03 (dd, J = 13.2, 5.2 Hz, 1H), 4.30 (d, J = 16.4 Hz, 2H),4.17 (d, J = 16.8 Hz, 1H), 3.63 (s, 1H), 3.15 (s, 2H), 3.07 - 2.77 (m, 2H), 2.58 (d, J = 16.8 Hz, 1H), 2.39 -2.14 (m, 2H), 1.95 (dd, J = 9.2, 3.6 Hz, 1H), 1.75 (d, J = 10.8 Hz, 1H), 0.83 (dd, J = 9.6, 6.8 Hz, 1H). LCMS (ESI) calcd. for C 18H22N5O3+: 356.17, found, 356.1.

[0267] Example A-14: Preparation of compound GT-08007

[0268] With reference to the method of Scheme A1, the target compound GT-08007 was obtained (brown solid, 1.1 g, yield 99 %). 1H NMR (400 MHz, DMSO-d6) 8 10.94 (s, 1H), 8.91 (s, 2H), 7.73 (s, 1H), 7.45 (d, J = 8.4 Hz, 1H), 6.96 (s, 1H), 6.87 (d, J = 8.4 Hz, 1H), 5.03 (dd, J = 13.2, 5.2 Hz, 1H), 4.31 (d, J = 16.8 Hz, 1H), 4.18 (d, J = 16.8 Hz, 1H), 3.26 (d, J = 4.8 Hz, 4H), 3.12 (s, 2H), 2.91 (ddd, J = 18.4, 13.6, 6.4 Hz, 3H), 2.59 (d, J = 16.8 Hz, 1H), 2.35 (qd, J = 13.2, 4.4 Hz, 1H), 2.04 - 1.82 (m, 3H). LCMS (ESI) calcd. for C 18H24N5O3+ [M+H]+: 358.18, found, 358.2.

[0269] Example A-15: Preparation of compound GT-08006

[0270] With reference to the method of Scheme A1, the target compound GT-08006 was obtained (brown solid, 980 mg, yield 95%). 1H NMR (400 MHz, DMSO-d6) 8 10.99 (s, 1H), 9.02 (s, 2H), 7.49 (d, J = 8.4 Hz, 1H), 7.28 (d, J = 16.8 Hz, 1H), 6.94 (s, 1H), 6.88 (d, J = 8.4 Hz, 1H), 5.08 (dd, J = 13.2, 5.2 Hz, 1H), 4.35 (d, J = 16.8 Hz, 1H), 4.21 (d, J = 16.8 Hz, 1H), 3.80 (t, J = 6.0 Hz, 4H), 3.01 - 2.90 (m, 1H), 2.64 (d, J = 16.8 Hz, 5H), 2.39 (ddd, J = 26.0, 13.2, 4.4 Hz, 1H), 1.99 (dd, J = 17.6, 10.4 Hz, 5H). LCMS (ESI) calcd. for C20H26N5O3+ [M+H]+: 384.20, found, 384.3.

[0271] Example A-16: Preparation of compound GT-07965

[0272] With reference to the method of Scheme A1, the target compound GT-07965 was obtained (off-white solid, 1.1 g, yield 99 %). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 8.93 (s, 1H), 8.76 (s, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.24 (s, 1H), 6.95 (s, 1H), 6.89 (d, J = 8.0 Hz, 1H), 5.03 (dd, J = 13.2, 4.8 Hz, 1H), 4.29 (d, J = 16.8 Hz, 1H), 4.19 (s, 1H), 3.47 (s, 2H), 3.10 - 2.82 (m, 7H), 2.68 (s, 2H), 2.59 (d, J = 17.6 Hz, 1H), 2.34 (dt, J = 22.4, 11.2 Hz, 1H), 2.02 - 1.90 (m, 1H). LCMS (ESI) calcd. for C19H24N5O3+ [M+H]+: 370.18, found, 370.1.

[0273] Example 1: Preparation of compound GT-06422

[0274] With reference to the method of Scheme 2, the target compound GT-06422 was obtained (white solid, 15 mg, yield 25 %). 1H NMR (400 MHz, DMSO-d6) 5 11.66 (s, 1H), 11.07 (s, 1H), 7.95 - 7.79 (m, 3H), 7.63 (d, J = 8.2 Hz, 1H), 7.54 - 7.30 (m, 7H), 7.23 - 7.19 (m, 1H), 7.08 -6.96 (m, 1H), 5.05 (dd, J = 12.6, 5.3 Hz, 1H), 3.30 - 3.15 (m, 6H), 3.15 - 3.01 (m, 2H), 2.96 -2.78 (m, 2H), 2.58 (d, J = 17.6 Hz, 1H), 2.45 - 2.33 (m, 1H), 2.05 - 1.95 (m, 1H). LCMS (ESI) calcd. for C30H30N5O4+ [M+H]+: 524.23, found, 524.3.

[0275] Example 2: Preparation of compound GT-06401

[0276] With reference to the method of Scheme 2, the target compound GT-06401 was obtained (white solid, 10 mg, yield 16 %). 1H NMR (400 MHz, DMSO-d6) 5 10.99 (s, 1H), 7.87 - 7.73 (m, 1H), 7.68 - 7.53 (m, 2H), 7.48 - 7.39 (m, 2H), 7.36 - 7.23 (m, 2H), 7.22 - 7.05 (m, 3H), 6.97 -6.93 (m, 1H), 4.97 (dd, J = 12.7, 5.5 Hz, 1H), 3.21 - 3.11 (m, 4H), 3.11 - 2.91 (m, 4H), 2.80 -2.76 (m, 2H), 2.53 - 2.48 (m, 1H), 2.41 - 2.33 (m, 1H), 1.99 - 1.87 (m, 1H). LCMS (ESI) calcd. for C30H28F2N5O4+ [M+H]+: 560.21, found, 560.2.

[0277] Example 3: Preparation of compound GT-06509

[0278] With reference to the method of Scheme 2, the target compound GT-06509 was obtained (white solid, 41 mg, yield 66 %). 1H NMR (400 MHz, DMSO-d6) 5 11.00 (s, 1H), 9.69 (s, 1H), 8.30 (s, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.19 - 7.12 (m, 4H), 6.95 (d, J = 7.6 Hz, 1H), 4.97 (dd, J = 12.7, 5.3 Hz, 1H), 3.61 - 3.48 (m, 2H), 3.05 - 2.73 (m, 8H), 2.51 (d, J = 18.1 Hz, 1H), 2.48 - 2.46 (m, 1H), 2.20 (brs, 5H), 1.99 - 1.86 (m, 1H), 1.64 (brs, 4H). LCMS (ESI) calcd. for C30H33FN5O4+ [M+H]+: 546.25, found, 546.3.

[0279] Example 4: Preparation of compound GT-07045

[0280] With reference to the method of Scheme 1, the target compound GT-07045 was obtained (white solid, 34 mg, yield 53 %). 1H NMR (400 MHz, DMSO-d6) 8 10.99 (s, 1H), 10.17 (s, 1H), 8.32 (s, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.43 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.3 Hz, 2H), 7.12 (s, 1H), 6.95 (s, 1H), 4.97 (dd, J = 12.8, 5.4 Hz, 1H), 4.30 (s, 2H), 3.76 (t, J = 5.3 Hz, 2H), 3.61 (s, 2H), 3.39 - 3.31 (m, 2H), 3.07 - 3.01 (m, 2H), 2.98 - 2.85 (m, 4H), 2.81 - 2.76 (m, 1H), 2.49 -2.43 (m, 2H), 2.30 (s, 2H), 1.96 - 1.89 (m, 1H). LCMS (ESI) calcd. for C29H31ClNsO5+ [M+H]+: 564.20, found, 564.2.

[0281] Example 5: Preparation of compound GT-06423

[0282] With reference to the method of Scheme 2, the target compound GT-06423 was obtained (white solid, 14 mg, yield 24 %). 1H NMR (400 MHz, DMSO-d6) 8 11.37 (s, 1H), 11.09 (s, 1H), 7.94 - 7.74 (m, 3H), 7.64 (d, J = 10.2 Hz, 1H), 7.60 - 7.26 (m, 8H), 5.07 (dd, J = 12.9, 5.3 Hz, 1H), 3.31 - 3.17 (m, 6H), 3.13 - 3.06 (m, 2H), 2.94 - 2.83 (m, 2H), 2.59 (d, J = 19.6 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.07 - 1.96 (m, 1H). LCMS (ESI) calcd. for C30H29FN5O4+ [M+H]+: 542.22, found, 542.3.

[0283] Example 6: Preparation of compound GT-06402

[0284] With reference to the method of Scheme 2, the target compound GT-06402 was obtained (white solid, 14 mg, yield 22 %). 1H NMR (400 MHz, DMSO-d6) 8 11.09 (s, 1H), 7.96 - 7.78 (m, 1H), 7.64 (d, J = 10.3 Hz, 2H), 7.59 - 7.41 (m, 4H), 7.34 - 7.01 (m, 3H), 5.07 (dd, J = 12.6, 5.4 Hz, 1H), 3.29 - 3.17 (m, 4H), 3.17 - 2.95 (m, 4H), 2.95 - 2.81 (m, 2H), 2.61 - 2.56 (m, 2H), 2.49 - 2.38 (m, 1H), 2.06 - 1.94 (m, 1H). LCMS (ESI) calcd. for C30H27F3N5O4+ [M+H]+: 578.20, found, 578.2.

[0285] Example 7: Preparation of compound GT-06510

[0286] With reference to the method of Scheme 2, the target compound GT-06510 was obtained (white solid, 41 mg, yield 67 %). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 9.68 (s, 1H), 8.41 (s, 1H), 7.64 (d, J = 10.3 Hz, 1H), 7.52 (d, J = 6.9 Hz, 1H), 7.27 - 7.20 (m, 3H), 5.06 (dd, J = 12.8, 5.4 Hz, 1H), 3.65 - 3.58 (m, 2H), 3.21 - 3.13 (m, 2H), 3.10 - 3.05 (m, 1H), 3.04 - 2.78 (m, 6H), 2.58 (d, J = 19.8 Hz, 1H), 2.39 - 2.20 (m, 5H), 2.06 - 1.96 (m, 1H), 1.71 (brs, 4H). LCMS (ESI) calcd. for C30H32F2N5O4+ [M+H]+: 564.24, found, 564.3.

[0287] Example 8: Preparation of compound GT-06961

[0288] With reference to the method of Scheme 1, the target compound GT-06961 was obtained (white solid, 15 mg, yield 24 %). 1H NMR (400 MHz, DMSO-d6) 8 11.01 (s, 1H), 9.89 (s, 1H), 8.34 (s, 1H), 7.56 (d, J = 10.3 Hz, 1H), 7.43 (d, J = 7.7 Hz, 3H), 7.19 (d, J = 8.2 Hz, 2H), 4.99 (dd, J = 12.8, 5.4 Hz, 1H), 4.27 (s, 2H), 3.77 (t, J = 5.1 Hz, 2H), 3.62 (s, 2H), 3.44 - 3.38 (m, 2H), 3.16 - 3.03 (m, 2H), 3.03 - 2.84 (m, 4H), 2.83 - 2.77 (m, 1H), 2.53 - 2.46 (m, 2H), 2.30 (s, 2H), 2.00 - 1.86 (m, 1H). LCMS (ESI) calcd. for C29H30ClFN5O5+ [M+H]+: 582.19, found, 582.2.

[0289] Example 9: Preparation of compound GT-06398

[0290] With reference to the method of Scheme 2, the target compound GT-06398 was obtained (white solid, 14 mg, yield 22 %). 1H NMR (400 MHz, DMSO-d6) 8 10.86 (s, 1H), 7.88 - 7.78 (m, 1H), 7.70 - 7.59 (m, 2H), 7.53 - 7.41 (m, 2H), 7.38 (d, J = 8.4 Hz, 1H), 7.35 - 7.26 (m, 1H), 7.24 - 7.10 (m, 2H), 6.85 (s, 1H), 6.79 (d, J = 8.6 Hz, 1H), 4.95 (dd, J = 13.2, 5.2 Hz, 1H), 4.22 (d, J = 16.9 Hz, 1H), 4.09 (d, J = 16.9 Hz, 1H), 3.24 - 3.09 (m, 4H), 3.06 - 2.93 (m, 2H), 2.87 - 2.85 (m, 3H), 2.66 (s, 1H), 2.51 (d, J = 17.8 Hz, 1H), 2.32 - 2.22 (m, 1H), 1.95 - 1.81 (m, 1H). LCMS (ESI) calcd. for C30H30F2N5O3+ [M+H]+: 546.23, found, 546.2.

[0291] Example 10: Preparation of compound GT-06426

[0292] With reference to the method of Scheme 2, the target compound GT-06426 was obtained (white solid, 18 mg, yield 28 %). 1H NMR (400 MHz, DMSO-d6) 8 10.86 (s, 1H), 7.96 - 7.75 (m, 3H), 7.66 - 7.58 (m, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.33 - 7.14 (m, 4H), 6.85 (s, 1H), 6.82 - 6.72 (m, 1H), 4.95 (dd, J = 13.3, 5.1 Hz, 1H), 4.22 (d, J = 17.0 Hz, 1H), 4.09 (d, J = 16.9 Hz, 1H), 3.19 - 3.08 (m, 4H), 3.07 - 2.95 (m, 4H), 2.87 - 2.77 (m, 2H), 2.51 (d, J = 17.2 Hz, 1H), 2.32 - 2.22 (m, 1H), 1.96 - 1.80 (m, 1H). LCMS (ESI) calcd. for C30H30F2N5O3+ [M+H]+: 546.23, found, 546.2.

[0293] Example 11: Preparation of compound GT-06427

[0294] With reference to the method of Scheme 2, the target compound GT-06427 was obtained (white solid, 23 mg, yield 34 %). 1H NMR (400 MHz, DMSO-d6) 8 10.86 (s, 1H), 7.91 - 7.74 (m, 2H), 7.58 - 7.27 (m, 7H), 6.84 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 4.95 (dd, J = 13.4, 5.0 Hz, 1H), 4.22 (d, J = 16.7 Hz, 1H), 4.09 (d, J = 17.0 Hz, 1H), 3.20 - 3.12 (m, 4H), 3.04 - 2.92 (m, 4H), 2.89 - 2.77 (m, 2H), 2.51 (d, J = 17.6 Hz, 1H), 2.31 - 2.22 (m, 1H), 1.91 - 1.84 (m, 1H). LCMS (ESI) calcd. for C30H30Cl2N5O3+ [M+H]+: 578.17, found, 578.2.

[0295] Example 12: Preparation of compound GT-06428

[0296] With reference to the method of Scheme 2, the target compound GT-06428 was obtained (white solid, 23 mg, yield 35%). 1H NMR (400 MHz, DMSO-d6) 5 11.12 (s, 1H), 10.86 (s, 1H), 7.66 (d, J = 8.4 Hz, 4H), 7.39 (d, J = 8.2 Hz, 1H), 6.94 (d, J = 8.4 Hz, 4H), 6.86 (s, 1H), 6.79 (d, J = 8.6 Hz, 1H), 5.40 (d, J = 9.4 Hz, 1H), 4.96 (dd, J = 13.2, 5.2 Hz, 1H), 4.22 (d, J = 16.9 Hz, 1H), 4.09 (d, J = 17.0 Hz, 1H), 3.68 (s, 6H), 3.19 - 3.09 (m, 4H), 3.01 (s, 4H), 2.87 - 2.80 (m, 1H), 2.51 (d, J = 17.4 Hz, 1H), 2.31 - 2.25 (m, 1H), 1.95 - 1.79 (m, 1H). LCMS (ESI) calcd. for C32H35N5NaO5+ [M+Na]+: 592.25, found, 592.3.

[0297] Example 13: Preparation of compound GT-06499

[0298] With reference to the method of Scheme 1, the target compound GT-06499 was obtained (white solid, 29 mg, yield 46%). 1H NMR (400 MHz, DMSO-d6) 5 10.87 (s, 1H), 10.62 (s, 1H), 7.91 (s, 1H), 7.74 - 7.70 (m, 2H), 7.60 (s, 1H), 7.50 (d, J = 8.6 Hz, 4H), 7.40 (d, J = 8.3 Hz, 1H), 6.86 (s, 1H), 6.79 (d, J = 8.3 Hz, 1H), 4.96 (dd, J = 13.2, 5.1 Hz, 1H), 4.35 (d, J = 3.8 Hz, 2H), 4.23 (d, J = 16.9 Hz, 1H), 4.10 (d, J = 17.0 Hz, 1H), 3.26 - 3.22 (m, 4H), 3.10 - 3.03 (m, 2H), 2.95 - 2.78 (m, 3H), 2.52 (d, J = 16.4 Hz, 1H), 2.32 - 3.23 (m, 1H), 1.92 - 1.87 (m, 1H). LCMS (ESI) calcd. for C30H31ClN5O3+ [M+H]+: 544.21, found, 544.2.

[0299] Example 14: Preparation of compound GT-06500

[0300] With reference to the method of Scheme 1, the target compound GT-06500 was obtained (white solid, 32 mg, yield 51%). 1H NMR (400 MHz, DMSO-d6) 5 10.87 (s, 1H), 10.57 (s, 1H), 7.74 - 7.67 (m, 4H), 7.63 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.40 (d, J = 8.4 Hz, 1H), 6.86 (s, 1H), 6.80 (d, J = 8.3 Hz, 1H), 4.96 (dd, J = 13.3, 5.0 Hz, 1H), 4.32 (brs, 2H), 4.23 (d, J = 17.0 Hz, 1H), 4.10 (d, J = 17.0 Hz, 1H), 3.27 - 3.16 (m, 4H), 3.10 - 3.00 (m, 2H), 2.94 - 2.77 (m, 3H), 2.52 (d, J = 17.3 Hz, 1H), 2.34 - 2.21 (m, 1H), 1.94 - 1.83 (m, 1H). LCMS (ESI) calcd. for C30H31ClN5O3+ [M+H]+: 544.21, found, 544.2.

[0301] Example 15: Preparation of compound GT-06505

[0302] With reference to the method of Scheme 2, the target compound GT-06505 was obtained (white solid, 20 mg, yield 32%). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.24 - 7.16 (m, 4H), 6.90 (s, 1H), 6.84 (d, J = 8.2 Hz, 1H), 5.02 (dd, J = 13.3, 5.2 Hz, 1H), 4.28 (d, J = 16.9 Hz, 1H), 4.15 (d, J = 16.9 Hz, 1H), 2.94 - 2.82 (m, 5H), 2.59 (d, J = 17.4 Hz, 1H), 2.32 - 2.25 (m, 7H), 1.98 - 1.93 (m, 1H), 1.71 - 1.64 (m, 8H). LCMS (ESI) calcd. for C30H35FN5O3+ [M+H]+: 532.27, found, 532.3.

[0303] Example 16: Preparation of compound GT-06501

[0304] With reference to the method of Scheme 1, the target compound GT-06501 was obtained (white solid, 12 mg, yield 19%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 10.26 (s, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.35 - 7.21 (m, 4H), 6.89 (s, 1H), 6.83 (d, J = 8.9 Hz, 1H), 5.02 (dd, J = 13.2, 4.7 Hz, 1H), 4.37 (s, 2H), 4.28 (d, J = 16.8 Hz, 1H), 4.14 (d, J = 16.8 Hz, 1H), 3.84 (t, J = 5.1 Hz, 2H), 3.65 (s, 2H), 3.05 - 2.83 (m, 7H), 2.61 - 2.54 (m, 2H), 2.44 - 2.29 (m, 4H), 2.01 -1.88 (m, 1H). LCMS (ESI) calcd. for C29H33FN5O4+ [M+H]+: 534.25, found, 534.3.

[0305] Example 17: Preparation of compound GT-06511

[0306] With reference to the method of Scheme 1, the target compound GT-06511 was obtained (white solid, 22 mg, yield 34%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 10.18 (s, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 6.90 (s, 1H), 6.84 (d, J = 8.0 Hz, 1H), 5.02 (dd, J = 13.2, 5.0 Hz, 1H), 4.36 (s, 2H), 4.28 (d, J = 16.8 Hz, 1H), 4.14 (d, J = 16.9 Hz, 1H), 3.84 (t, J = 5.4 Hz, 2H), 3.72 - 3.62 (m, 2H), 3.17 - 2.76 (m, 8H), 2.58 (d, J = 18.9 Hz, 1H), 2.56 - 2.53 (m, 1H), 2.41 - 2.33 (m, 3H), 1.99 - 1.93 (m, 1H). LCMS (ESI) calcd. for C29H33ClN5O4+ [M+H]+: 550.22, found, 550.3.

[0307] Example 18: Preparation of compound GT-06502

[0308] With reference to the method of Scheme 1, the target compound GT-06502 was obtained (white solid, 19 mg, yield 28%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 10.20 (s, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 6.90 (s, 1H), 6.84 (d, J = 8.4 Hz, 1H), 5.02 (dd, J = 13.3, 5.0 Hz, 1H), 4.37 (s, 2H), 4.28 (d, J = 17.0 Hz, 1H), 4.14 (d, J = 16.9 Hz, 1H), 3.67 (brs, 2H), 3.06 - 2.83 (m, 7H), 2.64 - 2.52 (m, 3H), 2.35 - 2.32 (m, 1H), 2.24 (s, 2H), 2.00 - 1.88 (m, 1H), 1.23 (s, 6H). LCMS (ESI) calcd. for C31H37ClN5O4+ [M+H]+: 578.25, found, 578.3.

[0309] Example 19: Preparation of compound GT-06420 (white solid, 18 mg, yield 30%). 1H NMR (400 MHz, DMSO-d6) 5 11.29 (s, 1H), 10.89 (s, 1H), 7.80 - 7.73 (m, 2H), 7.48 - 7.38 (m, 4H), 7.37 - 7.29 (m, 4H), 7.27 - 7.13 (m, 2H), 5.55 (s, 1H), 4.97 (dd, J = 13.3, 4.9 Hz, 1H), 4.38 (d, J = 16.9 Hz, 1H), 4.20 (d, J = 16.7 Hz, 1H), 3.53 - 3.44 (m, 1H), 3.18 - 3.07 (m, 4H), 3.04 - 2.98 (m, 2H), 2.87 - 2.78 (m, 2H), 2.52 (d, J = 18.1 Hz, 1H), 2.34 - 2.26 (m, 1H), 1.93 - 1.85 (m, 1H). LCMS (ESI) calcd. for C30H31FN5O3+ [M+H]+: 528.24, found, 528.3.

[0311] Example 20: Preparation of compound GT-06399

[0312] With reference to the method of Scheme 1, the target compound GT-06399 was obtained (white solid, 11 mg, yield 17%). 1H NMR (400 MHz, DMSO-d6) 5 10.89 (s, 1H), 7.83 - 7.72 (m, 1H), 7.70 - 7.51 (m, 2H), 7.51 - 7.38 (m, 2H), 7.36 - 7.28 (m, 2H), 7.26 - 7.05 (m, 3H), 4.97 (dd, J = 13.2, 4.9 Hz, 1H), 4.38 (d, J = 16.8 Hz, 1H), 4.20 (d, J = 16.7 Hz, 1H), 3.22 - 3.10 (m, 4H), 3.07 - 2.98 (m, 2H), 2.88 - 2.75 (m, 3H), 2.66 (s, 1H), 2.51 (d, J = 17.5 Hz, 1H), 2.36 - 2.24 (m, 1H), 1.94 - 1.83 (m, 1H). LCMS (ESI) calcd. for C30H29F3N5O3+ [M+H]+: 564.22, found, 564.2.

[0313] Example 21: Preparation of compound GT-06506

[0314] With reference to the method of Scheme 2, the target compound GT-06506 was obtained (white solid, 13 mg, yield 22%). 1H NMR (400 MHz, DMSO-d6) 5 10.89 (s, 1H), 9.50 (s, 1H), 7.64 (s, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.19 - 7.13 (m, 4H), 4.97 (dd, J = 13.2, 5.1 Hz, 1H), 4.38 (d, J = 16.7 Hz, 1H), 4.20 (d, J = 16.8 Hz, 1H), 3.56 - 3.48 (m, 2H), 3.07 - 2.95 (m, 4H), 2.92 -2.82 (m, 4H), 2.52 (d, J = 17.4 Hz, 1H), 2.38 - 2.24 (m, 2H), 2.19 (brs, 4H), 1.92 - 1.83 (m, 1H), 1.64 (brs, 4H). LCMS (ESI) calcd. for C30H34F2N5O3+ [M+H]+: 550.26, found, 550.3.

[0315] Example 22: Preparation of compound GT-06507

[0316] With reference to the method of Scheme 2, the target compound GT-06507 was obtained (white solid, 33 mg, yield 54%). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 9.90 (s, 1H), 7.72 (s, 1H), 7.34 (d, J = 10.7 Hz, 1H), 7.24 (d, J = 8.5 Hz, 4H), 5.03 (dd, J = 13.2, 5.1 Hz, 1H), 4.29 (d, J = 16.9 Hz, 1H), 4.16 (d, J = 16.9 Hz, 1H), 3.63 - 3.58 (m, 2H), 3.15 - 2.95 m, 3H), 2.94 - 2.86 (m, 5H), 2.59 (d, J = 16.8 Hz, 1H), 2.35 - 2.21 (m, 6H), 1.97 - 1.93(m, 1H), 1.71 (brs, 4H). LCMS (ESI) calcd. for C30H34F2N5O3+ [M+H]+: 550.26, found, 550.3.

[0317] Example 23: Preparation of compound GT-06421 (white solid, 12 mg, yield 20%). 1H NMR (400 MHz, DMSO-d6) 5 11.61 (s, 1H), 10.95 (s, 1H), 8.13 - 7.98 (m, 1H), 7.97 - 7.81 (m, 3H), 7.51 - 7.38 (m, 6H), 6.74 - 6.65 (m, 1H), 6.62 - 6.58 (m, 1H), 4.98 (dd, J = 13.3, 5.1 Hz, 1H), 4.31 (d, J = 17.3 Hz, 1H), 4.17 (d, J = 16.9 Hz, 1H), 3.60 - 3.52 (m, 1H), 3.26 - 3.14 (m, 4H), 3.11 - 3.05 (m, 3H), 2.97 - 2.80 (m, 2H), 2.58 (d, J = 17.7 Hz, 1H), 2.34 - 2.29 (m, 1H), 2.00 - 1.89 (m, 1H). LCMS (ESI) calcd. for C30H31FN5O3+ [M+H]+: 528.24, found, 528.2.

[0319] Example 24: Preparation of compound GT-06400

[0320] With reference to the method of Scheme 2, the target compound GT-06400 was obtained (white solid, 24 mg, yield 38%). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 8.17 - 8.13 (m, 1H), 7.94 - 7.79 (m, 1H), 7.77 - 7.62 (m, 1H), 7.59 - 7.35 (m, 4H), 7.31 - 7.12 (m, 2H), 6.68 (s, 1H), 6.65 - 6.50 (m, 1H), 4.98 (dd, J = 13.2, 5.0 Hz, 1H), 4.31 (d, J = 17.2 Hz, 1H), 4.17 (d, J = 16.9 Hz, 1H), 3.28 - 3.17 (m, 4H), 3.13 - 3.04 (m, 2H), 2.94 - 2.84 (m, 3H), 2.74 (s, 1H), 2.58 (d, J = 16.3 Hz, 1H), 2.36 - 2.25 (m, 1H), 2.01 - 1.88 (m, 1H). LCMS (ESI) calcd. for C30H29F3N5O3+ [M+H]+: 564.22, found, 564.3.

[0321] Example 25: Preparation of compound GT-06508

[0322] With reference to the method of Scheme 2, the target compound GT-06508 was obtained (white solid, 38 mg, yield 62%). 1H NMR (400 MHz, DMSO-d6) 5 10.87 (s, 1H), 10.19 (s, 1H), 7.97 (s, 1H), 7.16 (dd, J = 13.1, 4.4 Hz, 3H), 6.59 (s, 1H), 6.52 (d, J = 12.1 Hz, 1H), 4.91 (dd, J = 13.3, 5.1 Hz, 1H), 4.22 (d, J = 17.3 Hz, 1H), 4.08 (d, J = 17.3 Hz, 1H), 3.54 - 3.45 (m, 2H), 3.13 - 2.95 (m, 3H), 2.91 - 2.73 (m, 5H), 2.56 - 2.46 (m, 1H), 2.36 - 2.12 (m, 6H), 1.96 - 1.82 (m, 1H), 1.63 (s, 4H). LCMS (ESI) calcd. for C30H34F2N5O3+ [M+H]+: 550.26, found, 550.3.

[0323] Example 26: Preparation of compound GT-06863

[0324] With reference to the method of Scheme 4, the target compound GT-06863 was obtained (white solid, 25 mg, yield 36%). 1H NMR (400 MHz, DMSO-d6) 5 10.86 (s, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 4.4 Hz, 2H), 7.14 - 7.05 (m, 1H), 6.87 (s, 1H), 6.79 (d, J = 8.1 Hz, 1H), 4.96 (dd, J = 13.2, 5.0 Hz, 1H), 4.24 (d, J = 16.9 Hz, 1H), 4.10 (d, J = 16.9 Hz, 1H), 3.34 - 3.14 (m, 9H), 2.98 - 2.87 (m, 4H), 2.88 - 2.77 (m, 1H), 2.70 - 2.61 (m, 3H), 2.52 (d, J = 16.8 Hz, 1H), 2.34 - 2.21 (m, 1H), 1.92 - 1.87 (m, 1H). LCMS (ESI) calcd. for C28H32Cl2N7O4+ [M+H]+: 600.19, found, 600.2.

[0325] Example 27: Preparation of compound GT-06864

[0326] With reference to the method of Scheme 4, the target compound GT-06864 was obtained (white solid, 26 mg, yield 41%). 1H NMR (400 MHz, DMSO-d6) 5 10.87 (s, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.29 (s, 2H), 7.14 (t, J = 8.7 Hz, 2H), 6.91 (s, 1H), 6.83 (d, J = 8.1 Hz, 1H), 4.96 (dd, J = 13.2, 5.1 Hz, 1H), 4.30 - 4.09 (m, 5H), 3.39 (brs. 4H), 3.32 - 3.26 (m, 2H), 3.20 (brs, 4H), 2.90 -2.78 (m, 1H), 2.75 - 2.66 (m, 3H), 2.52 (d, J = 16.9 Hz, 1H), 2.35 - 2.21 (m, 1H), 1.91 - 1.87 (m, 1H). LCMS (ESI) calcd. for C28H33FN7O4+ [M+H]+: 550.26, found, 550.3.

[0327] Example 28: Preparation of compound GT-06865

[0328] With reference to the method of Scheme 4, the target compound GT-06865 was obtained (white solid, 35 mg, yield 53%). 1H NMR (400 MHz, DMSO-d6) 5 10.87 (s, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.22 (d, J = 8.9 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 6.90 (s, 1H), 6.82 (d, J = 8.3 Hz, 1H), 4.96 (dd, J = 13.3, 5.1 Hz, 1H), 4.27 - 4.01 (m, 5H), 3.33 - 3.23 (m, 6H), 3.12 (brs, 4H), 2.90 -2.77 (m, 1H), 2.76 - 2.60 (m, 3H), 2.52 (d, J = 16.8 Hz, 1H), 2.33 - 2.24 (m, 1H), 1.97 - 1.87 (m, 1H). LCMS (ESI) calcd. for C28H33ClN7O4+ [M+H]+: 566.23, found, 566.2.

[0329] Example 29: Preparation of compound GT-06866

[0330] With reference to the method of Scheme 4, the target compound GT-06866 was obtained (white solid, 36 mg, yield 51%). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 7.47 (d, J = 8.3 Hz, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 7.00 (s, 1H), 6.91 (d, J = 8.0 Hz, 1H), 5.03 (dd, J = 13.2, 5.0 Hz, 1H), 4.34 - 4.20 (m, 5H), 3.36 (brs, 6H), 3.20 (brs, 4H), 2.99 - 2.88 (m, 1H), 2.86 - 2.71 (m, 3H), 2.59 (d, J = 17.5 Hz, 1H), 2.41 - 2.33 (m, 1H), 1.98 - 1.90 (m, 1H). LCMS (ESI) calcd. for C28H33BrN7O4+ [M+H]+: 610.18, found, 610.2.

[0331] Example 30: Preparation of compound GT-06867

[0332] With reference to the method of Scheme 4, the target compound GT-06867 was obtained (white solid, 25 mg, yield 38%). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 7.46 (d, J = 8.3 Hz, 1H), 7.14 - 7.08 (m, 1H), 7.04 - 6.98 (m, 2H), 6.90 - 6.86 (m, 2H), 5.03 (dd, J = 13.3, 5.1 Hz, 1H), 4.37 - 4.19 (m, 5H), 3.35 (brs, 6H), 3.06 (brs, 4H), 2.97 - 2.85 (m, 1H), 2.81 - 2.72 (m, 3H), 2.59 (d, J = 16.6 Hz, 1H), 2.39 - 2.32 (m, 1H), 1.99 - 1.90 (m, 1H). LCMS (ESI) calcd. for C28H32F2N7O4+ [M+H]+: 568.25, found, 568.3.

[0333] Example 31: Preparation of compound GT-06868 (white solid, 15 mg, yield 24%). 1H NMR (400 MHz, DMSO-d6) 5 10.86 (s, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.22 (dd, J = 8.4, 5.7 Hz, 2H), 7.04 (t, J = 8.8 Hz, 2H), 6.86 (s, 1H), 6.78 (d, J = 8.4 Hz, 1H), 4.96 (dd, J = 13.3, 5.0 Hz, 1H), 4.24 (d, J = 16.8 Hz, 1H), 4.10 (d, J = 16.9 Hz, 1H), 3.65 (d, J = 12.7 Hz, 2H), 3.27 - 3.15 (m, 5H), 2.90 - 2.72 (m, 4H), 2.69 - 2.61 (m, 4H), 2.52 (d, J = 16.6 Hz, 1H), 2.33 - 2.20 (m, 1H), 1.93 - 1.82 (m, 1H), 1.70 - 1.67 (m, 2H), 1.54 - 1.45 (m, 2H). LCMS (ESI) calcd. for C29H34FN6O4+ [M+H]+: 549.26, found, 549.3.

[0335] Example 32: Preparation of compound GT-06869

[0336] With reference to the method of Scheme 4, the target compound GT-06869 was obtained (white solid, 18 mg, yield 26%). 1H NMR (400 MHz, DMSO-d6) 5 10.86 (s, 1H), 7.44 (dd, J = 7.7, 1.6 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.35 - 7.26 (m, 2H), 6.86 (s, 1H), 6.78 (d, J = 8.1 Hz, 1H), 4.96 (dd, J = 13.2, 5.0 Hz, 1H), 4.24 (d, J = 16.9 Hz, 1H), 4.10 (d, J = 16.9 Hz, 1H), 3.68 (d, J = 13.2 Hz, 2H), 3.27 - 3.19 (m, 5H), 3.11 (t, J = 12.0 Hz, 2H), 2.86 - 2.78 (m, 3H), 2.80 - 2.62 (m, 3H), 2.52 (d, J = 16.7 Hz, 1H), 2.32 - 2.22 (m, 1H), 1.91 - 1.84 (m, 1H), 1.72 - 1.69 (m, 2H), 1.57 - 1.49 (m, 2H). LCMS (ESI) calcd. for C29H33Cl2N6O4+ [M+H]+: 599.19, found, 599.2.

[0337] Example 33: Preparation of compound GT-06870

[0338] With reference to the method of Scheme 4, the target compound GT-06870 was obtained (white solid, 19 mg, yield 28%). 1H NMR (400 MHz, DMSO-d6) 5 10.86 (s, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.34 - 7.25 (m, 1H), 7.24 - 7.15 (m, 2H), 6.86 (s, 1H), 6.78 (d, J = 8.3 Hz, 1H), 4.95 (dd, J = 13.3, 5.1 Hz, 1H), 4.24 (d, J = 17.0 Hz, 1H), 4.10 (d, J = 17.0 Hz, 1H), 3.68 (d, J = 13.1 Hz, 2H), 3.35 - 3.14 (m, 5H), 3.07 (t, J = 12.0 Hz, 1H), 2.87 - 2.77 (m, 3H), 2.72 - 2.61 (m, 3H), 2.51 (d, J = 16.6 Hz, 1H), 2.32 - 2.22 (m, 1H), 1.92 - 1.86 (m, 1H), 1.71 - 1.68 (m, 2H), 1.58 - 1.50 (m, 2H). LCMS (ESI) calcd. for C29H33ClFN6O4+ [M+H]+: 583.22, found, 583.3.

[0339] Example 34: Preparation of compound GT-06871

[0340] With reference to the method of Scheme 4, the target compound GT-06871 was obtained (white solid, 22 mg, yield 33%). 1H NMR (400 MHz, DMSO-d6) 5 10.86 (s, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.23 - 7.18 (m, 1H), 7.14 - 7.08 (m, 2H), 6.86 (s, 1H), 6.78 (d, J = 8.3 Hz, 1H), 4.96 (dd, J = 13.3, 5.1 Hz, 1H), 4.24 (d, J = 16.9 Hz, 1H), 4.10 (d, J = 16.9 Hz, 1H), 3.66 (d, J = 12.9 Hz, 2H), 3.25 - 3.16 (m, 4H), 3.00 - 2.95 (m, 1H), 2.88 - 2.78 (m, 4H), 2.69 - 2.61 (m, 3H), 2.52 (d, J = 17.0 Hz, 1H), 2.32 - 2.22 (m, 1H), 1.93 - 1.86 (m, 1H), 1.73 - 1.66 (m, 2H), 1.63 - 1.54 (m, 2H). LCMS (ESI) calcd. for C29H33F2N6O4+ [M+H]+: 567.25, found, 567.3.

[0341] Example 35: Preparation of compound GT-06436

[0342] With reference to the method of Scheme 2, the target compound GT-06436 was obtained (pale yellow solid, 43 mg, yield 64 %). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 9.37 (s, 1H), 8.98 (s, 1H), 8.21 (dd, J = 7.9, 1.6 Hz, 2H), 7.67 - 7.55 (m, 4H), 7.25 (s, 1H), 7.06 (s, 1H), 5.06 (dd, J = 12.9, 5.3 Hz, 1H), 4.65 (d, J = 28.9 Hz, 2H), 3.51 (d, J = 33.9 Hz, 4H), 3.38 (s, 1H), 3.10 (d, J = 31.6 Hz, 4H), 2.88 (dd, J = 10.1, 7.0 Hz, 1H), 2.59 (d, J = 17.2 Hz, 1H), 2.54 (d, J = 4.5 Hz, 1H), 2.09 - 1.95 (m, 1H). LCMS (ESI) calcd. for C28H28N7O4+ [M+H]+: 526.22, found, 526.2.

[0343] Example 36: Preparation of compound GT-06437

[0344] With reference to the method of Scheme 2, the target compound GT-06437 was obtained (pale yellow solid, 37 mg, yield 53 %). 1H NMR (400 MHz, DMSO-d6) 8 11.09 (s, 1H), 10.94 (s, 1H), 9.37 (s, 1H), 8.97 (s, 1H), 8.21 (dd, J = 7.9, 1.6 Hz, 2H), 7.66 (d, J = 10.3 Hz, 1H), 7.58 (d, J = 7.4 Hz, 3H), 5.08 (dd, J = 12.8, 5.4 Hz, 1H), 4.65 (d, J = 30.2 Hz, 2H), 3.55 (s, 6H), 3.14 (s, 4H), 2.99 - 2.80 (m, 1H), 2.59 (d, J = 18.0 Hz, 1H), 2.09 - 1.96 (m, 1H). LCMS (ESI) calcd. for C28H27FN7O4+ [M+H]+: 544.21, found, 544.3.

[0345] Example 37: Preparation of compound GT-06438

[0346] With reference to the method of Scheme 2, the target compound GT-06438 was obtained (gray solid, 42 mg, yield 62 %). 1H NMR (400 MHz, DMSO-d6) 8 11.03 (d, J = 59.2 Hz, 2H), 9.37 (d, J = 1.3 Hz, 1H), 8.98 (d, J = 1.1 Hz, 1H), 8.22 (dd, J = 7.9, 1.6 Hz, 2H), 7.68 - 7.50 (m, 3H), 6.77 - 6.53 (m, 2H), 4.99 (dd, J = 13.3, 5.0 Hz, 1H), 4.60 (s, 2H), 4.25 (dd, J = 55.3, 17.3 Hz, 2H), 3.60 (dd, J = 20.2, 16.2 Hz, 5H), 3.09 (dd, J = 29.4, 21.6 Hz, 4H), 2.95 - 2.85 (m, 1H), 2.59 (d, J = 16.9 Hz, 1H), 2.33 (tt, J = 13.3, 6.8 Hz, 1H), 2.04 - 1.88 (m, 1H). LCMS (ESI) C28H29FN7O3+ [M+H]+: 530.23, found, 530.3.

[0347] Example 38: Preparation of compound GT-06439

[0348] With reference to the method of Scheme 2, the target compound GT-06439 was obtained (orange solid, 42 mg, yield 64 %). 1H NMR (400 MHz, DMSO-d6) 8 10.98 (d, J = 32.6 Hz, 2H), 9.38 (d, J = 1.4 Hz, 1H), 8.98 (d, J = 1.4 Hz, 1H), 8.22 (dd, J = 7.9, 1.7 Hz, 2H), 7.62 - 7.55 (m, 3H), 7.47 (d, J = 8.3 Hz, 1H), 7.01 - 6.83 (m, 2H), 5.04 (dd, J = 13.3, 5.1 Hz, 1H), 4.62 (s, 2H), 4.24 (dd, J = 52.7, 17.0 Hz, 2H), 3.57 (d, J = 11.5 Hz, 3H), 3.13 (d, J = 11.2 Hz, 2H), 2.92 (ddd, J = 17.4, 16.5, 9.6 Hz, 3H), 2.59 (d, J = 16.6 Hz, 1H), 2.35 (dd, J = 12.9, 4.4 Hz, 1H), 2.08 - 1.89 (m, 1H). LCMS (ESI) calcd. for C28H30N7O3+ [M+H]+: 512.24, found, 512.3.

[0349] Example 39: Preparation of compound GT-06440

[0350] With reference to the method of Scheme 2, the target compound GT-06440 was obtained (gray solid, 31 mg, yield 46 %). 1H NMR (400 MHz, DMSO-d6) 5 10.97 (s, 2H), 9.38 (d, J = 1.4 Hz, 1H), 8.97 (d, J = 1.4 Hz, 1H), 8.22 (dd, J = 7.9, 1.7 Hz, 2H), 7.62 - 7.54 (m, 3H), 7.43 (d, J = 8.2 Hz, 1H), 7.32 (t, J = 7.7 Hz, 1H), 5.05 (dd, J = 13.3, 5.1 Hz, 1H), 4.61 (s, 2H), 4.46 (d, J = 16.8 Hz, 1H), 4.28 (d, J = 16.8 Hz, 1H), 3.56 (s, 2H), 3.42 (s, 3H), 3.11 (s, 4H), 2.97 - 2.85 (m, 1H), 2.59 (d, J = 17.2 Hz, 1H), 2.40 (qd, J = 13.5, 4.5 Hz, 1H), 2.03 - 1.92 (m, 1H). LCMS (ESI) calcd. for C28H29FN7O3+ [M+H]+: 530.23, found, 530.3.

[0351] Example 40: Preparation of compound GT-06441

[0352] With reference to the method of Scheme 3, the target compound GT-06441 was obtained (pale yellow solid, 38 mg, yield 48 %). 1H NMR (400 MHz, DMSO-d6) 5 11.06 (s, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.57 - 7.52 (m, 3H), 7.52 - 7.49 (m, 1H), 7.45 (dd, J = 13.4, 8.4 Hz, 3H), 7.39 (d, J = 6.4 Hz, 1H), 7.15 (s, 1H), 7.02 (d, J = 7.7 Hz, 1H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 3.40 (s, 4H), 3.21 (s, 2H), 2.94 - 2.78 (m, 2H), 2.58 (d, J = 18.1 Hz, 3H), 2.47 (dd, J = 9.5, 4.5 Hz, 1H), 2.04 -1.94 (m, 1H). LCMS (ESI) calcd. for C30H28ClFN5O4+ [M+H]+: 572.18, found, 572.2.

[0353] Example 41: Preparation of compound GT-06442

[0354] With reference to the method of Scheme 3, the target compound GT-06442 was obtained (pale yellow solid, 41 mg, yield 50 %). 1H NMR (400 MHz, DMSO-d6) 5 11.08 (s, 1H), 8.12 (s, 1H), 7.62 (d, J = 10.3 Hz, 1H), 7.55 (dd, J = 7.2, 5.4 Hz, 3H), 7.45 (dd, J = 18.9, 7.6 Hz, 4H), 7.39 - 7.35 (m, 1H), 5.06 (dd, J = 12.8, 5.4 Hz, 1H), 3.35 (s, 3H), 3.27 (d, J = 6.9 Hz, 1H), 2.88 (ddd, J = 16.8, 13.8, 5.4 Hz, 2H), 2.74 (s, 1H), 2.65 - 2.51 (m, 4H), 2.50 - 2.44 (m, 1H), 2.05 - 1.95 (m, 1H). LCMS (ESI) calcd. for C30H26ClFN5O5+ [M+H]+: 590.16, found, 590.2.

[0355] Example 42: Preparation of compound GT-06443

[0356] With reference to the method of Scheme 3, the target compound GT-06443 was obtained (white solid, 44 mg, yield 55 %). 1H NMR (400 MHz, DMSO-d6) 5 10.86 (s, 1H), 7.47 (dt, J = 7.4, 3.1 Hz, 3H), 7.44 - 7.33 (m, 4H), 7.31 (d, J = 6.5 Hz, 1H), 6.59 (s, 1H), 6.45 (d, J = 12.4 Hz, 1H), 4.90 (dd, J = 13.3, 5.1 Hz, 1H), 4.22 (d, J = 17.2 Hz, 1H), 4.07 (d, J = 17.2 Hz, 1H), 3.31 (s, 4H), 3.22 (s, 1H), 3.10 (s, 1H), 2.89 - 2.70 (m, 2H), 2.50 (d, J = 16.5 Hz, 2H), 2.40 - 2.15 (m, 2H), 1.91 - 1.81 (m, 1H). LCMS (ESI) calcd. for C3oH2sClFN5O4+ [M+H]+: 576.18, found, 576.2.

[0357] Example 43: Preparation of compound GT-06444

[0358] With reference to the method of Scheme 3, the target compound GT-06444 was obtained (white solid, 36 mg, yield 47 %). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 7.57 - 7.52 (m, 3H), 7.52 - 7.40 (m, 5H), 7.40 - 7.36 (m, 1H), 6.89 (s, 1H), 6.81 (d, J = 8.3 Hz, 1H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.21 (dd, J = 54.5, 16.9 Hz, 2H), 3.48 (s, 2H), 3.18 (s, 1H), 2.89 (ddd, J = 18.7, 13.5, 5.2 Hz, 2H), 2.68 (s, 1H), 2.58 (d, J = 16.9 Hz, 2H), 2.48 - 2.26 (m, 2H), 1.99 - 1.90 (m, 1H). LCMS (ESI) calcd. for C30H29ClN5O4+ [M+H]+: 558.19, found, 558.2.

[0359] Example 44: Preparation of compound GT-06445

[0360] With reference to the method of Scheme 3, the target compound GT-06445 was obtained (white solid, 32 mg, yield 40 %). 1H NMR (400 MHz, DMSO-d6) 5 10.88 (s, 1H), 7.50 - 7.45 (m, 3H), 7.43 - 7.38 (m, 2H), 7.38 - 7.33 (m, 2H), 7.32 - 7.28 (m, 2H), 7.17 (t, J = 7.7 Hz, 1H), 4.96 (dd, J = 13.3, 5.0 Hz, 1H), 4.37 (d, J = 16.7 Hz, 1H), 4.19 (d, J = 16.7 Hz, 1H), 3.13 (s, 2H), 2.93 - 2.74 (m, 2H), 2.73 - 2.56 (m, 2H), 2.51 (d, J = 16.4 Hz, 2H), 2.41 - 2.24 (m, 2H), 1.93 - 1.82 (m, 1H). LCMS (ESI) calcd. for C30H28ClFN5O4+ [M+H]+: 576.18, found, 576.2.

[0361] Example 45: Preparation of compound GT-06446

[0362] With reference to the method of Scheme 2, the target compound GT-06446 was obtained (white solid, 23 mg, yield 33 %). 1H NMR (400 MHz, DMSO-d6) 5 10.96 (s, 2H), 9.37 (d, J = 1.3 Hz, 1H), 8.98 (d, J = 1.2 Hz, 1H), 8.22 (dd, J = 7.9, 1.6 Hz, 2H), 7.68 - 7.49 (m, 3H), 7.33 (dd, J = 29.4, 8.9 Hz, 2H), 5.05 (dd, J = 13.3, 5.1 Hz, 1H), 4.61 (s, 2H), 4.26 (dd, J = 50.0, 16.9 Hz, 2H), 3.56 (s, 2H), 3.40 (s, 3H), 3.13 (s, 4H), 2.89 (d, J = 13.1 Hz, 1H), 2.59 (d, J = 16.5 Hz, 1H), 2.37 (dd, J = 13.1, 4.4 Hz, 1H), 2.03 - 1.90 (m, 1H). LCMS (ESI) calcd. for C28H29FN7O3+ [M+H]+: 530.23, found, 530.3.

[0363] Example 46: Preparation of compound GT-06447

[0364] With reference to the method of Scheme 3, the target compound GT-06447 was obtained (white solid, 26 mg, yield 33 %). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 7.58 - 7.52 (m, 3H), 7.49 (dd, J = 12.6, 6.8 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 7.37 (d, J = 6.7 Hz, 1H), 7.34 (s, 1H), 7.23 (d, J = 7.2 Hz, 1H), 5.03 (dd, J = 13.2, 5.1 Hz, 1H), 4.24 (dd, J = 53.3, 17.0 Hz, 2H), 3.38 (s, 2H), 3.21 (s, 2H), 3.01 - 2.81 (m, 2H), 2.64 (t, J = 33.9 Hz, 4H), 2.33 (dd, J = 13.1, 4.5 Hz, 2H), 2.01 - 1.89 (m, 1H). LCMS (ESI) calcd. for C3oH2sClFN5O4+ [M+H]+: 576.18, found, 576.3.

[0365] Example 47: Preparation of compound GT-06460

[0366] With reference to the method of Scheme 3, the target compound GT-06460 was obtained (white solid, 44 mg, yield 58 %). 1H NMR (400 MHz, DMSO-d6) 5 11.06 (s, 1H), 7.96 (s, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.27 (d, J = 5.6 Hz, 2H), 7.18 (t, J = 8.9 Hz, 2H), 7.12 (s, 1H), 7.00 (d, J = 7.5 Hz, 1H), 5.03 (dd, J = 12.8, 5.4 Hz, 1H), 4.16 (s, 1H), 3.43 (dd, J = 28.9, 7.6 Hz, 2H), 3.32 (t, J = 6.5 Hz, 2H), 2.85 (ddd, J = 74.1, 39.8, 33.0 Hz, 3H), 2.57 (d, J = 17.2 Hz, 2H), 2.41 (dd, J = 34.8, 11.0 Hz, 3H), 2.11 (d, J = 17.9 Hz, 1H), 2.02 - 1.87 (m, 2H), 1.46 (d, J = 9.9 Hz, 2H), 0.99 (d, J = 13.1 Hz, 6H). LCMS (ESI) calcd. for C32H35FN5O5+ [M+H]+: 588.26, found, 588.3.

[0367] Example 48: Preparation of compound GT-06461

[0368] With reference to the method of Scheme 3, the target compound GT-06461 was obtained (white solid, 48 mg, yield 62 %). 1H NMR (400 MHz, DMSO-d6) 5 11.00 (s, 1H), 8.02 (s, 1H), 7.53 (d, J = 10.3 Hz, 1H), 7.36 (d, J = 7.0 Hz, 1H), 7.23 - 7.15 (m, 2H), 7.09 (t, J = 8.9 Hz, 2H), 4.98 (dd, J = 12.7, 5.4 Hz, 1H), 4.11 (s, 1H), 3.64 - 3.29 (m, 2H), 3.21 (d, J = 25.2 Hz, 1H), 2.93 - 2.58 (m, 3H), 2.50 (d, J = 19.5 Hz, 3H), 2.41 - 2.20 (m, 3H), 2.06 (s, 1H), 1.96 - 1.78 (m, 2H), 1.39 (d, J = 9.8 Hz, 2H), 0.92 (d, J = 10.6 Hz, 6H). LCMS (ESI) calcd. for C32H34F2N5O5+ [M+H]+: 606.25, found, 606.3.

[0369] Example 49: Preparation of compound GT-06462

[0370] With reference to the method of Scheme 3, the target compound GT-06462 was obtained (white solid, 40 mg, yield 54 %). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.27 (dd, J = 8.7, 5.6 Hz, 2H), 7.17 (t, J = 8.9 Hz, 3H), 6.86 (s, 1H), 6.79 (d, J = 8.3 Hz, 1H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.20 (dd, J = 54.5, 16.9 Hz, 2H), 3.32 - 3.01 (m, 3H), 2.95 - 2.67 (m, 2H), 2.58 (d, J = 16.8 Hz, 2H), 2.33 (ddd, J = 23.6, 17.6, 12.0 Hz, 5H), 2.17 - 1.83 (m, 4H), 1.51 - 1.36 (m, 2H), 0.99 (d, J = 13.0 Hz, 6H). LCMS (ESI) calcd. for C32H37FN5O4+ [M+H]+: 574.28, found, 574.3 .

[0371] Example 50: Preparation of compound GT-06463

[0372] With reference to the method of Scheme 3, the target compound GT-06463 was obtained (white solid, 35 mg, yield 46 %). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.33 - 7.23 (m, 3H), 7.18 (dd, J = 17.3, 8.4 Hz, 3H), 5.03 (dd, J = 13.3, 5.0 Hz, 1H), 4.43 (d, J = 16.7 Hz, 1H), 4.25 (d, J = 16.7 Hz, 1H), 3.37 (s, 3H), 3.02 - 2.83 (m, 2H), 2.58 (d, J = 13.4 Hz, 3H), 2.46 - 2.28 (m, 4H), 2.00 (t, J = 42.5 Hz, 4H), 1.54 - 1.40 (m, 2H), 0.99 (d, J = 11.2 Hz, 6H). LCMS (ESI) calcd. for C32H36F2N5O4+ [M+H]+: 592.27, found, 592.3.

[0373] Example 51: Preparation of compound GT-06464

[0374] With reference to the method of Scheme 3, the target compound GT-06464 was obtained (white solid, 46 mg, yield 61 %). 1H NMR (400 MHz, DMSO-d6) 8 10.94 (s, 1H), 7.55 (s, 1H), 7.33 - 7.23 (m, 2H), 7.17 (t, J = 8.9 Hz, 2H), 6.64 (s, 1H), 6.50 (d, J = 12.3 Hz, 1H), 4.97 (dd, J = 13.3, 5.1 Hz, 1H), 4.28 (d, J = 17.2 Hz, 1H), 4.14 (d, J = 17.2 Hz, 1H), 3.35 - 3.25 (m, 3H), 2.98 - 2.72 (m, 2H), 2.63 (dd, J = 45.2, 12.5 Hz, 3H), 2.47 - 2.25 (m, 4H), 1.97 (dd, J = 46.3, 41.1 Hz, 4H), 1.53 - 1.39 (m, 2H), 0.99 (d, J = 13.3 Hz, 6H). LCMS (ESI) calcd. for C32H36F2N5O4+ [M+H]+: 592.27, found, 592.3.

[0375] Example 52: Preparation of compound GT-06465

[0376] With reference to the method of Scheme 3, the target compound GT-06465 was obtained (white solid, 14 mg, yield 41 %). 1H NMR (400 MHz, DMSO-d6) 8 10.99 (s, 1H), 7.93 (s, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.1 Hz, 2H), 7.05 (s, 1H), 6.93 (d, J = 8.2 Hz, 1H), 4.96 (dd, J = 12.8, 5.3 Hz, 1H), 4.11 (s, 1H), 2.86 - 2.58 (m, 3H), 2.58 - 2.46 (m, 3H), 2.39 - 2.23 (m, 3H), 2.11 - 1.78 (m, 4H), 1.38 (s, 2H), 0.92 (d, J = 10.3 Hz, 6H). LCMS (ESI) calcd. for C32H35ClN5O5+ [M+H]+: 604.23, found, 604.3.

[0377] Example 53: Preparation of compound GT-06466

[0378] With reference to the method of Scheme 3, the target compound GT-06466 was obtained (white solid, 16 mg, yield 46 %). 1H NMR (400 MHz, DMSO-d6) 8 11.01 (s, 1H), 8.01 (s, 1H), 7.54 (d, J = 10.3 Hz, 1H), 7.41 - 7.31 (m, 3H), 7.17 (d, J = 8.3 Hz, 2H), 4.99 (dd, J = 12.8, 5.4 Hz, 1H), 4.13 (s, 1H), 3.56 - 3.30 (m, 2H), 2.92 - 2.61 (m, 3H), 2.53 (dd, J = 32.1, 16.3 Hz, 3H), 2.31 (dd, J = 55.2, 10.1 Hz, 3H), 2.19 - 1.75 (m, 4H), 1.38 (s, 2H), 0.92 (d, J = 3.9 Hz, 6H). LCMS (ESI) calcd. for C32H34ClFN5O5+ [M+H]+: 622.22, found, 622.3.

[0379] Example 54: Preparation of compound GT-06467

[0380] With reference to the method of Scheme 3, the target compound GT-06467 was obtained (white solid, 8 mg, yield 22 %). 1H NMR (400 MHz, DMSO-d6) 8 10.88 (s, 1H), 7.31 (dd, J = 15.6, 8.4 Hz, 3H), 7.23 - 7.07 (m, 4H), 4.96 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 16.8 Hz, 1H), 4.18 (d, J = 16.8 Hz, 1H), 3.32 (s, 3H), 2.95 - 2.69 (m, 2H), 2.54 (t, J = 22.2 Hz, 4H), 2.41 - 2.17 (m, 4H), 2.10 - 1.82 (m, 3H), 1.39 (d, J = 10.8 Hz, 2H), 0.92 (d, J = 8.0 Hz, 6H). LCMS (ESI) calcd. for C32H36ClFN5O4 + [M+H]+: 608.24, found, 608.3.

[0381] Example 55: Preparation of compound GT-06468

[0382] With reference to the method of Scheme 3, the target compound GT-06468 was obtained (white solid, 15 mg, yield 44 %). 1H NMR (400 MHz, DMSO-d6) 8 10.87 (s, 1H), 7.51 (s, 1H), 7.33 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 6.58 (s, 1H), 6.44 (d, J = 12.3 Hz, 1H), 4.90 (dd, J = 13.3, 5.1 Hz, 1H), 4.21 (d, J = 17.2 Hz, 1H), 4.07 (d, J = 17.2 Hz, 1H), 3.29 - 2.97 (m, 3H), 2.88 - 2.67 (m, 2H), 2.56 (dd, J = 44.4, 12.2 Hz, 3H), 2.38 - 2.18 (m, 4H), 1.91 (dd, J = 44.6, 39.7 Hz, 4H), 1.39 (d, J = 9.8 Hz, 2H), 0.92 (d, J = 10.8 Hz, 6H). LCMS (ESI) calcd. for C32H36ClFN5O4 + [M+H]+: 608.24, found, 608.3.

[0383] Example 56: Preparation of compound GT-06469

[0384] With reference to the method of Scheme 1, the target compound GT-06469 was obtained (yellow solid, 10 mg, yield 13 %). 1H NMR (400 MHz, DMSO-d6) 8 10.99 (s, 1H), 9.87 (s, 1H), 8.32 (s, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.40 (d, J = 8.1 Hz, 2H), 7.15 - 7.07 (m, 3H), 6.95 (d, J = 6.6 Hz, 1H), 4.97 (dd, J = 12.7, 5.2 Hz, 1H), 3.55 (s, 2H), 3.05 - 2.74 (m, 8H), 2.62 - 2.46 (m, 2H), 2.27 (s, 2H), 2.05 - 1.85 (m, 4H), 1.41 (s, 2H), 0.90 (s, 6H). LCMS (ESI) calcd. for C32H37ClN5O4+ [M+H]+: 590.25, found, 590.3.

[0385] Example 57: Preparation of compound GT-06470

[0386] With reference to the method of Scheme 1, the target compound GT-06470 was obtained (yellow solid, 18 mg, yield 28 %). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 9.82 (s, 1H), 8.42 (s, 1H), 7.64 (d, J = 10.3 Hz, 1H), 7.50 (dd, J = 17.3, 7.6 Hz, 3H), 7.16 (d, J = 8.3 Hz, 2H), 5.06 (dd, J = 12.8, 5.4 Hz, 1H), 3.63 (s, 2H), 3.17 (d, J = 11.5 Hz, 3H), 3.12 - 2.79 (m, 6H), 2.56 (dd, J = 15.6, 12.3 Hz, 2H), 2.33 (s, 2H), 2.06 - 1.98 (m, 3H), 1.49 (t, J = 5.9 Hz, 2H), 0.97 (s, 6H). LCMS (ESI) calcd. for C32H36ClFN5O4+ [M+H]+: 608.24, found, 608.3.

[0387] Example 58: Preparation of compound GT-06471

[0388] With reference to the method of Scheme 1, the target compound GT-06471 was obtained (yellow solid, 13 mg, yield 19 %). 1H NMR (400 MHz, DMSO-d6) 8 10.96 (s, 1H), 9.70 (s, 1H), 7.73 (s, 1H), 7.48 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.2 Hz, 1H), 7.27 (t, J = 7.8 Hz, 1H), 7.17 (d, J = 8.3 Hz, 2H), 5.04 (dd, J = 13.3, 5.1 Hz, 1H), 4.45 (d, J = 16.8 Hz, 1H), 4.27 (d, J = 16.8 Hz, 1H), 3.61 (s, 2H), 3.31 - 3.25 (m, 1H), 3.09 (d, J = 12.2 Hz, 2H), 2.89 (dd, J = 22.5, 8.7 Hz, 5H), 2.70 - 2.52 (m, 2H), 2.45 - 2.28 (m, 3H), 2.06 - 1.90 (m, 3H), 1.49 (t, J = 6.0 Hz, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H38ClFN5O3+ [M+H]+: 594.26, found, 594.3.

[0389] Example 59: Preparation of compound GT-06472

[0390] With reference to the method of Scheme 1, the target compound GT-06472 was obtained (yellow solid, 13 mg, yield 20 %). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 9.94 (s, 1H), 7.99 (s, 1H), 7.46 (t, J = 9.6 Hz, 2H), 7.16 (d, J = 8.3 Hz, 2H), 6.71 - 6.54 (m, 2H), 4.98 (dd, J = 13.3, 5.1 Hz, 1H), 4.29 (d, J = 17.1 Hz, 1H), 4.15 (d, J = 17.1 Hz, 1H), 3.61 (s, 2H), 3.28 - 3.23 (m, 1H), 3.08 - 2.84 (m, 7H), 2.63 - 2.53 (m, 2H), 2.32 (d, J = 12.6 Hz, 3H), 2.05 (s, 2H), 1.99 -1.91 (m, 1H), 1.49 (t, J = 6.2 Hz, 2H), 0.97 (s, 6H). LCMS (ESI) calcd. for C32H38ClFN5O3+ [M+H]+: 594.26, found, 594.3.

[0391] Example 60: Preparation of compound GT-06473

[0392] With reference to the method of Scheme 1, the target compound GT-06473 was obtained (yellow solid, 14 mg, yield 21 %). 1H NMR (400 MHz, DMSO-d6) 5 11.08 (d, J = 8.3 Hz, 1H), 9.92 (s, 1H), 8.38 (s, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.27 - 6.94 (m, 6H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 3.70 - 3.52 (m, 2H), 3.37 (s, 1H), 3.32 (s, 2H), 3.12 - 2.83 (m, 6H), 2.56 (dd, J = 17.4, 12.2 Hz, 2H), 2.34 (s, 2H), 2.09 - 1.95 (m, 3H), 1.49 (t, J = 6.4 Hz, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H37FN5O4+ [M+H]+: 574.28, found, 574.3.

[0393] Example 61: Preparation of compound GT-06474

[0394] With reference to the method of Scheme 1, the target compound GT-06474 was obtained (yellow solid, 14 mg, yield 20 %). 1H NMR (400 MHz, DMSO-d6) 5 11.08 (s, 1H), 9.69 (s, 1H), 8.41 (s, 1H), 7.64 (d, J = 10.3 Hz, 1H), 7.52 (d, J = 6.8 Hz, 1H), 7.27 - 7.12 (m, 4H), 5.06 (dd, J = 12.8, 5.4 Hz, 1H), 3.64 (s, 2H), 3.31 - 3.23 (m, 2H), 3.14 (d, J = 11.5 Hz, 2H), 3.08 - 2.82 (m, 5H), 2.68 - 2.53 (m, 2H), 2.31 (s, 2H), 2.08 - 1.96 (m, 3H), 1.48 (d, J = 6.1 Hz, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H36F2N5O4+ [M+H]+: 592.27, found, 592.3.

[0395] Example 62: Preparation of compound GT-06475

[0396] With reference to the method of Scheme 1, the target compound GT-06475 was obtained (yellow solid, 12 mg, yield 18 %). 1H NMR (400 MHz, DMSO-d6) 5 10.96 (s, 1H), 9.75 (s, 1H), 7.73 (s, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.22 (dt, J = 13.9, 8.6 Hz, 5H), 5.04 (dd, J = 13.3, 5.1 Hz, 1H), 4.45 (d, J = 16.9 Hz, 1H), 4.27 (d, J = 16.8 Hz, 1H), 3.61 (d, J = 3.8 Hz, 2H), 3.33 - 3.32 (m, 1H), 3.10 (t, J = 11.5 Hz, 2H), 2.92 (dd, J = 19.3, 11.8 Hz, 5H), 2.57 (dd, J = 17.7, 10.6 Hz, 2H), 2.45 - 2.28 (m, 3H), 2.06 (s, 2H), 2.00 - 1.91 (m, 1H), 1.49 (t, J = 6.1 Hz, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H38F2N5O3+ [M+H]+:  578.29, found, 578.3.

[0397] Example 63: Preparation of compound GT-06476

[0398] With reference to the method of Scheme 1, the target compound GT-06476 was obtained (yellow solid, 10 mg, yield 14 %). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 9.94 (s, 1H), 7.98 (s, 1H), 7.21 (dt, J = 14.0, 8.5 Hz, 4H), 6.74 - 6.51 (m, 2H), 4.98 (dd, J = 13.3, 5.0 Hz, 1H), 4.29 (d, J = 17.2 Hz, 1H), 4.15 (d, J = 17.2 Hz, 1H), 3.60 (s, 2H), 3.31 - 3.28 (m, 1H), 3.14 - 2.81 (m, 7H), 2.62 - 2.52 (m, 2H), 2.38 - 2.25 (m, 3H), 2.05 (s, 2H), 1.98 - 1.89 (m, 1H), 1.49 (t, J = 6.1 Hz, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H38F2N5O3+ [M+H]+: 578.29, found, 578.3.

[0399] Example 64: Preparation of compound GT-06536

[0400] With reference to the method of Scheme 1, the target compound GT-06536 was obtained (yellow solid, 14 mg, yield 20 %). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (d, J = 7.6 Hz, 1H), 9.85 (s, 1H), 7.60 (d, J = 19.5 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.25 (t, J = 8.8 Hz, 2H), 7.17 (dd, J = 8.4, 5.7 Hz, 2H), 6.90 (s, 1H), 6.84 (d, J = 8.7 Hz, 1H), 5.02 (dd, J = 13.2, 5.0 Hz, 1H), 4.21 (dd, J = 52.6, 16.8 Hz, 2H), 3.60 (s, 2H), 3.30 - 3.26 (m, 1H), 3.05 - 2.80 (m, 7H), 2.65 - 2.52 (m, 2H), 2.33 (s, 3H), 2.05 (s, 2H), 1.99 - 1.92 (m, 1H), 1.49 (t, J = 6.0 Hz, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H39FN5O3+ [M+H]+: 560.30, found, 560.4.

[0401] Example 65: Preparation of compound GT-06537

[0402] With reference to the method of Scheme 1, the target compound GT-06537 was obtained (yellow solid, 15 mg, yield 19 %). 1H NMR (400 MHz, DMSO-d6) 5 10.88 (s, 1H), 9.73 (s, 1H), 7.65 (s, 1H), 7.39 (t, J = 9.4 Hz, 2H), 7.27 (d, J = 10.7 Hz, 1H), 7.16 (d, J = 7.2 Hz, 1H), 7.08 (t, J = 9.1 Hz, 2H), 4.96 (dd, J = 13.3, 5.0 Hz, 1H), 4.15 (dd, J = 50.2, 16.9 Hz, 2H), 3.54 (s, 2H), 3.34 (s, 1H), 3.05 (s, 2H), 2.94 - 2.75 (m, 5H), 2.50 (dd, J = 16.8, 10.8 Hz, 2H), 2.29 (dd, J = 15.7, 11.4 Hz, 3H), 1.97 (s, 2H), 1.93 - 1.83 (m, 1H), 1.42 (t, J = 6.1 Hz, 2H), 0.90 (s, 6H). LCMS (ESI) calcd. for C32H38ClFN5O3+ [M+H]+: 594.26, found, 594.3.

[0403] Example 66: Preparation of compound GT-06538

[0404] With reference to the method of Scheme 1, the target compound GT-06538 was obtained (yellow solid, 18 mg, yield 21 %). 1H NMR (400 MHz, DMSO-d6) 5 10.88 (s, 1H), 9.62 (s, 1H), 7.64 (s, 1H), 7.28 (d, J = 10.7 Hz, 1H), 7.17 (dd, J = 10.0, 7.8 Hz, 3H), 7.10 (t, J = 7.0 Hz, 2H), 4.96 (dd, J = 13.2, 5.1 Hz, 1H), 4.15 (dd, J = 49.8, 16.9 Hz, 2H), 3.54 (s, 2H), 3.23 - 3.19 (m, 1H), 3.02 (s, 2H), 2.93 - 2.77 (m, 5H), 2.56 - 2.44 (m, 2H), 2.24 (d, J = 7.6 Hz, 2H), 1.98 (s, 2H), 1.93 - 1.84 (m, 1H), 1.42 (t, J = 6.2 Hz, 2H), 0.90 (s, 6H). LCMS (ESI) calcd. for C32H38F2N5O3 + [M+H]+: 578.29, found, 578.3.

[0405] Example 67: Preparation of compound GT-06539

[0406] With reference to the method of Scheme 3, the target compound GT-06539 was obtained (white solid, 10 mg, yield 14 %). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 10.7 Hz, 1H), 7.29 - 7.19 (m, 4H), 5.03 (dd, J = 13.3, 5.0 Hz, 1H), 4.23 (dd, J = 52.6, 17.0 Hz, 2H), 3.44 (s, 2H), 3.00 (s, 2H), 2.90 (dd, J = 11.1, 6.2 Hz, 1H), 2.59 (d, J = 15.6 Hz, 4H), 2.47 - 2.28 (m, 4H), 2.13 (s, 1H), 1.99 - 1.91 (m, 2H), 1.47 (d, J = 9.9 Hz, 2H), 0.99 (d, J = 8.2 Hz, 6H). LCMS (ESI) calcd. for C32H36ClFN5O4+ [M+H]+: 608.24, found, 608.3.

[0407] Example 68: Preparation of compound GT-06540

[0408] With reference to the method of Scheme 3, the target compound GT-06540 was obtained (white solid, 30 mg, yield 39 %). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 7.36 - 7.28 (m, 2H), 7.26 (dd, J = 8.5, 5.7 Hz, 2H), 7.18 (dd, J = 16.6, 7.8 Hz, 3H), 5.02 (dd, J = 13.2, 5.1 Hz, 1H), 4.22 (dd, J = 52.8, 16.9 Hz, 2H), 3.42 (s, 2H), 3.29 (d, J = 6.1 Hz, 2H), 2.92 - 2.84 (m, 1H), 2.58 (d, J = 16.8 Hz, 4H), 2.48 - 2.28 (m, 4H), 2.12 (s, 1H), 1.93 (d, J = 15.0 Hz, 2H), 1.46 (dd, J = 11.4, 5.8 Hz, 2H), 0.99 (d, J = 11.1 Hz, 6H). LCMS (ESI) calcd. for C32H36F2N5O4+ [M+H]+: 592.27, found, 592.3.

[0409] Example 69: Preparation of compound GT-06541

[0410] With reference to the method of Scheme 2, the target compound GT-06541 was obtained (white solid, 13 mg, yield 19 %). 1H NMR (400 MHz, DMSO-d6) 5 11.88 (s, 1H), 11.07 (s, 1H), 8.44 (s, 1H), 7.92 (s, 3H), 7.62 (d, J = 8.2 Hz, 1H), 7.27 (d, J = 35.7 Hz, 5H), 7.01 (s, 1H), 5.69 (s, 1H), 5.04 (dd, J = 12.7, 5.3 Hz, 1H), 3.32 - 3.04 (m, 7H), 2.89 (dd, J = 22.2, 9.2 Hz, 2H), 2.58 (d, J = 17.9 Hz, 2H), 2.06 - 1.88 (m, 1H). LCMS (ESI) calcd. for C30H28F2N5O4+ [M+H]+: 560.21, found, 560.2.

[0411] Example 70: Preparation of compound GT-06542

[0412] With reference to the method of Scheme 2, the target compound GT-06542 was obtained (white solid, 22 mg, yield 30 %). 1H NMR (400 MHz, DMSO-d6) 8 12.06 (s, 1H), 11.07 (s, 1H), 8.46 (s, 1H), 7.84 (d, J = 39.2 Hz, 3H), 7.65 - 7.47 (m, 5H), 7.22 (s, 1H), 7.02 (s, 1H), 5.69 (s, 1H), 5.05 (dd, J = 12.7, 5.4 Hz, 1H), 3.23 (s, 4H), 3.06 (s, 3H), 2.98 - 2.81 (m, 2H), 2.58 (d, J = 18.1 Hz, 2H), 2.06 - 1.94 (m, 1H). LCMS (ESI) calcd. for C30H28Cl2N5O4+ [M+H]+: 592.15, found, 592.2.

[0413] Example 71: Preparation of compound GT-06543

[0414] With reference to the method of Scheme 2, the target compound GT-06543 was obtained (white solid, 4 mg, yield 5 %). 1H NMR (400 MHz, DMSO-d6) 8 11.45 (s, 1H), 11.07 (s, 1H), 8.46 (s, 1H), 7.76 (d, J = 8.2 Hz, 4H), 7.63 (d, J = 8.2 Hz, 1H), 7.23 (d, J = 8.5 Hz, 1H), 7.01 (d, J = 8.3 Hz, 5H), 5.48 (d, J = 8.1 Hz, 1H), 5.05 (dd, J = 12.9, 5.2 Hz, 1H), 3.75 (s, 6H), 3.19 (d, J = 10.3 Hz, 4H), 3.10 (s, 3H), 2.97 - 2.78 (m, 2H), 2.68 - 2.54 (m, 2H), 2.03 - 1.94 (m, 1H). LCMS (ESI) calcd. for C32H34N5O6+ [M+H]+: 584.25, found, 584.3.

[0415] Example 72: Preparation of compound GT-06544

[0416] With reference to the method of Scheme 1, the target compound GT-06544 was obtained (yellow solid, 27 mg, yield 39 %). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 10.91 (s, 1H), 8.44 (s, 1H), 8.00 (s, 1H), 7.79 (d, J = 8.5 Hz, 3H), 7.64 (d, J = 8.3 Hz, 1H), 7.58 (t, J = 5.9 Hz, 4H), 7.24 (s, 1H), 7.04 (s, 1H), 5.05 (dd, J = 12.8, 5.3 Hz, 1H), 4.42 (s, 2H), 3.40 (s, 2H), 3.32 -3.19 (m, 2H), 3.13 (d, J = 10.8 Hz, 2H), 3.03 (s, 2H), 2.89 (dd, J = 15.6, 10.1 Hz, 1H), 2.60 (dd, J = 36.5, 18.6 Hz, 2H), 2.08 - 1.95 (m, 1H). LCMS (ESI) calcd. for C30H29ClN5O4+ [M+H]+: 558.19, found, 558.2.

[0417] Example 73: Preparation of compound GT-06545

[0418] With reference to the method of Scheme 1, the target compound GT-06545 was obtained (yellow solid, 24 mg, yield 35 %). 1H NMR (400 MHz, DMSO-d6) 8 11.09 (d, J = 8.4 Hz, 1H), 10.81 (s, 1H), 8.44 (s, 1H), 7.84 - 7.69 (m, 6H), 7.64 (d, J = 8.3 Hz, 1H), 7.55 (d, J = 8.6 Hz, 2H), 7.24 (s, 1H), 7.04 (s, 1H), 5.06 (dd, J = 12.9, 5.3 Hz, 1H), 4.40 (s, 2H), 3.14 (d, J = 11.4 Hz, 2H), 3.07 - 2.92 (m, 2H), 2.89 (dd, J = 15.6, 10.4 Hz, 1H), 2.65 - 2.52 (m, 2H), 2.10 - 1.91 (m, 1H). LCMS (ESI) calcd. for C30H29ClN5O4+ [M+H]+: 558.19, found, 558.2.

[0419] Example 74: Preparation of compound GT-06546

[0420] With reference to the method of Scheme 1, the target compound GT-06546 was obtained (yellow solid, 26 mg, yield 38 %). 1H NMR (400 MHz, DMSO-d6) 8 11.07 (s, 1H), 10.15 (s, 1H), 8.38 (s, 1H), 7.62 (t, J = 8.9 Hz, 1H), 7.28 (d, J = 7.3 Hz, 3H), 7.23 - 7.13 (m, 1H), 7.03 (s, 1H), 5.04 (dd, J = 12.7, 5.3 Hz, 1H), 4.36 (s, 2H), 3.84 (t, J = 5.3 Hz, 2H), 3.67 (s, 2H), 3.40 (s, 2H), 3.32 - 3.19 (m, 2H), 3.18 - 2.85 (m, 6H), 2.58 (d, J = 18.3 Hz, 2H), 2.38 (s, 1H), 2.04 - 1.96 (m, 1H). LCMS (ESI) calcd. for C29H31FN5O5+ [M+H]+: 548.23, found, 548.2.

[0421] Example 75: Preparation of compound GT-06547

[0422] With reference to the method of Scheme 1, the target compound GT-06547 was obtained (yellow solid, 26 mg, yield 36 %). 1H NMR (400 MHz, DMSO-d6) 8 11.00 (s, 1H), 10.00 (s, 1H), 8.30 (s, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.43 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H), 7.12 (s, 1H), 6.94 (d, J = 7.6 Hz, 1H), 4.97 (dd, J = 12.8, 5.4 Hz, 1H), 4.29 (s, 2H), 3.62 (s, 2H), 2.93 (s, 6H), 2.79 (dd, J = 16.7, 5.0 Hz, 2H), 2.51 (d, J = 18.3 Hz, 3H), 2.17 (s, 2H), 1.94 - 1.88 (m, 1H), 1.16 (s, 6H). LCMS (ESI) calcd. for C31H35ClN5O5+ [M+H]+: 592.23, found, 592.3.

[0423] Example 76: Preparation of compound GT-07057

[0424] With reference to the method of Scheme 3, the target compound GT-07057 was obtained (white solid, 29 mg, yield 43 %). 1H NMR (500 MHz, DMSO-d6) 8 11.08 (s, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.33 - 7.30 (m, 2H), 7.25 - 7.20 (m, 2H), 5.07 (dd, J = 12.8, 5.4 Hz, 1H), 4.24 - 3.90 (m, 6H), 2.92 - 2.84 (m, 1H), 2.65 - 2.55 (m, 4H), 2.27 (brs, 2H), 2.14 - 1.97 (m, 3H), 1.44 - 1.39 (m, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H35ClN5O5+ [M+H]+: 604.23, found, 604.3.

[0425] Example 77: Preparation of compound GT-07058

[0426] With reference to the method of Scheme 3, the target compound GT-07058 was obtained (white solid, 48 mg, yield 68 %). 1H NMR (500 MHz, DMSO-d6) 8 11.07 (s, 1H), 9.80 (d, J = 1.8 Hz, 1H), 8.81 (d, J = 1.8 Hz, 1H), 7.48 - 7.40 (m, 3H), 7.25 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 1.3 Hz, 1H), 6.21 (s, 1H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 2.94 - 2.79 (m, 1H), 2.59 - 2.56 (m, 1H), 2.48 - 2.46 (m, 1H), 2.35 (t, J = 6.2 Hz, 2H), 2.10 (s, 2H), 2.03 - 1.97 (m, 1H), 1.46 (t, J = 6.4 Hz, 2H), 1.02 (s, 6H). LCMS (ESI) calcd. for C28H28ClN4O5+ [M+H]+: 535.17, found, 535.2.

[0427] Example 78: Preparation of compound GT-07059

[0428] With reference to the method of Scheme 3, the target compound GT-07059 was obtained (white solid, 26 mg, yield 39 %). 1H NMR (500 MHz, DMSO-d6) 5 10.98 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.41 (d, J = 17.4 Hz, 1H), 4.29 (d, J = 17.4 Hz, 1H), 3.03 - 2.86 (m, 4H), 2.64 - 2.58 (m, 2H), 2.42 - 2.36 (m, 2H), 2.27 (s, 2H), 2.21 - 2.15 (m, 1H), 2.08 (d, J = 1.7 Hz, 2H), 2.04 - 1.94 (m, 1H), 1.80 (d, J = 12.5 Hz, 2H), 1.57 (s, 1H), 1.41 (t, J = 6.3 Hz, 2H), 1.35 (d, J = 9.6 Hz, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C34H40ClN4O4S+ [M+H]+: 635.25, found, 635.3.

[0429] Example 79: Preparation of compound GT-07066

[0430] With reference to the method of Scheme 7, the target compound GT-07066 was obtained (white solid, 26 mg, yield 38 %). 1H NMR (500 MHz, DMSO-d6) 5 10.94 (s, 1H), 8.70 (s, 1H), 7.50 (d, J = 8.5 Hz, 1H), 7.40 - 7.34 (m, 2H), 7.30 (d, J = 8.6 Hz, 1H), 7.26 - 7.19 (m, 1H), 7.08 - 6.99 (m, 2H), 5.04 (dd, J = 13.3, 5.1 Hz, 1H), 4.31 (d, J = 16.9 Hz, 1H), 4.19 (d, J = 16.9 Hz, 1H), 3.33 - 3.20 (m, 3H), 2.96 - 2.83 (m, 1H), 2.63 - 2.54 (m, 4H), 2.52 - 2.50 (m, 1H), 2.44 -2.31 (m, 2H), 2.27 (brs, 2H), 2.08 - 2.05(m, 2H), 2.01 - 1.89 (m, 1H), 1.43 - 1.35 (m, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C32H37ClN5O4+ [M+H]+: 590.25, found, 590.3.

[0431] Example 80: Preparation of compound GT-06911

[0432] With reference to the method of Scheme 2, the target compound GT-06911 was obtained (white solid, 14 mg, yield 35 %). 1H NMR (400 MHz, DMSO-d6) 5 11.10 (s, 1H), 8.80 (d, J = 4.0 Hz, 1H), 8.03 - 7.89 (m, 1H), 7.89 - 7.61 (m, 3H), 7.60 - 7.32 (m, 6H), 7.32 - 7.00 (m, 2H), 5.09 (dd, J = 12.9, 5.4 Hz, 1H), 3.81 (s, 3H), 3.30 - 3.06 (m, 6H), 2.87 (t, 1H), 2.70 - 2.53 (m, 2H), 2.08 - 1.97 (m, 1H). LCMS (ESI) calcd. for C29H29N6O4+ [M+H]+: 525.22, found, 525.3.

[0433] Example 81: Preparation of compound GT-06902

[0434] With reference to the method of Scheme 1, the target compound GT-06902 was obtained (white solid, 16 mg, yield 40 %). 1H NMR (400 MHz, DMSO-d6) 5 11.09 (s, 1H), 7.90 (d, J = 6.1, 3.2 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.56 - 7.49 (m, 3H), 7.43 - 7.35 (m, 5H), 7.32 - 7.24 (m, 2H), 5.08 (dd, J = 12.9, 5.3 Hz, 1H), 3.68 - 3.59 (m, 4H), 3.20 - 3.11 (m, 4H), 2.88 (td, J = 14.2, 7.5 Hz, 1H), 2.66 - 2.52 (m, 2H), 2.13 - 1.88 (m, 1H). LCMS (ESI) calcd. for C30H27ClN5O4+ [M+H]+: 556.17, found, 556.2.

[0435] Example 82: Preparation of compound GT-07209

[0436] With reference to the method of Scheme 1, the target compound GT-07209 was obtained (white solid, 5 mg, yield 6 %). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 7.93 - 7.87 (m, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.57 - 7.46 (m, 3H), 7.42 - 7.35 (m, 4H), 7.32 - 7.25 (m, 2H), 5.07 (dd, J = 13.0, 5.4 Hz, 1H), 3.63 (s, 4H), 3.27 - 3.20 (m, 2H), 3.16 (s, 4H), 2.94 - 2.76 (m, 2H), 2.59 (d, J = 16.6 Hz, 1H), 2.08 - 1.98 (m, 1H). LCMS (ESI) calcd. for C30H29ClN5O4+ [M+H]+: 558.19, found, 558.2

[0437] Example 83: Preparation of compound GT-06903

[0438] With reference to the method of Scheme 1, the target compound GT-06903 was obtained (white solid, 22 mg, yield 56 %). 1H NMR (400 MHz, DMSO-d6) 8 11.10 (s, 1H), 7.74 - 7.61 (m, 1H), 7.46 - 7.31 (m, 3H), 7.31 - 7.21 (m, 4H), 5.09 (dd, J = 12.8, 5.4 Hz, 1H), 3.70 - 3.52 (m, 5H), 3.21 (d, J = 25.8 Hz, 2H), 3.14 - 2.64 (m, 5H), 2.64 - 2.54 (m, 2H), 2.50 - 2.30 (m, 3H), 2.06 - 2.00 (m, 1H), 1.80 - 1.60 (m, 3H). LCMS (ESI) calcd. for C30H31FN5O4+ [M+H]+: 544.24, found, 554.3.

[0439] Example 84: Preparation of compound GT-07211

[0440] With reference to the method of Scheme 1, the target compound GT-07211 was obtained (white solid, 22 mg, yield 27%). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 10.70 (s, 1H), 7.69 (dd, J = 14.0, 8.4 Hz, 1H), 7.45 - 7.19 (m, 6H), 5.08 (dd, J = 12.9, 5.5 Hz, 1H), 3.55 (s, 6H), 3.11 - 2.80 (m, 5H), 2.66 - 2.52 (m, 2H), 2.42 - 2.32 (m, 1H), 2.26 (s, 3H), 2.09 - 1.96 (m, 1H), 1.69 (s, 4H). LCMS (ESI) calcd. for C30H33FN5O4+ [M+H]+:  546.25, found, 546.3.

[0441] Example 85: Preparation of compound GT-06904

[0442] With reference to the method of Scheme 1, the target compound GT-06904 was obtained (white solid, 20 mg, yield 49 %). 1H NMR (400 MHz, DMSO-d6) 8 11.09 (s, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.39 - 7.31 (m, 3H), 7.30 - 7.22 (m, 2H), 5.07 (dd, J = 12.9, 5.4 Hz, 1H), 4.37 (s, 2H), 3.82 (t, J = 5.5 Hz, 2H), 3.62 - 3.54 (m, 4H), 3.07 - 2.96 (m, 4H), 2.93 -2.83 (m, 1H), 2.66 - 2.53 (m, 2H), 2.48 (s, 2H), 2.06 - 1.98 (m, 1H). LCMS (ESI) calcd. for C29H29ClN5O5+ [M+H]+: 562.19, found, 562.2.

[0443] Example 86: Preparation of compound GT-07212

[0444] With reference to the method of Scheme 1, the target compound GT-07212 was obtained (white solid, 8 mg, yield 10 %). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (d, J = 3.8 Hz, 1H), 7.78 - 7.65 (m, 1H), 7.52 - 7.24 (m, 6H), 5.14 - 4.94 (m, 1H), 4.32 (d, J = 34.9 Hz, 2H), 3.81 (t, J = 5.4 Hz, 2H), 3.66 - 3.54 (m, 6H), 3.15 - 2.97 (m, 4H), 2.91 - 2.81 (m, 1H), 2.64 - 2.53 (m, 2H), 2.48 - 2.31 (m, 2H), 2.03 (t, J = 12.3 Hz, 1H). LCMS (ESI) calcd. for C29H31ClN5O5+ [M+H]+: 564.20, found, 564.2

[0445] Example 87: Preparation of compound GT-06905

[0446] With reference to the method of Scheme 1, the target compound GT-06905 was obtained (white solid, 13 mg, yield 31 %). 1H NMR (400 MHz, DMSO-d6) 5 11.10 (s, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.37 (d, J = 2.1 Hz, 1H), 7.30 - 7.25 (m, 2H), 7.25 - 7.20 (m, 2H), 5.09 (dd, J = 12.9, 5.4 Hz, 1H), 3.62 - 3.55 (m, 4H), 3.05 - 2.94 (m, 4H), 2.93 - 2.83 (m, 1H), 2.67 - 2.54 (m, 2H), 2.40 (s, 2H), 2.18 (s, 2H), 2.04 (dd, J = 9.0, 3.7 Hz, 1H), 1.47 (t, J = 6.5 Hz, 2H), 0.99 (s, 6H). LCMS (ESI) calcd. for C32H35ClN5O4+ [M+H]+: 588.24, found, 588.3.

[0447] Example 88: Preparation of compound GT-07214

[0448] With reference to the method of Scheme 1, the target compound GT-07214 was obtained (white solid, 18 mg, yield 25 %). 1H NMR (400 MHz, DMSO-d6) 5 11.08 (s, 1H), 10.83 (s, 1H), 7.69 (dd, J = 14.3, 8.5 Hz, 1H), 7.41 (ddd, J = 24.0, 15.3, 5.1 Hz, 3H), 7.32 - 7.18 (m, 3H), 5.08 (dd, J = 12.9, 5.6 Hz, 1H), 3.57 (d, J = 4.8 Hz, 4H), 3.09 - 2.79 (m, 5H), 2.63 - 2.53 (m, 3H), 2.37 (d, J = 5.1 Hz, 1H), 2.21 (d, J = 43.8 Hz, 2H), 2.02 (d, J = 11.7 Hz, 3H), 1.44 (s, 2H), 0.97 (d, J = 5.0 Hz, 6H). LCMS (ESI) calcd. for C32H37ClN5O4+ [M+H]+: 590.25, found, 590.3.

[0449] Example 89: Preparation of compound GT-06907

[0450] With reference to the method of Scheme 1, the target compound GT-06907 was obtained (pale yellow solid, 28 mg, yield 43 %). 1H NMR (500 MHz, ) 5 11.13 (s, 1H), 11.03 (s,1H), 8.07 (d, J = 7.6 Hz,1H), 7.83 (s,1H), 7.65 (d, J = 8.3 Hz,2H), 7.51 (d, J = 8.4 Hz,2H), 7.42 - 7.39 (m,1H), 7.39 - 7.37 (m,1H), 7.35 (s,1H), 7.34 (s,1H), 7.26 (d, J = 7.4 Hz,1H), 7.24 (s,1H), 5.02 (dd, J = 12.8, 5.4 Hz,1H), 2.82 (d, J = 2.0 Hz,1H), 2.51 (t, J = 15.2 Hz,2H), 1.96 (d, J = 5.0 Hz,1H). LCMS (ESI) calcd. for C26H20ClN4O4+ [M+H]+: 487.12, found, 487.2.

[0451] Example 90: Preparation of compound GT-06908

[0452] With reference to the method of Scheme 1, the target compound GT-06908 was obtained (pale yellow solid, 21 mg, yield 33 %). 1H NMR (500 MHz, ) 5 11.01 (s,1H), 10.79 (s,1H), 7.60 (d, J = 8.3 Hz,1H), 7.52 (s,1H), 7.25 - 7.20 (m,2H), 7.18 (d, J = 8.9 Hz,2H), 4.99 (dd, J = 12.8, 5.4 Hz,1H), 3.26 (s,1H), 2.81 (d, J = 2.0 Hz,1H), 2.58 - 2.45 (m,2H), 2.40 (d, J = 4.6 Hz,1H), 2.36 (s,2H), 1.95 (d, J = 5.4 Hz,1H), 1.66 (s,4H). LCMS (ESI) calcd. for C26H24FN4O4+ [M+H]+: 475.18, found, 475.3.

[0453] Example 91: Preparation of compound GT-06909

[0454] With reference to the method of Scheme 1, the target compound GT-06909 was obtained (pale yellow solid, 10 mg, yield 15 %). 1H NMR (500 MHz, ) 5 11.10 (s, 1H), 10.90 (s, 1H), 7.69 (d, J = 8.3 Hz,1H), 7.61 (s,1H), 7.50 (d, J = 8.4 Hz,2H), 7.26 (d, J = 8.4 Hz,2H), 7.20 (s, 1H), 5.09 (dd, J = 12.8, 5.4 Hz,1H), 2.92 - 2.89 (m,1H), 2.60 (d, J = 19.8 Hz,1H), 2.54 (s, 2H), 2.23 (s, 2H), 2.06 - 2.02 (m, 1H), 1.54 (t, J = 6.5 Hz, 2H), 1.25 (s, 2H), 1.02 (s, 6H). LCMS (ESI) calcd. for C28H28ClN4O4+ [M+H]+: 519.18, found, 519.2.

[0455] Example 92: Preparation of compound GT-06906

[0456] With reference to the method of Scheme 1, the target compound GT-06906 was obtained (pale yellow solid, 6 mg, yield 10 %). LCMS (ESI) calcd. for C25H22N5O4+ [M+H]+: 456.17, found, 456.2.

[0457] Example 93: Preparation of compound GT-06910

[0458] With reference to the method of Scheme 1, the target compound GT-06910 was obtained (pale yellow solid, 10 mg, yield 12 %). LCMS (ESI) calcd. for C28H28ClN4O4+ [M+H]+: 519.18, found, 519.2.

[0459] Example 94: Preparation of compound GT-06962

[0460] With reference to the method of Scheme 1, the target compound GT-06962 was obtained (17 mg, white solid, yield 27%). 1H NMR (400 MHz, MeOD) 5 7.49 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.2 Hz, 1H), 7.37 - 7.31 (m, 1H), 7.24 (d, J = 8.4 Hz, 2H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.45 (q, J = 16.7 Hz, 2H), 4.33 (s, 2H), 3.94 (t, J = 5.5 Hz, 2H), 3.79 (s, 2H), 3.52 (d, J = 8.9 Hz, 2H), 3.20 - 3.09 (m, 2H), 3.03 - 2.93 (m, 4H), 2.87 (dd, J = 13.4, 5.2 Hz, 1H), 2.80 - 2.71 (m, 1H), 2.55 - 2.42 (m, 3H), 2.17 - 2.11 (m, 1H). LCMS (ESI) calcd. for C29H32ClFN5O4+ [M+H]+: 558.21, found, 568.3.

[0461] Example 95: Preparation of compound GT-06963

[0462] With reference to the method of Scheme 1, the target compound GT-06963 was obtained (17 mg, white solid, yield 27%). 1H NMR (400 MHz, MeOD) 5 7.47 (d, J = 8.2 Hz, 2H), 7.23 (d, J = 8.2 Hz, 2H), 6.72 (s, 1H), 6.60 (d, J = 12.7 Hz, 1H), 5.03 (dd, J = 13.8, 5.5 Hz, 1H), 4.42 -4.25 (m, 4H), 4.01 - 3.87 (m, 2H), 3.85 - 3.71 (m, 2H), 3.54 - 3.45 (m, 2H), 3.19 - 3.07 (m, 2H), 3.05 - 2.84 (m, 5H), 2.80 - 2.71 (m, 1H), 2.54 - 2.45 (m, 2H), 2.44 - 2.37 (m, 1H), 2.18 - 2.03 (m, 1H). LCMS (ESI) calcd. for C29H32ClFN5O4+ [M+H]+: 558.21, found, 568.3.

[0463] Example 96: Preparation of compound GT-07990

[0464] With reference to the method of Scheme 1, the target compound GT-07990 was obtained (27 mg, white solid, yield 48%). LCMS (ESI) calcd. for C34H42ClN6O5+ [M+H]+: 649.29, found, 649.2.

[0465] Example 97: Preparation of compound GT-07996

[0466] With reference to the method of Scheme 1, the target compound GT-07996 was obtained (33 mg, white solid, yield 58%). LCMS (ESI) calcd. for C34H40ClN6O6+ [M+H]+: 663.27, found, 663.2.

[0467] Example 98: Preparation of compound GT-08034

[0468] With reference to the method of Scheme 1, the target compound GT-08034 was obtained (10 mg, white solid, yield 55%). 1H NMR (400 MHz, MeOD) 5 7.55 - 7.47 (m, 3H), 7.36 - 7.28 (m, 2H), 6.99 (s, 1H), 6.92 - 6.88 (m, 1H), 5.28 - 5.00 (m, 3H), 4.40 - 4.31 (m, 1H), 4.14 (s, 1H), 3.84 (s, 1H), 3.67 - 3.61 (m, 2H), 3.53 - 3.48 (m, 1H), 3.30 (s, 4H), 3.17 - 3.10 (m, 2H), 3.02 -2.83 (m, 2H), 2.82 - 2.68 (m, 2H), 2.55 - 2.36 (m, 1H), 2.20 - 2.09 (m, 1H), 2.09 - 1.98 (m, 2H). LCMS (ESI) calcd. for C29H34ClFN6O3+ [M+H]+: 549.24, found, 549.2.

[0469] Example 99: Preparation of compound GT-08040

[0470] With reference to the method of Scheme 1, the target compound GT-08040 was obtained (15 mg, white solid, yield 66%). 1H NMR (400 MHz, MeOD) 5 7.59 (d, J = 8.2 Hz, 1H), 7.52 (d, J = 8.3 Hz, 2H), 7.33 - 7.23 (m, 3H), 7.06 (d, J = 8.0 Hz, 1H), 5.04 (dd, J = 13.3, 6.2 Hz, 1H), 4.13 (s, 2H), 3.84 (s, 2H), 3.67 - 3.56 (m, 2H), 3.56 - 3.46 (m, 2H), 3.12 (s, 4H), 2.99 (s, 2H), 2.88 - 2.64 (m, 5H), 2.14 - 2.04 (m, 1H). LCMS (ESI) calcd. for C29H32ClN6O4+ [M+H]+: 563.22, found, 563.2.

[0471] Example 100: Preparation of compound GT-08865

[0472] With reference to the method of Scheme 5, the target compound GT-08865 was obtained (46 mg, white solid, yield 46%). 1H NMR (400 MHz, DMSO-d6) 5 11.10 (s, 1H), 7.62 (t, J = 7.5 Hz, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.28 (s, 1H), 7.11 (d, J = 6.7 Hz, 1H), 5.16 - 4.98 (m, 1H), 2.84 (d, J = 36.1 Hz, 6H), 2.59 (d, J = 18.7 Hz, 5H), 2.08 - 1.98 (m, 1H), 1.04 (s, 9H). LCMS (ESI) calcd. for C21H28N5O4+ [M+H]+: 414.21, found, 414.3.

[0473] Example 101: Preparation of compound GT-08531

[0474] With reference to the method of Scheme 5, the target compound GT-08531 was obtained (630 mg, white solid, yield 35%). 1H NMR (400 MHz, DMSO-d6) 5 11.06 (s, 1H), 8.05 (s, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.14 (s, 1H), 7.01 (d, J = 7.8 Hz, 1H), 5.04 (dd, J = 12.9, 5.4 Hz, 1H), 2.92 - 2.83 (m, 1H), 2.73 (dd, J = 45.1, 17.9 Hz, 4H), 2.57 (dd, J = 19.7, 5.9 Hz, 4H), 2.46 (d, J = 4.3 Hz, 2H), 2.20 (s, 3H), 2.03 - 1.96 (m, 1H). LCMS (ESI) calcd. for C18H22N5O4+ [M+H]+: 372.17, found, 372.2.

[0475] Example 102: Preparation of compound GT-08644

[0476] With reference to the method of Scheme 5, the target compound GT-08644 was obtained (110 mg, white solid, yield 38%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 7.43 (d, J = 8.3 Hz, 1H), 7.25 (s, 1H), 6.90 (s, 1H), 6.85 - 6.78 (m, 1H), 5.02 (dd, J = 13.3, 5.1 Hz, 1H), 4.30 (d, J = 16.8 Hz, 1H), 4.16 (d, J = 16.8 Hz, 1H), 2.95 - 2.85 (m, 1H), 2.72 (s, 4H), 2.59 (d, J = 17.5 Hz, 2H), 2.45 (s, 2H), 2.34 (ddd, J = 26.4, 13.3, 4.4 Hz, 2H), 2.20 (s, 3H), 1.99 - 1.91 (m, 1H). LCMS (ESI) calcd. for C18H24N5O3+ [M+H]+: 358.19, found, 358.2.

[0477] Example 103: Preparation of compound GT-08711

[0478] With reference to the method of Scheme 5, the target compound GT-08711 was obtained (43 mg, white solid, yield 21%).1H NMR (400 MHz, DMSO-d6) 5 11.06 (s, 1H), 8.01 (s, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.16 (s, 1H), 7.03 (s, 1H), 5.04 (dd, J = 12.9, 5.4 Hz, 1H), 2.93 - 2.82 (m, 2H), 2.70 (d, J = 23.7 Hz, 4H), 2.65 - 2.52 (m, 4H), 2.15 - 1.55 (m, 2H), 1.04 (s, 9H). LCMS (ESI) calcd. for C21H28N5O4+ [M+H]+: 414.21, found, 414.3.

[0479] Example 104: Preparation of compound GT-09057

[0480] With reference to the method of Scheme 5, the target compound GT-09057 was obtained (63 mg, white solid, yield 41%). 1H NMR (400 MHz, DMSO-d6) 5 11.01 (s, 1H), 9.71 (s, 1H), 7.31 (t, J = 7.7 Hz, 1H), 7.14 (s, 1H), 7.09 (s, 1H), 7.07 (d, J = 1.2 Hz, 1H), 5.10 (dd, J = 13.3, 5.0 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.22 (d, J = 17.4 Hz, 1H), 3.46 - 3.43 (m, 2H), 3.21 (d, J = 8.7 Hz, 2H), 3.15 (d, J = 12.9 Hz, 2H), 2.99 - 2.89 (m, 1H), 2.84 (s, 3H), 2.79 (s, 2H), 2.62 (d, J = 17.1 Hz, 1H), 2.39 (ddd, J = 26.5, 13.3, 4.4 Hz, 1H), 2.07 - 1.98 (m, 1H). LCMS (ESI) calcd. for C18H24N5O3+ [M+H]+: 358.19, found, 358.2.

[0481] Example 105: Preparation of compound GT-09058

[0482] With reference to the method of Scheme 5, the target compound GT-09058 was obtained (190 mg, white solid, yield 50%). 1H NMR (400 MHz, DMSO-d6) 8 11.11 (s, 1H), 9.75 (s, 1H), 7.95 (s, 1H), 7.65 (dd, J = 8.4, 7.2 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 7.15 (d, J = 6.7 Hz, 1H), 5.07 (dd, J = 12.7, 5.4 Hz, 1H), 3.47 (s, 2H), 3.27 (s, 2H), 3.09 (s, 4H), 2.93 (d, J = 5.9 Hz, 1H), 2.83 (s, 3H), 2.59 (d, J = 19.1 Hz, 1H), 2.54 (s, 1H), 2.10 - 1.99 (m, 1H). LCMS (ESI) calcd. for C18H22N5O4+ [M+H]+: 372.17, found, 372.2.

[0483] Example 106: Preparation of compound GT-09917

[0484] With reference to the method of Scheme 5, the target compound GT-09917 was obtained (51 mg, white solid, yield 31%). 1H NMR (400 MHz, DMSO-d6) 8 11.09 (s, 1H), 8.15 (s, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.51 - 7.39 (m, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 3.35 - 3.30 (m, 4H), 2.88 - 2.82 (m, 1H), 2.73 (s, 4H), 2.63 - 2.51 (m, 2H), 2.02 (d, J = 5.7 Hz, 1H), 1.41 (d, J = 8.2 Hz, 9H). LCMS (ESI) calcd. for C22H27FN5O6+ [M+H]+: 476.19, found, 476.2.

[0485] Example 107: Preparation of compound GT-09918

[0486] With reference to the method of Scheme 5, the target compound GT-09918 was obtained (53 mg, white solid, yield 34%). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 8.51 (s, 1H), 7.00 (s, 1H), 6.79 (s, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 3.36 (s, 4H), 2.88 (ddd, J = 16.8, 14.0, 5.5 Hz, 4H), 2.58 (dd, J = 17.2, 2.4 Hz, 2H), 2.46 (dd, J = 13.3, 4.3 Hz, 1H), 2.05 - 1.97 (m, 1H), 1.42 (s, 9H). LCMS (ESI) calcd. for C22H27FN5O6+ [M+H]+: 476.19, found, 476.2.

[0487] Example 108: Preparation of compound GT-09919

[0488] With reference to the method of Scheme 5, the target compound GT-09919 was obtained (32 mg, white solid, yield 19%). 1H NMR (400 MHz, DMSO-d6) 8 11.03 (s, 1H), 8.03 (s, 1H), 6.79 (s, 1H), 6.47 (s, 1H), 5.00 (dd, J = 12.8, 5.4 Hz, 1H), 3.47 (d, J = 11.2 Hz, 4H), 3.35 (s, 4H), 3.30 (s, 4H), 3.16 (s, 4H), 2.90 - 2.83 (m, 1H), 2.61 - 2.52 (m, 2H), 1.97 (dd, J = 10.8, 5.7 Hz, 1H), 1.42 (d, J = 3.1 Hz, 18H). LCMS (ESI) calcd. for C31H44N7O8+ [M+H]+: 642.32, found, 642.4.

[0489] Example 109: Preparation of compound GT-08710

[0490] With reference to the method of Scheme 5, the target compound GT-08710 was obtained (68 mg, white solid, yield 35%).1H NMR (400 MHz, DMSO-d6) 5 11.06 (s, 1H), 8.06 (s, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.15 (s, 1H), 7.02 (d, J = 7.1 Hz, 1H), 5.04 (dd, J = 12.9, 5.3 Hz, 1H), 2.95 - 2.51 (m, 12H), 1.99 (dd, J = 9.5, 6.3 Hz, 1H), 1.00 (d, J = 5.3 Hz, 6H). LCMS (ESI) calcd. for C20H26N5O4+ [M+H]+: 400.20, found, 400.3.

[0491] Example 110: Preparation of compound GT-08881

[0492] With reference to the method of Scheme 5, the target compound GT-08881 was obtained (53 mg, white solid, yield 36%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 7.43 (d, J = 8.3 Hz, 1H), 7.27 (s, 1H), 6.90 (s, 1H), 6.83 (d, J = 8.2 Hz, 1H), 5.02 (dd, J = 13.3, 5.1 Hz, 1H), 4.29 (d, J = 16.8 Hz, 1H), 4.16 (d, J = 16.9 Hz, 1H), 2.96 - 2.82 (m, 2H), 2.74 (s, 5H), 2.58 (d, J = 16.4 Hz, 4H), 2.33 (dd, J = 13.1, 4.4 Hz, 1H), 1.93 (dd, J = 12.0, 6.9 Hz, 1H), 1.02 (s, 6H). LCMS (ESI) calcd. for C20H27N5O3+ [M+H]+: 385.21, found, 385.3.

[0493] Example 111: Preparation of compound GT-08880

[0494] With reference to the method of Scheme 5, the target compound GT-08880 was obtained (16 mg, white solid, yield 20%). 1H NMR (400 MHz, DMSO-d6) 5 11.01 (s, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.04 (dd, J = 15.3, 7.4 Hz, 2H), 6.76 (s, 1H), 5.09 (dd, J = 13.1, 4.8 Hz, 1H), 4.28 (dd, J = 39.5, 17.3 Hz, 2H), 3.00 - 2.85 (m, 2H), 2.82 - 2.53 (m, 8H), 2.44 - 2.25 (m, 2H), 2.08 - 2.00 (m, 1H), 0.99 (s, 6H). LCMS (ESI) calcd. for C20H28N5O3+ [M+H]+: 386.22, found, 386.3.

[0495] Example 112: Preparation of compound GT-08866

[0496] With reference to the method of Scheme 5, the target compound GT-08866 was obtained (142 mg, white solid, yield 38%). 1H NMR (400 MHz, DMSO-d6) 5 11.10 (s, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.33 (s, 1H), 7.10 (d, J = 6.8 Hz, 1H), 5.05 (dd, J = 12.3, 4.9 Hz, 1H), 2.81 (dd, J = 41.7, 21.4 Hz, 5H), 2.69 - 2.51 (m, 7H), 2.07 - 1.97 (m, 1H), 0.98 (d, J = 6.2 Hz, 6H). LCMS (ESI) calcd. for C20H26N5O4+ [M+H]+: 400.20, found, 400.3.

[0497] Example 113: Preparation of compound GT-09018

[0498] With reference to the method of Scheme 5, the target compound GT-09018 was obtained (8 mg, white solid, yield 18%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 8.20 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.19 (s, 1H), 6.90 (s, 1H), 6.82 (d, J = 8.3 Hz, 1H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.29 (d, J = 16.8 Hz, 1H), 4.15 (d, J = 16.8 Hz, 1H), 2.89 (s, 2H), 2.76 - 2.56 (m, 8H), 2.33 (qd, J = 13.7, 9.0 Hz, 1H), 2.01 - 1.90 (m, 1H), 1.03 (s, 9H). LCMS (ESI) calcd. for C21HsoN5O3+ [M+H]+: 400.23, found, 400.3.

[0499] Example 114: Preparation of compound GT-09138

[0500] With reference to the method of Scheme 5, the target compound GT-09138 was obtained (13 mg, white solid, yield 20%). 1H NMR (400 MHz, MeOD) 5 7.35 (t, J = 7.7 Hz, 1H), 7.25 (d, J = 3.4 Hz, 1H), 7.23 (dd, J = 4.7, 0.9 Hz, 1H), 5.14 (dd, J = 13.2, 5.2 Hz, 1H), 4.44 (s, 2H), 3.64 (d, J = 12.2 Hz, 2H), 3.42 - 3.32 (m, 4H), 3.02 - 2.86 (m, 3H), 2.84 - 2.75 (m, 1H), 2.57 - 2.45 (m, 1H), 2.26 - 2.12 (m, 1H), 1.47 (s, 9H). LCMS (ESI) calcd. for C21H30N5O3+ [M+H]+: 400.23, found, 400.3.

[0501] Example 115: Preparation of compound GT-09129

[0502] With reference to the method of Scheme 2, the target compound GT-09129 was obtained (24 mg, white solid, yield 39%). 1H NMR (400 MHz, MeOD) 5 7.73 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 8.2 Hz, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.04 (s, 1H), 6.96 (dd, J = 8.4, 1.7 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.46 (s, 2H), 4.43 - 4.28 (m, 4H), 3.54 (d, J = 12.4 Hz, 2H), 3.48 - 3.41 (m, 4H), 3.29 - 3.16 (m, 3H), 3.06 - 2.93 (m, 4H), 2.82 - 2.72 (m, 1H), 2.51 - 2.40 (m, 1H), 2.20 -2.08 (m, 1H), 1.94 (d, J = 14.7 Hz, 2H), 1.88 - 1.75 (m, 3H), 1.57 - 1.52 (m, 1H). LCMS (ESI) calcd. for C30H39N6O3+ [M+H]+: 531.31, found, 531.3.

[0503] Example 116: Preparation of compound GT-09130

[0504] With reference to the method of Scheme 2, the target compound GT-09130 was obtained (13 mg, white solid, yield 26%). 1H NMR (400 MHz, MeOD) 5 7.73 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 7.48 (t, J = 7.3 Hz, 1H), 7.44 - 7.38 (m, 1H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.53 - 4.45 (m, 4H), 4.36 (s, 2H), 3.55 (d, J = 11.3 Hz, 2H), 3.45 - 4.39 (m, 4H), 3.28 - 3.22 (m, 2H), 3.13 - 3.03 (m, 4H), 2.77 (d, J = 15.6 Hz, 1H), 2.56 - 2.41 (m, 1H), 2.37 - 2.32 (m, 1H), 2.24 -2.10 (m, 1H), 1.94 (d, J = 14.2 Hz, 2H), 1.89 - 1.73 (m, 3H), 1.55 - 1.51 (m, 1H). LCMS (ESI) calcd. for C30H38FN6O3+ [M+H]+: 549.30, found, 549.3.

[0505] Example 117: Preparation of compound GT-09131

[0506] With reference to the method of Scheme 2, the target compound GT-09131 was obtained (33 mg, white solid, yield 67%).1H NMR (400 MHz, MeOD) 5 7.74 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 7.0 Hz, 1H), 7.35 (d, J = 10.5 Hz, 1H), 5.09 (dd, J = 13.3, 5.2 Hz, 1H), 4.47 (s, 2H), 4.43 - 4.29 (m, 4H), 3.55 (d, J = 12.2 Hz, 2H), 3.47 - 3.40 (m, 4H), 3.25 (d, J = 12.1 Hz, 2H), 3.16 - 3.06 (m, 2H), 3.04 - 2.95 (m, 2H), 2.82 - 2.72 (m, 1H), 2.53 - 2.42 (m, 1H), 2.40 - 2.33 (m, 1H), 2.24 - 2.10 (m, 1H), 1.94 (d, J = 14.5 Hz, 2H), 1.86 - 1.75 (m, 3H), 1.56 - 1.51 (m, 1H). LCMS (ESI) calcd. for C30H38FN6O3+ [M+H]+: 549.30, found, 549.3.

[0507] Example 118: Preparation of compound GT-09132

[0508] With reference to the method of Scheme 2, the target compound GT-09132 was obtained (29 mg, white solid, yield 59%). 1H NMR (400 MHz, MeOD) 5 7.73 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 8.2 Hz, 2H), 6.78 (s, 1H), 6.67 (d, J = 11.9 Hz, 1H), 5.04 (dd, J = 13.3, 5.1 Hz, 1H), 4.46 (s, 2H), 4.42 - 4.27 (m, 4H), 3.53 (d, J = 12.3 Hz, 2H), 3.48 - 3.39 (m, 4H), 3.25 - 3.20 (m, 2H), 3.00 (t, J = 12.1 Hz, 4H), 2.80 - 2.71 (m, 1H), 2.53 - 2.28 (m, 2H), 2.20 - 2.07 (m, 1H), 1.94 (d, J = 14.5 Hz, 2H), 1.86 - 1.75 (m, 3H), 1.59 - 1.44 (m, 1H). LCMS (ESI) calcd. for C30H38FN6O3+ [M+H]+: 549.30, found, 549.3.

[0509] Example 119: Preparation of compound GT-09133

[0510] With reference to the method of Scheme 2, the target compound GT-09133 was obtained (32 mg, white solid, yield 65%).1H NMR (400 MHz, MeOD) 5 7.74 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 7.7 Hz, 1H), 7.23 (d, J = 6.5 Hz, 1H), 7.21 - 7.15 (m, 1H), 5.15 (dd, J = 13.2, 5.2 Hz, 1H), 4.56 - 4.45 (m, 4H), 4.35 (s, 2H), 3.57 - 3.49 (m, 2H), 3.47 - 3.41 (m, 4H), 3.02 - 2.96 (m, 4H), 2.82 - 2.77 (m, 1H), 2.58 - 2.50 (m, 1H), 2.48 - 2.34 (m, 2H), 2.31 - 2.27 (m, 1H), 2.24 - 2.10 (m, 1H), 1.92 (d, J = 15.2 Hz, 2H), 1.85 - 1.77 (m, 3H), 1.59 - 1.45 (m, 1H). LCMS (ESI) calcd. for C30H39N6O3+ [M+H]+: 531.31, found, 531.3.

[0511] Example 120: Preparation of compound GT-09134

[0512] With reference to the method of Scheme 2, the target compound GT-09134 was obtained (24 mg, white solid, yield 49%). LCMS (ESI) calcd. for C32H41N6O3+ [M+H]+: 557.32, found, 557.3.

[0513] Example 121: Preparation of compound GT-09135

[0514] With reference to the method of Scheme 2, the target compound GT-09135 was obtained (30 mg, white solid, yield 61%). 1H NMR (400 MHz, MeOD) 5 7.79 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 8.2 Hz, 2H), 7.57 (d, J = 8.3 Hz, 1H), 7.02 (s, 1H), 6.95 (d, J = 8.3 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.46 - 4.29 (m, 6H), 4.01 (s, 2H), 3.46 (d, J = 12.6 Hz, 2H), 3.19 - 3.11 (m, 4H), 3.06 - 2.94 (m, 2H), 2.93 - 2.83 (m, 1H), 2.80 - 2.74 (m, 1H), 2.51 - 2.44 (m, 4H), 2.41 - 2.33 (m, 1H), 2.19 - 2.11 (m, 2H), 1.93 (d, J = 15.0 Hz, 2H), 1.88 - 1.73 (m, 3H), 1.60 - 1.47 (m, 1H). LCMS (ESI) calcd. for C32H41N6O3+ [M+H]+: 557.32, found, 557.3.

[0515] Example 122: Preparation of compound GT-09197

[0516] With reference to the method of Scheme 2, the target compound GT-09197 was obtained (16 mg, white solid, yield 33%). 1H NMR (400 MHz, MeOD) 5 7.66 (s, 4H), 7.57 (d, J = 8.2 Hz, 1H), 7.08 (s, 1H), 6.98 (d, J = 8.2 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.63 (s, 2H), 4.42 -4.30 (m, 2H), 4.45 - 4.27 (m, 4H), 4.05 (t, J = 10.8 Hz, 2H), 3.88 (s, 1H), 3.40 (d, J = 11.4 Hz, 2H), 3.03 - 2.81 (m, 5H), 2.73 (d, J = 15.6 Hz, 1H), 2.49 - 2.30 (m, 2H), 2.18 - 2.04 (m, 5H), 1.91 (d, J = 14.7 Hz, 2H), 1.79 (t, J = 12.8 Hz, 3H), 1.57 - 1.42 (m, 1H). LCMS (ESI) calcd. for C33H43N6O3+ [M+H]+: 571.34, found, 571.3.

[0517] Example 123: Preparation of compound GT-09198

[0518] With reference to the method of Scheme 2, the target compound GT-09198 was obtained (26 mg, white solid, yield 53%).1H NMR (400 MHz, MeOD) 5 7.75 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.5 Hz, 1H), 7.06 (s, 1H), 6.95 (d, J = 8.0 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.49 (s, 2H), 4.46 - 4.29 (m, 4H), 3.67 - 3.54 (m, 2H), 3.54 - 3.44 (m, 4H), 3.28 -3.24 (m, 1H), 3.15 - 3.08 (m, 2H), 3.03 - 2.98 (m, 2H), 2.92 - 2.84 (m, 1H), 2.80 - 2.74 (m, 1H), 2.46 (dd, J = 13.2, 4.4 Hz, 1H), 2.42 - 2.33 (m, 1H), 2.24 - 2.09 (m, 3H), 1.92 (t, J = 13.8 Hz, 2H), 1.89 - 1.73 (m, 3H), 1.56 - 1.49 (m, 1H). LCMS (ESI) calcd. for C31H41N6O3+ [M+H]+: 545.32, found, 545.3.

[0519] Example 124: Preparation of compound GT-09199

[0520] With reference to the method of Scheme 2, the target compound GT-09199 was obtained (33 mg, white solid, yield 67%).1H NMR (400 MHz, MeOD) 5 7.68 - 7.52 (m, 5H), 7.12 - 7.03 (m, 1H), 6.99 - 6.92 (m, 1H), 5.08 (dd, J = 13.3, 5.0 Hz, 1H), 4.42 - 4.23 (m, 7H), 3.79 - 3.57 (m, 3H), 3.22 - 3.00 (m, 4H), 2.92 - 2.84 (m, 2H), 2.81 - 2.66 (m, 2H), 2.54 - 2.37 (m, 2H), 2.20 -2.12 (m, 2H), 1.84 (brs, 4H), 1.67 (brs, 2H). LCMS (ESI) calcd. for C31H39N6O3+ [M+H]+: 543.31, found, 543.3.

[0521] Example 125: Preparation of compound GT-09200

[0522] With reference to the method of Scheme 2, the target compound GT-09200 was obtained (33 mg, white solid, yield 67%). 1H NMR (400 MHz, MeOD) 5 7.79 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 7.58 - 7.51 (m, 1H), 7.07 (s, 1H), 6.99 - 6.91 (m, 1H), 5.07 (dd, J = 13.3, 5.0 Hz, 1H), 4.56 (d, J = 13.2 Hz, 1H), 4.45 - 4.31 (m, 6H), 3.83 - 3.74 (m, 1H), 3.69 - 3.53 (m, 1H), 3.45 (d, J = 12.2 Hz, 3H), 3.03 - 2.97 (m, 3H), 2.86 (dd, J = 12.5, 3.9 Hz, 1H), 2.76 (d, J = 17.8 Hz, 1H), 2.50 - 2.34 (m, 4H), 2.26 - 2.07 (m, 2H), 1.94 (d, J = 14.2 Hz, 2H), 1.85 - 1.78 (m, 3H), 1.58 - 1.44 (m, 1H). LCMS (ESI) calcd. for C31H39N6O3+ [M+H]+: 543.31, found, 543.3.

[0523] Example 126: Preparation of compound GT-09201

[0524] With reference to the method of Scheme 2, the target compound GT-09201 was obtained (34 mg, white solid, yield 69%).1H NMR (400 MHz, MeOD) 5 7.82 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 8.4 Hz, 1H), 7.20 (s, 1H), 7.08 (d, J = 8.4 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.49 (s, 2H), 4.43 - 4.30 (m, 4H), 3.60 (d, J = 11.5 Hz, 2H), 3.52 (s, 2H), 3.45 (d, J = 12.1 Hz, 2H), 3.37 - 3.34 (m, 2H), 3.00 (dt, J = 12.5, 6.3 Hz, 2H), 2.91 - 2.82 (m, 1H), 2.81 -2.70 (m, 1H), 2.51 - 2.42 (m, 1H), 2.39 - 2.24 (m, 3H), 2.19 - 2.06 (m, 3H), 1.93 (d, J = 14.5 Hz, 2H), 1.87 - 1.77 (m, 3H), 1.57 - 1.47(m, 1H). LCMS (ESI) calcd. for C32H41N6O3+ [M+H]+: 557.32, found, 557.3.

[0525] Example 127: Preparation of compound GT-09202

[0526] With reference to the method of Scheme 2, the target compound GT-09202 was obtained (37 mg, white solid, yield 75%). 1H NMR (400 MHz, MeOD) 5 7.74 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 8.2 Hz, 2H), 7.61 (d, J = 8.3 Hz, 1H), 7.32 (s, 1H), 7.12 (d, J = 7.3 Hz, 1H), 5.06 (dd, J = 12.5, 5.5 Hz, 1H), 4.47 (s, 2H), 4.36 (s, 2H), 3.55 (d, J = 12.2 Hz, 2H), 3.48 - 3.41 (m, 4H), 3.25 (d, J = 12.6 Hz, 2H), 3.13 - 2.98 (m, 4H), 2.90 - 2.80 (m, 1H), 2.77 - 2.74 (m, 1H), 2.68 - 2.65 (m, 1H), 2.13 - 2.09 (m, 1H), 1.94 (d, J = 14.6 Hz, 2H), 1.85 - 1.75 (m, 3H), 1.55 - 1.49 (m, 1H). LCMS (ESI) calcd. for C30H37N6O4+ [M+H]+: 545.29, found, 545.3.

[0527] Example 128: Preparation of compound GT-09203

[0528] With reference to the method of Scheme 2, the target compound GT-09203 was obtained (14 mg, white solid, yield 28%). 1H NMR (400 MHz, MeOD) 5 7.80 - 7.72 (m, 5H), 7.47 (d, J = 2.2 Hz, 1H), 7.36 (dd, J = 8.5, 2.3 Hz, 1H), 5.09 (dd, J = 12.4, 5.4 Hz, 1H), 4.39 (s, 2H), 4.06 (d, J = 14.0 Hz, 2H), 3.92 - 3.85 (m, 2H), 3.74 - 3.65 (m, 4H), 3.50 (d, J = 12.1 Hz, 2H), 3.29 - 3.25 (m, 1H), 3.02 (td, J = 12.3, 2.8 Hz, 2H), 2.90 - 2.81 (m, 1H), 2.80 - 2.74 (m, 1H), 2.73 (s, 1H), 2.70 (s, 1H), 2.19 - 2.06 (m, 1H), 1.94 (d, J = 14.0 Hz, 2H), 1.89 - 1.76 (m, 3H), 1.62 - 1.47 (m, 1H). LCMS (ESI) calcd. for C30H37N6O4+ [M+H]+: 545.29, found, 545.3.

[0529] Example 129: Preparation of compound GT-09213

[0530] With reference to the method of Scheme 2, the target compound GT-09213 was obtained (24 mg, white solid, yield 49%). 1H NMR (400 MHz, MeOD) 5 7.76 (q, J = 8.3 Hz, 4H), 7.69 (d, J = 8.5 Hz, 1H), 7.20 (s, 1H), 7.18 (dd, J = 8.5, 2.2 Hz, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.51 - 4.32 (m, 5H), 3.96 - 3.85 (m, 5H), 3.66 - 3.58 (m, 4H), 3.50 (d, J = 12.3 Hz, 2H), 3.05 - 2.98 (m, 2H), 2.92 - 2.84 (m, 1H), 2.82 - 2.72 (m, 1H), 2.47 (dd, J = 13.2, 4.7 Hz, 1H), 2.43 - 2.33 (m, 1H), 2.23 - 2.10 (m, 1H), 1.94 (d, J = 14.0 Hz, 2H), 1.89 - 1.80 (m, 3H), 1.61 - 1.49 (m, 1H). LCMS (ESI) calcd. for C30H39N6O3+ [M+H]+: 531.31, found, 531.3.

[0531] Example 130: Preparation of compound GT-09708

[0532] With reference to the method of Scheme 3, the target compound GT-09708 was obtained (36 mg, white solid, yield 48%). 1H NMR (400 MHz, DMSO-d6) 5 10.96 (s, 1H), 7.43 (t, J = 8.8 Hz, 4H), 7.32 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.9 Hz, 2H), 5.04 (dd, J = 13.2, 5.1 Hz, 1H), 4.45 (d, J = 16.7 Hz, 1H), 4.27 (d, J = 16.7 Hz, 1H), 3.77 (d, J = 13.8 Hz, 2H), 3.70 - 3.52 (m, 4H), 3.37 - 3.28 (m, 4H), 3.20 (t, J = 12.0 Hz, 2H), 2.90 - 2.73 (m, 6H), 2.59 (d, J = 16.3 Hz, 1H), 2.39 (d, J = 12.7 Hz, 1H), 2.34 - 2.22 (m, 3H), 2.11 (s, 2H), 1.99 - 1.94 (m, 1H), 1.48 (t, J = 6.4 Hz, 2H), 1.02 (s, 6H). LCMS (ESI) calcd. for C43H50ClFN7O4+ [M+H]+: 782.36, found, 782.4.

[0533] Example 131: Preparation of compound GT-09709

[0534] With reference to the method of Scheme 1, the target compound GT-09709 was obtained (20 mg, white solid, yield 28%). 1H NMR (400 MHz, DMSO-d6) 5 10.96 (s, 1H), 9.38 (s, 1H), 7.76 (s, 1H), 7.41 (d, J = 8.2 Hz, 1H), 7.29 (t, J = 7.7 Hz, 2H), 6.94 (d, J = 8.0 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 5.04 (dd, J = 13.3, 5.0 Hz, 1H), 4.45 (d, J = 16.8 Hz, 1H), 4.27 (d, J = 16.8 Hz, 1H), 4.21 (s, 2H), 3.81 (s, 3H), 3.30 - 3.27 (m, 2H), 3.24 - 3.15 (m, 2H), 3.07 (s, 4H), 2.96 - 2.84 (m, 1H), 2.59 (d, J = 17.3 Hz, 1H), 2.44 - 2.35 (m, 1H), 1.98 - 1.94 (m, 1H). LCMS (ESI) calcd. for C25H29FN5O5+ [M+H]+: 498.21, found, 498.2.

[0535] Example 132: Preparation of compound GT-09741

[0536] With reference to the method of Scheme 3, the target compound GT-09741 was obtained (19 mg, white solid, yield 33%). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 7.36 (d, J = 7.7 Hz, 1H), 7.27 (t, J = 7.7 Hz, 1H), 7.17 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 5.03 (dd, J = 13.3, 5.1 Hz, 1H), 4.43 (d, J = 16.8 Hz, 1H), 4.25 (d, J = 16.8 Hz, 1H), 4.10 (q, J = 6.4 Hz, 1H), 3.67 - 3.58 (m, 1H), 2.95 - 2.83 (m, 1H), 2.75 - 2.54 (m, 5H), 2.42 - 2.40 (m, 4H), 2.37 - 2.29 (m, 1H), 2.02 - 1.90 (m, 1H), 1.85 - 1.78 (m, 1H), 1.34 (d, J = 7.1 Hz, 1H), 1.28 (d, J = 6.8 Hz, 3H), 0.86 (dd, J = 6.6, 1.3 Hz, 6H). LCMS (ESI) calcd. for C30H37FN5O4+ [M+H]+: 550.28, found, 550.3.

[0537] Example 133: Preparation of compound GT-09971

[0538] With reference to the method of Scheme 2, the target compound GT-09971 was obtained (9 mg, white solid, yield 23%).1H NMR (400 MHz, MeOD) 5 7.69 - 7.66 (m, 4H), 7.57 - 7.51 (m, 5H), 7.07 - 7.03 (m, 2H), 5.82 (s, 1H), 5.17 - 5.06 (m, 1H), 4.46 - 4.35 (m, 2H), 3.80 - 3.60 (m, 2H), 3.27 - 3.18 (m, 3H), 3.12 - 3.02 (m, 3H), 2.99 - 2.96 (m, 1H), 2.92 - 2.89 (m, 1H), 2.82 -2.76 (m, 1H), 2.70 - 2.60 (m, 1H), 2.52 - 2.39 (m, 1H), 2.23 - 2.11 (m, 1H). LCMS (ESI) calcd. for C32H32Cl2N5O3+ [M+H]+: 604.19, found, 604.2.

[0539] Example 134: Preparation of compound GT-09972

[0540] With reference to the method of Scheme 3, the target compound GT-09972 was obtained (25 mg, white solid, yield 49%). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 7.56 - 7.52 (m, 3H), 7.50 - 7.40 (m, 6H), 6.82 (s, 1H), 6.74 (d, J = 8.1 Hz, 1H), 5.03 (dd, J = 13.3, 5.1 Hz, 1H), 4.31 (dd, J = 16.7, 6.2 Hz, 1H), 4.18 (d, J = 17.0 Hz, 1H), 2.96 - 2.86 (m, 2H), 2.78 - 2.65 (m, 5H), 2.62 - 2.55 (m, 4H), 2.43 - 2.32 (m, 2H), 2.02 - 1.92 (m, 1H). LCMS (ESI) calcd. for C32H31ClN5O4+ [M+H]+: 584.21, found, 584.2.

[0541] Example 135: Preparation of compound GT-09973

[0542] With reference to the method of Scheme 3, the target compound GT-09973 was obtained (35 mg, white solid, yield 68%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.57 - 7.51 (m, 3H), 7.50 - 7.40 (m, 6H), 6.84 (s, 1H), 6.77 (d, J = 8.0 Hz, 1H), 5.00 (dd, J = 13.2, 5.0 Hz, 1H), 4.53 (s, 1H), 4.27 (dd, J = 16.9, 3.2 Hz, 1H), 4.14 (dd, J = 17.0, 3.3 Hz, 1H), 3.54 - 3.42 (m, 2H), 2.97 - 2.81 (m, 2H), 2.71 - 2.65 (m, 2H), 2.63 - 2.54 (m, 3H), 2.35 - 2.24 (m, 1H), 1.99 - 1.79 (m, 2H), 1.69 (brs, 1H). LCMS (ESI) calcd. for C32H31ClN5O4+ [M+H]+: 584.21, found, 584.2.

[0543] Example 136: Preparation of compound GT-09974

[0544] With reference to the method of Scheme 3, the target compound GT-09974 was obtained (29 mg, white solid, yield 57%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.56 - 7.52 (m, 3H), 7.49 - 7.39 (m, 7H), 6.87 (s, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.28 (d, J = 16.9 Hz, 1H), 4.14 (d, J = 16.9 Hz, 1H), 3.54 - 3.43 (m, 4H), 3.21 (s, 2H), 2.96 - 2.83 (m, 1H), 2.59 - 2.54 (m, 2H), 2.38 - 2.25 (m, 2H), 1.97 - 1.91 (m, 1H), 1.55 (brs, 2H), 1.44 (brs, 2H). LCMS (ESI) calcd. for C33H33ClN5O4+ [M+H]+: 598.22, found, 598.3.

[0545] Example 137: Preparation of compound GT-09975

[0546] With reference to the method of Scheme 3, the target compound GT-09975 was obtained (26 mg, white solid, yield 50%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 7.56 - 7.51 (m, 3H), 7.51 - 7.38 (m, 6H), 6.90 (s, 1H), 6.83 (s, 1H), 5.02 (dd, J = 13.3, 5.1 Hz, 1H), 4.30 (d, J = 16.8 Hz, 1H), 4.19 (d, J = 16.8 Hz, 1H), 3.61 - 3.57 (m, 4H), 3.26 - 3.11 (m, 1H), 3.05 - 2.75 (m, 4H), 2.58 (d, J = 16.9 Hz, 2H), 2.40 - 2.26 (m, 1H), 1.97 - 1.93 (m, 1H), 1.69 (brs, 1H). LCMS (ESI) calcd. for C31H31ClN5O4+ [M+H]+: 572.21, found, 572.2.

[0547] Example 138: Preparation of compound GT-09976

[0548] With reference to the method of Scheme 3, the target compound GT-09976 was obtained (32 mg, white solid, yield 62%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.57 - 7.53 (m, 5H), 7.49 - 7.42 (m, 4H), 6.86 (s, 1H), 6.79 (d, J = 8.3 Hz, 1H), 5.01 (dd, J = 13.3, 5.0 Hz, 1H), 4.28 (d, J = 16.9 Hz, 1H), 4.15 (d, J = 17.0 Hz, 1H), 3.60 (s, 1H), 3.23 (s, 2H), 3.12 - 2.99 (m, 1H), 2.94 - 2.83 (m, 1H), 2.70 - 2.63 (m, 1H), 2.60 - 2.55 (m, 2H), 2.37 - 2.28 (m, 1H), 2.04 -1.87 (m, 2H), 1.64 (s, 1H). LCMS (ESI) calcd. for C31H29ClN5O4+ [M+H]+: 570.19, found, 570.2.

[0549] Example 139: Preparation of compound GT-09977

[0550] With reference to the method of Scheme 3, the target compound GT-09977 was obtained (29 mg, white solid, yield 56%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.58 - 7.51 (m, 4H), 7.50 - 7.36 (m, 5H), 6.91 (s, 1H), 6.81 (d, J = 8.4 Hz, 1H), 5.08 - 4.96 (m, 1H), 4.33 - 4.24 (m, 1H), 4.15 (d, J = 16.3 Hz, 1H), 3.68 - 3.63 (m, 4H), 3.21 - 3.08 (m, 1H), 2.97 - 2.81 (m, 2H), 2.58 (d, J = 18.1 Hz, 2H), 2.37 - 2.29 (m, 1H), 2.02 - 1.87 (m, 1H), 1.82 - 1.64 (m, 1H). LCMS (ESI) calcd. for C31H29ClN5O4+ [M+H]+: 570.19, found, 570.2.

[0551] Example 140: Preparation of compound GT-09978

[0552] With reference to the method of Scheme 3, the target compound GT-09978 was obtained (27 mg, white solid, yield 52%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.60 - 7.44 (m, 7H), 7.39 (d, J = 8.4 Hz, 2H), 6.95 (s, 1H), 6.88 (t, J = 8.7 Hz, 1H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.28 (d, J = 16.8 Hz, 1H), 4.13 (dd, J = 17.0, 3.4 Hz, 1H), 3.56 - 3.51 (m, 4H), 3.30 - 3.18 (m, 2H), 2.98 - 2.84 (m, 2H), 2.58 (d, J = 16.8 Hz, 2H), 2.36 - 2.30 (m, 1H), 2.07 - 1.88 (m, 2H), 1.66 - 1.53 (m, 1H). LCMS (ESI) calcd. for C32H31ClN5O4+ [M+H]+: 584.21, found, 584.3.

[0553] Example 141: Preparation of compound GT-09980

[0554] With reference to the method of Scheme 3, the target compound GT-09980 was obtained (14 mg, white solid, yield 26%). 1H NMR (400 MHz, DMSO-d6) 8 10.94 (s, 1H), 7.43 (s, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 6.78 (s, 1H), 6.74 - 6.67 (m, 1H), 5.03 (dd, J = 13.4, 4.3 Hz, 1H), 4.30 (d, J = 16.7 Hz, 1H), 4.17 (d, J = 16.8 Hz, 1H), 3.32 - 3.20 (m, 5H), 2.95 - 2.84 (m, 2H), 2.72 - 2.63 (m, 2H), 2.63 - 2.55 (m, 4H), 2.39 - 2.27 (m, 4H), 1.98 - 1.91 (m, 1H), 1.45 (t, J = 6.3 Hz, 2H), 0.99 (s, 6H). LCMS (ESI) calcd. for C34H39ClN5O4+ [M+H]+: 616.27, found, 616.3.

[0555] Example 142: Preparation of compound GT-09981

[0556] With reference to the method of Scheme 3, the target compound GT-09981 was obtained (24 mg, white solid, yield 44%). 1H NMR (400 MHz, DMSO-d6) 8 10.92 (s, 1H), 7.42 - 7.38 (m, 3H), 7.28 (d, J = 8.5 Hz, 2H), 6.82 (s, 1H), 6.75 (d, J = 7.6 Hz, 1H), 5.00 (dd, J = 13.2, 5.0 Hz, 1H), 4.37 (d, J = 4.3 Hz, 1H), 4.27 (dd, J = 16.9, 3.5 Hz, 1H), 4.13 (dd, J = 16.9, 2.5 Hz, 1H), 3.75 (s, 1H), 3.32 - 3.21 (m, 2H), 2.95 - 2.73 (m, 3H), 2.57 (d, J = 17.3 Hz, 2H), 2.41 - 2.27 (m, 3H), 2.24 - 2.18 (m, 1H), 2.00 - 1.88 (m, 2H), 1.78 (brs, 1H), 1.65 (brs, 1H), 1.51 - 1.43 (m, 2H), 1.27 - 1.16 (m, 1H), 0.99 (d, J = 4.2 Hz, 6H). LCMS (ESI) calcd. for C34H39ClN5O4+ [M+H]+: 616.27, found, 616.3.

[0557] Example 143: Preparation of compound GT-09982

[0558] With reference to the method of Scheme 3, the target compound GT-09982 was obtained (18 mg, white solid, yield 34%). 1H NMR (400 MHz, DMSO-d6) 8 10.93 (s, 1H), 7.43 - 7.36 (m, 3H), 7.28 (d, J = 8.4 Hz, 2H), 6.85 (s, 1H), 6.77 (d, J = 8.3 Hz, 1H), 5.01 (dd, J = 13.4, 5.1 Hz, 1H), 4.28 (d, J = 16.8 Hz, 1H), 4.14 (d, J = 16.9 Hz, 1H), 3.25 - 3.15 (m, 3H), 2.94 - 2.85 (m, 1H), 2.58 (d, J = 17.7 Hz, 2H), 2.35 - 2.24 (m, 5H), 2.14 (s, 3H), 2.01 - 1.86 (m, 1H), 1.43 - 1.40 (m, 5H), 1.35 - 1.19 (m, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C35H41ClN5O4+ [M+H]+: 630.28, found, 630.3.

[0559] Example 144: Preparation of compound GT-09983

[0560] With reference to the method of Scheme 3, the target compound GT-09983 was obtained (19 mg, white solid, yield 35%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.44 - 7.36 (m, 3H), 7.32 - 7.25 (m, 2H), 6.84 (d, J = 6.5 Hz, 1H), 6.76 (t, J = 8.1 Hz, 1H), 5.01 (dd, J = 13.2, 5.0 Hz, 1H), 4.28 (d, J = 16.8 Hz, 1H), 4.14 (d, J = 16.8 Hz, 1H), 3.34 - 3.18 (m, 3H), 3.03 - 2.83 (m, 2H), 2.80 - 2.65 (m, 2H), 2.58 (d, J = 15.9 Hz, 2H), 2.39 - 2.32 (m, 4H), 2.23 - 2.08 (m, 1H), 1.95 - 1.91 (m, 2H), 1.74 (brs, 1H), 1.65 - 1.51 (m, 1H), 1.51 - 1.37 (m, 2H), 0.99 (s, 6H). LCMS (ESI) calcd. for C33H39ClN5O4+ [M+H]+: 604.27, found, 604.3.

[0561] Example 145: Preparation of compound GT-09984

[0562] With reference to the method of Scheme 3, the target compound GT-09984 was obtained (37 mg, white solid, yield 68%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.43 - 7.40 (m, 3H), 7.29 (d, J = 8.5 Hz, 2H), 6.83 (s, 1H), 6.77 (d, J = 8.4 Hz, 1H), 5.01 (dd, J = 13.2, 5.1 Hz, 1H), 4.27 (d, J = 17.0 Hz, 1H), 4.13 (d, J = 16.8 Hz, 1H), 3.99 (s, 1H), 3.67 (s, 1H), 3.34 - 2.99 (m, 3H), 2.89 - 2.84 (m, 1H), 2.57 (d, J = 19.2 Hz, 2H), 2.41 - 2.18 (m, 4H), 2.00 - 1.85 (m, 3H), 1.48 - 1.41 (m, 2H), 1.29 (brs, 1H), 0.96 (d, J = 3.3 Hz, 6H). LCMS (ESI) calcd. for C33H37ClN5O4+ [M+H]+: 602.25, found, 602.3.

[0563] Example 146: Preparation of compound GT-09985

[0564] With reference to the method of Scheme 3, the target compound GT-09985 was obtained (36 mg, white solid, yield 66%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.50 - 7.32 (m, 4H), 7.28 (d, J = 8.4 Hz, 1H), 6.88 (s, 1H), 6.79 (d, J = 8.0 Hz, 1H), 5.01 (dd, J = 13.0, 4.7 Hz, 1H), 4.27 (d, J = 17.1 Hz, 1H), 4.14 (d, J = 16.7 Hz, 1H), 3.40 - 3.22 (m, 4H), 2.99 - 2.81 (m, 2H), 2.65 - 2.52 (m, 2H), 2.43 - 2.29 (m, 3H), 2.28 - 2.13 (m, 2H), 2.01 - 1.85 (m, 2H), 1.76 - 1.65 (m, 1H), 1.50 - 1.39 (m, 2H), 0.99 (s, 6H). LCMS (ESI) calcd. for C33H37ClN5O4+ [M+H]+: 602.25, found, 602.3.

[0565] Example 147: Preparation of compound GT-09986

[0566] With reference to the method of Scheme 3, the target compound GT-09986 was obtained (25 mg, white solid, yield 46%). 1H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 7.46 - 7.34 (m, 4H), 7.21 (d, J = 8.0 Hz, 1H), 7.02 - 6.82 (m, 2H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.28 (d, J = 16.7 Hz, 1H), 4.13 (d, J = 16.8 Hz, 1H), 3.36 - 3.24 (m, 2H), 3.24 - 3.08 (m, 2H), 3.00 (s, 1H), 2.95 - 2.81 (m, 1H), 2.58 (d, J = 16.4 Hz, 2H), 2.38 - 2.28 (m, 4H), 2.20 - 2.06 (m, 1H), 2.03 -1.88 (m, 3H), 1.72 (brs, 1H), 1.52 - 1.34 (m, 3H), 0.98 (d, J = 14.1 Hz, 6H). LCMS (ESI) calcd. for C34H39ClN5O4+ [M+H]+: 616.27, found, 616.3.

[0567] Example 148: Preparation of compound GT-09987

[0568] With reference to the method of Scheme 3, the target compound GT-09987 was obtained (25 mg, white solid, yield 47%). 1H NMR (400 MHz, DMSO-d6) 8 10.94 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.36 - 7.25 (m, 2H), 7.17 (t, J = 7.9 Hz, 2H), 6.87 - 6.61 (m, 2H), 5.03 (dd, J = 13.2, 5.0 Hz, 1H), 4.30 (d, J = 17.0 Hz, 1H), 4.16 (d, J = 16.9 Hz, 1H), 3.38 - 3.31 (m, 5H), 2.98 - 2.84 (m, 2H), 2.60 - 2.51 (m, 4H), 2.44 - 2.20 (m, 5H), 2.05 - 1.88 (m, 2H), 1.45 (t, J = 6.0 Hz, 2H), 0.99 (s, 6H). LCMS (ESI) calcd. for C34H39FN5O4+ [M+H]+: 600.30, found, 600.4.

[0569] Example 149: Preparation of compound GT-09988

[0570] With reference to the method of Scheme 3, the target compound GT-09988 was obtained (32 mg, white solid, yield 61%). 1H NMR (400 MHz, DMSO-d6) 8 10.92 (s, 1H), 7.41 (d, J = 8.3 Hz, 1H), 7.30 (dd, J = 8.5, 5.7 Hz, 2H), 7.16 (t, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.75 (d, J = 8.2 Hz, 1H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (s, 1H), 4.27 (dd, J = 16.9, 3.6 Hz, 1H), 4.13 (dd, J = 17.0, 2.6 Hz, 1H), 3.76 (s, 1H), 2.89 - 2.83 (m, 1H), 2.80 (d, J = 9.8 Hz, 2H), 2.59 - 2.52 (m, 3H), 2.46 - 2.39 (m, 2H), 2.39 - 2.27 (m, 2H), 2.26 - 2.13 (m, 1H), 2.01 - 1.86 (m, 2H), 1.77 (brs, 1H), 1.64 (brs, 1H), 1.54 - 1.39 (m, 2H), 1.20 - 1.16 (m, 1H), 0.99 (d, J = 3.8 Hz, 6H). LCMS (ESI) calcd. for C34H39FN5O4+ [M+H]+: 600.30, found, 600.4.

[0571] Example 150: Preparation of compound GT-09989

[0572] With reference to the method of Scheme 3, the target compound GT-09989 was obtained (28 mg, white solid, yield 54%). 1H NMR (400 MHz, DMSO-d6) 8 10.93 (s, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.30 (dd, J = 8.7, 5.6 Hz, 2H), 7.18 (t, J = 8.9 Hz, 2H), 6.88 (s, 1H), 6.80 (d, J = 8.4 Hz, 1H), 5.01 (dd, J = 13.2, 5.1 Hz, 1H), 4.28 (d, J = 17.0 Hz, 1H), 4.15 (d, J = 16.9 Hz, 1H), 3.45 -3.37 (m, 4H), 3.32 (s, 2H), 3.22 (s, 2H), 2.94 - 2.85 (m, 1H), 2.58 (d, J = 16.5 Hz, 2H), 2.33 (dd, J = 12.9, 4.5 Hz, 1H), 2.26 (brs, 2H), 2.13 (s, 2H), 1.99 - 1.87 (m, 1H), 1.50 - 1.39 (m, 4H), 1.33 (brs, 1H), 0.98 (s, 6H). LCMS (ESI) calcd. for C35H41FN5O4+ [M+H]+: 614.31, found, 614.4.

[0573] Example 151: Preparation of compound GT-09990

[0574] With reference to the method of Scheme 3, the target compound GT-09990 was obtained (26 mg, white solid, yield 49%). 1H NMR (400 MHz, DMSO-d6) 8 10.93 (s, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.33 - 7.28 (m, 2H), 7.19 - 7.13 (m, 2H), 6.84 (d, J = 8.6 Hz, 1H), 6.78 (d, J = 9.3 Hz, 1H), 5.01 (dd, J = 13.3, 4.9 Hz, 1H), 4.28 (d, J = 16.8 Hz, 1H), 4.14 (d, J = 16.8 Hz, 1H), 3.34 -3.26 (m, 2H), 3.00 - 2.89 (m, 1H), 2.83 - 2.66 (m, 2H), 2.62 - 2.55 (m, 4H), 2.44 - 2.28 (m, 4H), 2.19 - 2.12 (m, 1H), 2.02 - 1.85 (m, 2H), 1.75 (brs, 1H), 1.63 - 1.36 (m, 3H), 0.98 (s, 6H). LCMS (ESI) calcd. for C33H39FN5O4+ [M+H]+: 588.30, found, 588.3.

[0575] Example 152: Preparation of compound GT-09991

[0576] With reference to the method of Scheme 3, the target compound GT-09991 was obtained (29 mg, white solid, yield 55%). 1H NMR (400 MHz, DMSO-d6) 8 10.92 (s, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.30 (dd, J = 8.7, 5.6 Hz, 2H), 7.19 (t, J = 8.9 Hz, 2H), 6.83 (s, 1H), 6.77 (d, J = 8.3 Hz, 1H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.27 (d, J = 16.9 Hz, 1H), 4.13 (d, J = 16.9 Hz, 1H), 3.98 (s, 1H), 3.67 (s, 1H), 3.24 (brs, 2H), 3.18 - 2.98 (m, 2H), 2.96 - 2.83 (m, 1H), 2.57 (d, J = 17.8 Hz, 2H), 2.41 - 2.29 (m, 2H), 2.29 - 2.16 (m, 1H), 1.98 - 1.83 (m, 3H), 1.47 - 1.41 (m, 2H), 1.30 (s, 1H), 0.96 (d, J = 3.2 Hz, 6H). LCMS (ESI) calcd. for C33H37FN5O4+ [M+H]+: 586.28, found, 586.3.

[0577] Example 153: Preparation of compound GT-09994

[0578] With reference to the method of Scheme 3, the target compound GT-09994 was obtained (33 mg, white solid, yield 62%). 1H NMR (400 MHz, DMSO-d6) 8 10.93 (s, 1H), 7.45 - 7.34 (m, 2H), 7.32 - 7.28 (m, 1H), 7.24 (t, J = 8.7 Hz, 1H), 7.17 (t, J = 8.8 Hz, 1H), 6.88 (s, 1H), 6.79 (d, J = 7.9 Hz, 1H), 5.09 - 4.96 (m, 1H), 4.27 (d, J = 15.1 Hz, 1H), 4.14 (d, J = 16.7 Hz, 1H), 3.32 -3.23 (m, 5H), 3.01 - 2.80 (m, 2H), 2.74 - 2.62 (m, 2H), 2.41 - 2.32 (m, 3H), 2.28 - 2.13 (m, 2H), 2.02 - 1.83 (m, 2H), 1.53 - 1.38 (m, 2H), 1.00 (d, J = 1.6 Hz, 6H) LCMS (ESI) calcd. for C33H37FN5O4+ [M+H]+: 586.28, found, 586.3.

[0579] Example 154: Preparation of compound GT-09992

[0580] With reference to the method of Scheme 2, the target compound GT-09992 was obtained (73 mg, white solid, yield 77%). 1H NMR (400 MHz, DMSO-d6) 8 10.95 (s, 1H), 9.42 (d, J = 13.9 Hz, 1H), 8.97 (d, J = 13.9 Hz, 1H), 8.24 - 8.21 (m, 3H), 7.63 - 7.51 (m, 4H), 7.44 (d, J = 8.5 Hz, 1H), 6.95 (s, 2H), 5.01 (dd, J = 13.3, 5.1 Hz, 1H), 4.76 (d, J = 3.5 Hz, 1H), 4.66 (d, J = 19.9 Hz, 1H), 4.26 (d, J = 16.9 Hz, 1H), 4.13 (d, J = 16.6 Hz, 1H), 3.59 - 3.44 (m, 2H), 3.15 - 2.83 (m, 7H), 2.68 - 2.56 (m, 3H), 2.26 (dd, J = 13.1, 4.3 Hz, 1H), 1.99 - 1.87 (m, 1H). LCMS (ESI) calcd. for C30H32N7O3+ [M+H]+: 538.26, found, 538.3.

[0581] Example 155: Preparation of compound GT-09993

[0582] With reference to the method of Scheme 2, the target compound GT-09993 was obtained (33 mg, white solid, yield 68%). 1H NMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 9.37 (s, 1H), 9.00 (s, 1H), 8.21 (dd, J = 7.9, 1.5 Hz, 2H), 7.61 - 7.56 (m, 3H), 7.48 (d, J = 8.3 Hz, 1H), 6.99 (s, 1H), 6.91 (d, J = 8.1 Hz, 1H), 5.03 (dd, J = 13.3, 5.0 Hz, 1H), 4.50 (s, 2H), 4.33 (d, J = 16.9 Hz, 1H), 4.21 (d, J = 16.9 Hz, 1H)), 4.17 (s, 2H), 3.23 - 3.10 (m, 2H), 3.01 (d, J = 11.7 Hz, 2H), 2.96 - 2.84 (m, 1H), 2.60 (d, J = 17.4 Hz, 2H), 2.45 - 2.25 (m, 5H), 2.01 - 1.95 (m, 1H). LCMS (ESI) calcd. for C30H32N7O3+ [M+H]+: 538.26, found, 538.3.

[0583] Example 156: Preparation of compound GT-10026

[0584] With reference to the method of Scheme 2, the target compound GT-10026 was obtained (15 mg, white solid, yield 32%). 1H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 9.30 (d, J = 1.2 Hz, 1H), 8.87 (d, J = 1.2 Hz, 1H), 8.19 (dd, J = 7.7, 1.5 Hz, 2H), 7.59 - 7.54 (m, 3H), 7.47 (d, J = 8.3 Hz, 1H), 7.02 (s, 1H), 6.93 (d, J = 7.7 Hz, 1H), 5.03 (dd, J = 13.3, 5.0 Hz, 1H), 4.72 (d, J = 5.8 Hz, 2H), 4.31 (d, J = 17.0 Hz, 1H), 4.18 (d, J = 16.9 Hz, 1H), 4.13 - 4.00 (m, 4H), 2.97 - 2.84 (m, 2H), 2.58 (d, J = 17.3 Hz, 2H), 2.38 - 2.30 (m, 2H), 2.13 - 1.99 (m, 2H), 2.00 - 1.88 (m, 2H). LCMS (ESI) calcd. for C31H34N7O3+ [M+H]+: 552.27, found, 552.3.

[0585] Example 157: Preparation of compound GT-10028

[0586] With reference to the method of Scheme 2, the target compound GT-10028 was obtained (23 mg, white solid, yield 48%). 1H NMR (400 MHz, DMSO-d6) 5 11.19 (s, 1H), 10.93 (s, 1H), 9.36 (d, J = 1.2 Hz, 1H), 9.02 (d, J = 1.2 Hz, 1H), 8.21 (dd, J = 7.7, 1.6 Hz, 2H), 7.59 - 7.55 (m, 3H), 7.45 (d, J = 8.4 Hz, 1H), 6.95 (s, 1H), 6.88 (d, J = 8.1 Hz, 1H), 5.02 (dd, J = 13.3, 5.1 Hz, 1H), 4.66 (s, 2H), 4.29 (d, J = 16.9 Hz, 1H), 4.16 (d, J = 16.9 Hz, 1H), 3.51 - 3.41 (m, 4H), 3.31 - 3.25 (m, 1H), 3.18 - 3.14 (m, 1H), 3.08 - 2.96 (m, 1H), 2.96 - 2.83 (m, 1H), 2.58 (d, J = 17.2 Hz, 2H), 2.40 - 2.29 (m, 1H), 2.10 (brs, 2H), 2.00 - 1.86 (m, 1H) LCMS (ESI) calcd. for C29H32N7O3+ [M+H]+: 526.26, found, 526.3.

[0587] Example 158: Preparation of compound GT-10029

[0588] With reference to the method of Scheme 2, the target compound GT-10029 was obtained (26 mg, white solid, yield 55%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 9.36 (d, J = 1.2 Hz, 1H), 9.02 (d, J = 1.2 Hz, 1H), 8.21 (dd, J = 7.7, 1.6 Hz, 2H), 7.59 - 7.55 (m, 3H), 7.45 (d, J = 8.4 Hz, 1H), 6.95 (s, 1H), 6.88 (d, J = 8.1 Hz, 1H), 5.03 (dd, J = 13.3, 5.0 Hz, 1H), 4.88 - 4.76 (m, 1H), 4.59 - 4.45 (m, 2H), 4.31 (d, J = 17.0 Hz, 1H), 4.18 (d, J = 16.4 Hz, 1H), 3.80 (s, 1H), 3.71 - 3.53 (m, 2H), 3.34 - 3.25 (m, 2H), 2.97 - 2.82 (m, 2H), 2.59 (d, J = 17.1 Hz, 2H), 2.40 - 2.21 (m, 1H), 2.00 - 1.89 (m, 1H). LCMS (ESI) calcd. for C29H30N7O3+ [M+H]+: 524.24, found, 524.3.

[0589] Example 159: Preparation of compound GT-10056

[0590] With reference to the method of Scheme 2, the target compound GT-10056 was obtained (23 mg, white solid, yield 48%). 1H NMR (400 MHz, DMSO-d6) 8 11.06 (s, 1H), 8.04 (s, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.57 - 7.51 (m, 3H), 7.48 (d, J = 5.9 Hz, 1H), 7.46 - 7.41 (m, 2H), 7.38 (d, J = 6.4 Hz, 1H), 7.14 (s, 1H), 7.01 (d, J = 8.2 Hz, 1H), 5.03 (dd, J = 12.8, 5.4 Hz, 1H), 3.45 -3.38 (m, 2H), 3.34 - 3.26 (m, 4H), 3.26 - 3.15 (m, 2H), 2.91 - 2.78 (m, 2H), 2.59 (s, 1H), 2.61 -2.58 (m, 1H), 2.49 - 2.39 (m, 2H), 2.01 - 1.95 (m, 1H). LCMS (ESI) calcd. for C29H30N7O3+ [M+H]+: 524.24, found, 524.3.

[0591] Example 160: Preparation of compound GT-10057

[0592] With reference to the method of Scheme 3, the target compound GT-10057 was obtained (11 mg, white solid, yield 21%). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 8.11 (s, 1H), 7.54 (dd, J = 8.3, 2.6 Hz, 4H), 7.48 (t, J = 6.9 Hz, 2H), 7.42 (d, J = 8.3 Hz, 2H), 7.37 (t, J = 7.1 Hz, 2H), 5.04 (dd, J = 12.7, 5.4 Hz, 1H), 3.43 - 3.40 (m, 2H), 3.26 - 3.19 (m, 2H), 2.91 - 2.82 (m, 2H), 2.79 - 2.70 (m, 1H), 2.57 (d, J = 21.0 Hz, 2H), 2.48 - 2.37 (m, 2H), 2.06 - 1.93 (m, 1H). LCMS (ESI) calcd. for C30H26ClFN5O5+ [M+H]+: 590.16, found, 590.2.

[0593] Example 161: Preparation of compound GT-10058

[0594] With reference to the method of Scheme 3, the target compound GT-10058 was obtained (6 mg, white solid, yield 12%). 1H NMR (400 MHz, DMSO-d6) 8 11.07 (s, 1H), 8.42 (s, 1H), 7.56 - 7.51 (m, 4H), 7.48 - 7.44 (m, 2H), 7.38 (d, J = 7.4 Hz, 2H), 6.96 (s, 1H), 6.75 (s, 1H), 5.03 (dd, J = 12.8, 5.4 Hz, 1H), 3.44 - 3.40 (m, 2H), 3.26 - 3.14 (m, 2H), 3.10 - 2.89 (m, 2H), 2.88 - 2.79 (m, 1H), 2.59 - 2.56 (m, 2H), 2.48 - 2.36 (m, 2H), 2.02 - 1.95 (m, 1H). LCMS (ESI) calcd. for C30H26ClFN5O5+ [M+H]+: 590.16, found, 590.2.

[0595] Example 162: Preparation of compound GT-10059

[0596] With reference to the method of Scheme 3, the target compound GT-10059 was obtained (7 mg, white solid, yield 13%). 1H NMR (400 MHz, DMSO-d6) 8 11.09 (s, 1H), 8.07 (s, 1H), 7.52 (d, J = 8.2 Hz, 1H), 7.41 - 7.35 (m, 3H), 7.24 (d, J = 8.4 Hz, 2H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 3.31 - 3.15 (m, 4H), 2.94 - 2.81 (m, 2H), 2.60 - 2.55 (m, 2H), 2.40 - 2.21 (m, 3H), 2.21 - 2.06 (m, 2H), 2.06 - 1.85 (m, 3H), 1.57 - 1.38 (m, 2H), 0.99 (d, J = 9.2 Hz, 6H). LCMS (ESI) calcd. for C32H34ClFN5O5+ [M+H]+: 622.22, found, 622.3.

[0597] Example 163: Preparation of compound GT-10060

[0598] With reference to the method of Scheme 3, the target compound GT-10060 was obtained (14 mg, white solid, yield 26%). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 8.37 (s, 1H), 7.40 (d, J = 8.5 Hz, 2H), 7.28 - 7.24 (m, 2H), 6.94 (s, 1H), 6.75 (s, 1H), 5.03 (dd, J = 12.7, 5.4 Hz, 1H), 3.31 - 3.13 (m, 4H), 3.01 - 2.74 (m, 3H), 2.57 (d, J = 18.6 Hz, 2H), 2.37 - 2.33 (m, 3H), 2.22 - 2.06 (m, 1H), 2.04 - 1.78 (m, 3H), 1.51 - 1.41 (m, 2H), 0.98 (d, J = 11.1 Hz, 6H). LCMS (ESI) calcd. for C32H34ClFN5O5+ [M+H]+: 622.22, found, 622.2.

[0599] Example 164: Preparation of compound GT-10061

[0600] With reference to the method of Scheme 1, the target compound GT-10061 was obtained (20 mg, white solid, yield 38%). 1H NMR (400 MHz, DMSO-d6) 8 10.94 (s, 1H), 9.29 (s, 1H), 7.50 (d, J = 7.9 Hz, 2H), 7.44 (d, J = 8.3 Hz, 1H), 7.19 (d, J = 8.1 Hz, 2H), 6.94 (s, 1H), 6.90 (d, J = 8.4 Hz, 1H), 5.03 (dd, J = 13.2, 5.0 Hz, 1H), 4.30 (d, J = 16.8 Hz, 1H), 4.17 (d, J = 17.0 Hz, 1H), 3.61 (s, 2H), 3.28 - 3.11 (m, 3H), 3.03 (brs, 2H), 2.97 - 2.84 (m, 2H), 2.59 (d, J = 17.7 Hz, 2H), 2.36 - 2.31 (m, 2H), 2.13 (s, 4H), 2.02 (d, J = 17.3 Hz, 2H), 2.01 - 1.88 (m, 2H), 1.48 (s, 2H), 0.97 (s, 6H). LCMS (ESI) calcd. for C34H41ClN5O3+ [M+H]+: 602.29, found, 602.4.

[0601] Example 165: Preparation of compound GT-10062

[0602] With reference to the method of Scheme 1, the target compound GT-10062 was obtained (9 mg, white solid, yield 17%). 1H NMR (400 MHz, DMSO-d6) 8 11.09 (s, 1H), 8.43 (s, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.47 - 7.43 (m, 3H), 7.16 (d, J = 9.2 Hz, 2H), 5.05 (dd, J = 12.7, 5.4 Hz, 1H), 3.60 (s, 2H), 3.18 - 3.13 (m, 3H), 3.05 - 2.81 (m, 5H), 2.55 (d, J = 4.7 Hz, 2H), 2.38 - 2.27 (m, 2H), 2.10 - 1.93 (m, 4H), 1.54 - 1.42 (m, 2H), 0.97 (s, 6H) LCMS (ESI) calcd. for C32H36ClFN5O4+ [M+H]+: 608.24, found, 608.3.

[0603] Example 166: Preparation of compound GT-10063

[0604] With reference to the method of Scheme 1, the target compound GT-10063 was obtained (12 mg, white solid, yield 23%). 1H NMR (400 MHz, DMSO-d6) 8 11.08 (s, 1H), 9.97 (s, 1H), 8.81 (s, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 7.00 (s, 1H), 6.82 (s, 1H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 3.61 (s, 2H), 3.19 - 3.06 (m, 2H), 3.06 - 2.93 (m, 4H), 2.92 - 2.78 (m, 2H), 2.55 (d, J = 4.8 Hz, 2H), 2.33 (s, 2H), 2.10 - 1.95 (m, 4H), 1.47 (t, J = 6.6 Hz, 2H), 0.97 (s, 6H). LCMS (ESI) calcd. for C32H36ClFN5O4+ [M+H]+: 608.24, found, 608.3.

[0605] Example 167: Preparation of compound GT-10065

[0606] With reference to the method of Scheme 1, the target compound GT-10065 was obtained (17 mg, white solid, yield 32%). 1H NMR (400 MHz, DMSO-d6) 8 10.97 (s, 1H), 7.52 - 7.46 (m, 2H), 7.46 - 7.41 (m, 1H), 7.21 (d, J = 8.4 Hz, 2H), 7.17 (s, 1H), 6.69 (d, J = 8.1 Hz, 1H), 5.06 (dd, J = 13.1, 5.1 Hz, 1H), 4.30 (d, J = 16.7 Hz, 1H), 4.18 (d, J = 16.6 Hz, 1H), 3.76 - 3.60 (m, 3H), 3.00 - 2.80 (m, 5H), 2.65 - 2.55 (m, 2H), 2.45 - 2.41 (m, 2H), 2.33 - 2.27 (m, 4H), 2.05 (s, 2H), 2.02 - 1.97 (m, 2H), 1.48 (t, J = 6.3 Hz, 3H), 0.98 (s, 6H). LCMS (ESI) calcd. for C34H41ClN5O3+ [M+H]+: 602.29, found, 602.4.

[0607] Example 168: Preparation of compound GT-10066

[0608] With reference to the method of Scheme 1, the target compound GT-10066 was obtained (14 mg, white solid, yield 26%). 1H NMR (400 MHz, DMSO-d6) 8 10.93 (s, 1H), 7.48 - 7.43 (m, 4H), 7.23 (d, J = 8.3 Hz, 2H), 6.93 (s, 1H), 5.02 (dd, J = 13.2, 4.9 Hz, 1H), 4.28 (d, J = 17.0 Hz, 1H), 4.15 (d, J = 17.0 Hz, 1H), 3.79 (s, 2H), 3.55 (d, J = 4.8 Hz, 2H), 3.19 (d, J = 11.4 Hz, 2H), 2.92 - 2.87 (m, 2H), 2.63 - 2.54 (m, 2H), 2.41 - 2.31 (m, 3H), 2.10 (s, 2H), 2.04 - 1.91 (m, 3H), 1.50 (t, J = 5.9 Hz, 2H), 1.31 - 1.25 (m, 2H), 0.98 (s, 6H). LCMS (ESI) calcd. for C34H41ClN5O3+ [M+H]+: 602.29, found, 602.3.

[0609] Example 169: Preparation of compound GT-10067

[0610] With reference to the method of Scheme 1, the target compound GT-10067 was obtained (16 mg, white solid, yield 31%). 1H NMR (400 MHz, DMSO-d6) 8 10.93 (s, 1H), 7.47 - 7.42 (m, 3H), 7.21 (d, J = 8.3 Hz, 2H), 6.88 (s, 1H), 6.81 (d, J = 7.5 Hz, 1H), 5.02 (dd, J = 13.3, 5.1 Hz, 1H), 4.29 (d, J = 17.0 Hz, 1H), 4.15 (d, J = 16.9 Hz, 1H), 4.00 - 3.87 (m, 2H), 3.67 (d, J = 5.6 Hz, 2H), 3.63 - 3.50 (m, 4H), 3.35 - 3.24 (m, 2H), 2.97 - 2.84 (m, 1H), 2.60 (s, 1H), 2.55 - 2.51 (m, 2H), 2.37 - 2.30 (m, 1H), 2.18 (brs, 2H), 2.05 (brs, 2H), 1.99 - 1.87 (m, 2H), 1. 63 - 1.56(m, 1H), 1.50 - 1.38 (m, 2H), 0.96 (s, 6H). LCMS (ESI) calcd. for C35H43ClN5O3+ [M+H]+: 616.30, found, 616.4.

[0611] Example 170: Preparation of compound GT-10068

[0612] With reference to the method of Scheme 1, the target compound GT-10068 was obtained (14 mg, white solid, yield 26%). 1H NMR (400 MHz, DMSO-d6) 8 10.94 (s, 1H), 9.93 (s, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.3 Hz, 1H), 7.17 (d, J = 8.4 Hz, 2H), 6.86 (s, 1H), 6.79 (d, J = 7.9 Hz, 1H), 5.02 (dd, J = 13.1, 5.2 Hz, 1H), 4.29 (d, J = 16.8 Hz, 1H), 4.15 (d, J = 16.8 Hz, 1H), 3.60 (s, 2H), 3.18 - 3.02 (m, 3H), 2.93 - 2.80 (m, 4H), 2.59 (d, J = 17.4 Hz, 2H), 2.40 - 2.22 (m, 4H), 2.05 (s, 2H), 2.00 - 1.83 (m, 2H), 1.78 - 1.65 (m, 1H), 1.47 (t, J = 6.2 Hz, 2H), 0.96 (s, 6H). LCMS (ESI) calcd. for C33H41ClN5O3+ [M+H]+: 590.29, found, 590.3.

[0613] Example 171: Preparation of compound GT-10069

[0614] With reference to the method of Scheme 1, the target compound GT-10069 was obtained (16 mg, white solid, yield 30%). 1H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 7.72 (s, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 1H), 6.93 (s, 1H), 6.84 (d, J = 7.5 Hz, 1H), 5.03 (dd, J = 12.6, 5.7 Hz, 1H), 4.30 (d, J = 16.8 Hz, 1H), 4.16 (d, J = 17.0 Hz, 1H), 3.71 - 3.66 (m, 1H), 3.55 - 3.43 (m, 2H), 3.32 - 3.13 (m, 4H), 3.01 - 2.84 (m, 2H), 2.63 - 2.53 (m, 2H), 2.44 - 2.20 (m, 4H), 2.13 - 2.01 (m, 2H), 2.01 - 1.93 (m, 1H), 1.51 - 1.41 (m, 2H), 0.99 (s, 3H), 0.97 (s, 3H). LCMS (ESI) calcd. for C33H39ClN5O3+ [M+H]+: 588.27, found, 588.3.

[0615] Example 172: Preparation of compound GT-10070

[0616] With reference to the method of Scheme 3, the target compound GT-10070 was obtained (14 mg, white solid, yield 28%). 1H NMR (400 MHz, DMSO-d6) 5 11.07 (s, 1H), 8.69 (d, J = 7.7 Hz, 1H), 8.17 (d, J = 7.9 Hz, 1H), 8.07 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.22 (s, 1H), 7.08 (s, 1H), 5.05 (dd, J = 13.0, 5.3 Hz, 1H), 4.74 (s, 1H), 4.42 - 4.10 (m, 1H), 3.81 (brs, 2H), 3.76 - 3.65 (m, 2H), 3.56 (s, 4H), 3.13 - 2.95 (m, 2H), 2.97 - 2.85 (m, 2H), 2.58 (d, J = 16.2 Hz, 2H), 2.07 - 1.87 (m, 4H). LCMS (ESI) calcd. for C29H30N9O6+ [M+H]+: 600.23, found, 600.3.

[0617] Example 173: Preparation of compound GT-10124

[0618] With reference to the method of Scheme 2, the target compound GT-10124 was obtained (15 mg, white solid, yield 31%). 1H NMR (400 MHz, DMSO-d6) 5 9.11 (s, 1H), 9.02 - 8.95 (m, 3H), 8.89 - 8.84 (m, 2H), 8.47 (d, J = 8.1 Hz, 1H), 8.40 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 7.8 Hz, 1H), 5.10 (dd, J = 13.3, 5.1 Hz, 1H), 4.75 (s, 2H), 4.48 - 4.41 (m, 2H), 3.90 (s, 1H), 3.75 - 3.52 (m, 4H), 3.22 - 3.17 (m, 2H), 2.93 - 2.82 (m, 2H), 2.82 - 2.72 (m, 1H), 2.50 - 2.31 (m, 3H), 2.20 - 2.10 (m, 1H). LCMS (ESI) calcd. for C30H32N7O3+ [M+H]+: 538.26, found, 538.3.

[0619] Example 174: Preparation of compound GT-10125

[0620] With reference to the method of Scheme 2, the target compound GT-10125 was obtained (19 mg, white solid, yield 40%). 1H NMR (400 MHz, DMSO-d6) 5 9.13 (s, 1H), 9.00 (d, J = 6.9 Hz, 2H), 8.85 (d, J = 6.9 Hz, 2H), 8.47 (d, J = 1.3 Hz, 2H), 7.57 (d, J = 8.4 Hz, 1H), 7.02 (s, 1H), 6.95 (d, J = 8.2 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.51 (s, 2H), 4.38 (d, J = 9.0 Hz, 2H), 4.10 (s, 3H), 3.23 (d, J = 12.3 Hz, 2H), 3.19 - 3.08 (m, 3H), 2.94 (d, J = 12.3 Hz, 1H), 2.87 (dd, J = 13.3, 5.3 Hz, 1H), 2.80 - 2.73 (m, 1H), 2.39 - 2.33 (m, 1H), 2.18 - 2.09 (m, 2H). LCMS (ESI) calcd. for C30H32N7O3+ [M+H]+: 538.26, found, 538.3.

[0621] Example 175: Preparation of compound GT-10126

[0622] With reference to the method of Scheme 2, the target compound GT-10126 was obtained (15 mg, white solid, yield 32%). 1H NMR (400 MHz, DMSO-d6) 8 9.06 (d, J = 1.9 Hz, 1H), 8.99 (d, J = 6.9 Hz, 2H), 8.83 (d, J = 6.9 Hz, 2H), 8.44 (d, J = 8.1 Hz, 1H), 8.35 (dd, J = 8.2, 2.2 Hz, 1H), 7.75 (dd, J = 8.3, 4.3 Hz, 1H), 7.47 (d, J = 7.0 Hz, 1H), 7.33 - 7.29 (m, 1H), 5.13 (dd, J = 13.4, 5.0 Hz, 1H), 4.70 (s, 2H), 4.53 (d, J = 11.5 Hz, 1H), 4.48 (dd, J = 9.8, 2.2 Hz, 2H), 4.32 -4.29 (m, 1H), 4.20 (s, 1H), 4.01 (s, 3H), 3.58 - 3.42 (m, 4H), 2.92 - 2.84 (m, 1H), 2.83 - 2.72 (m, 1H), 2.37 - 2.32 (m, 3H), 2.22 - 2.15 (m, 1H). LCMS (ESI) calcd. for C31H34N7O3+ [M+H]+: 552.27, found, 552.3.

[0623] Example 176: Preparation of compound GT-10127

[0624] With reference to the method of Scheme 2, the target compound GT-10127 was obtained (10 mg, white solid, yield 21%). 1H NMR (400 MHz, DMSO-d6) 8 9.10 (d, J = 1.5 Hz, 1H), 8.99 (d, J = 6.8 Hz, 2H), 8.89 - 8.83 (m, 2H), 8.46 (d, J = 8.2 Hz, 1H), 8.44 - 8.38 (m, 1H), 7.59 - 7.51 (m, 1H), 7.08 (s, 1H), 6.96 (d, J = 8.4 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.67 (s, 2H), 4.38 (d, J = 8.2 Hz, 2H), 3.61 (s, 4H), 3.46 - 3.37 (m, 2H), 3.28 - 3.24 (m, 1H), 3.17 - 3.06 (m, 2H), 2.91 - 2.84 (m, 1H), 2.82 - 2.72 (m, 1H), 2.46 (dd, J = 13.2, 4.7 Hz, 1H), 2.38 (dd, J = 12.3, 6.8 Hz, 1H), 2.14 - 2.07 (m, 1H). LCMS (ESI) calcd. for C29H32N7O3+ [M+H]+: 526.26, found, 526.3.

[0625] Example 177: Preparation of compound GT-10128

[0626] With reference to the method of Scheme 2, the target compound GT-10128 was obtained (13 mg, white solid, yield 27%). 1H NMR (400 MHz, DMSO-d6) 8 9.12 (s, 1H), 8.99 (d, J = 6.8 Hz, 2H), 8.85 (d, J = 6.3 Hz, 2H), 8.46 (s, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.07 (s, 1H), 6.97 (d, J = 8.5 Hz, 1H), 5.06 (dd, J = 13.3, 5.1 Hz, 1H), 4.59 - 4.51 (m, 1H), 4.43 (t, J = 8.4 Hz, 1H), 4.41 -4.34 (m, 2H), 3.76 (d, J = 10.3 Hz, 1H), 3.70 (d, J = 14.4 Hz, 1H), 3.63 (d, J = 12.9 Hz, 1H), 3.43 (d, J = 11.9 Hz, 1H), 2.92 - 2.85 (m, 2H), 2.82 - 2.65 (m, 2H), 2.51 - 2.44 (m, 3H), 2.20 - 2.09 (m, 1H). LCMS (ESI) calcd. for C29H30N7O3+ [M+H]+: 524.24, found, 524.3.

[0627] Example 178: Preparation of compound GT-10129

[0628] With reference to the method of Scheme 2, the target compound GT-10129 was obtained (11 mg, white solid, yield 23%). 1H NMR (400 MHz, DMSO-d6) 8 9.12 (s, 1H), 8.99 (d, J = 6.8 Hz, 2H), 8.85 (d, J = 6.3 Hz, 2H), 8.46 (s, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.07 (s, 1H), 6.97 (d, J = 8.5 Hz, 1H), 5.08 (dd, J = 13.3, 5.1 Hz, 1H), 4.42 (s, 2H), 4.40 - 4.30 (m, 4H), 3.77 (s, 1H), 2.87 (dd, J = 13.4, 5.2 Hz, 1H), 2.82 - 2.73 (m, 1H), 2.54 - 2.41 (m, 3H), 2.39 - 2.31 (m, 2H), 2.20 -2.09 (m, 2H). LCMS (ESI) calcd. for C29H30N7O3+ [M+H]+: 524.24, found, 524.3.

[0629] Example 179: Preparation of compound GT-10130

[0630] With reference to the method of Scheme 1, the target compound GT-10130 was obtained (10 mg, white solid, yield 20%). 1H NMR (400 MHz, DMSO-d6) 8 7.79 (d, J = 8.3 Hz, 2H), 7.71 - 7.63 (m, 4H), 7.55 (d, J = 8.9 Hz, 1H), 7.48 (d, J = 8.5 Hz, 2H), 6.95 - 6.91 (m, 2H), 5.03 (dd, J = 13.3, 5.1 Hz, 1H), 4.56 (s, 2H), 4.31 (s, 2H), 3.87 - 3.82 (m, 2H), 3.13 - 3.05 (m, 4H), 3.01 2.98 (m, 2H), 2.92 - 2.83 (m, 1H), 2.78 (dd, J = 10.1, 7.5 Hz, 1H), 2.72 - 2.57 (m, 1H), 2.36 (dd, J = 13.1, 4.9 Hz, 1H), 2.12 - 2.03 (m, 1H). LCMS (ESI) calcd. for C32H33ClN5O3+ [M+H]+: 570.23, found, 570.3.

[0631] Example 180: Preparation of compound GT-10131

[0632] With reference to the method of Scheme 1, the target compound GT-10131 was obtained (15 mg, white solid, yield 30%). 1H NMR (400 MHz, MeOD) 8 7.78 (d, J = 8.2 Hz, 2H), 7.68 -7.64 (m, 4H), 7.58 (d, J = 8.3 Hz, 1H), 7.48 (d, J = 8.6 Hz, 2H), 7.03 (s, 1H), 6.97 (d, J = 8.8 Hz, 1H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.38 - 4.33 (m, 4H), 4.06 (s, 2H), 3.26 - 3.22 (m, 2H), 3.21 - 3.16 (m, 2H), 3.01 - 2.97 (m, 2H), 2.79 - 2.75 (m, 1H), 2.52 - 2.48 (m, 3H), 2.42 - 2.35 (m, 1H), 2.17 - 2.07 (m, 1H). LCMS (ESI) calcd. for C32H33ClN5O3+ [M+H]+: 570.23, found, 570.3.

[0633] Example 181: Preparation of compound GT-10132

[0634] With reference to the method of Scheme 1, the target compound GT-10132 was obtained (16 mg, white solid, yield 32%). 1H NMR (400 MHz, DMSO-d6) 8 7.75 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.6 Hz, 2H), 7.60 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.6 Hz, 2H), 7.02 (s, 1H), 6.93 (dd, J = 8.4, 1.6 Hz, 1H), 5.08 (dd, J = 13.3, 5.2 Hz, 1H), 4.46 (s, 2H), 4.36 (d, J = 7.5 Hz, 2H), 4.08 (d, J = 10.9 Hz, 2H), 4.01 (d, J = 10.8 Hz, 2H), 2.94 - 2.85 (m, 6H), 2.45 (dd, J = 13.1, 4.7 Hz, 1H), 2.18 - 2.12 (m, 1H), 2.11 - 1.95 (m, 4H). LCMS (ESI) calcd. for C32H35ClN5O3+ [M+H]+: 584.24, found, 584.3.

[0635] Example 182: Preparation of compound GT-10133

[0636] With reference to the method of Scheme 1, the target compound GT-10133 was obtained (24 mg, white solid, yield 47%). 1H NMR (400 MHz, DMSO-d6) 5 7.77 (d, J = 8.3 Hz, 2H), 7.69 - 7.64 (m, 4H), 7.56 (d, J = 8.4 Hz, 1H), 7.51 - 7.44 (m, 2H), 7.01 (s, 1H), 6.94 (d, J = 8.4 Hz, 1H), 5.07 (dd, J = 13.4, 5.1 Hz, 1H), 4.49 (s, 2H), 4.39 - 4.32 (m, 2H), 3.60 - 3.58 (m, 2H), 3.55 - 3.43 (m, 2H), 3.29 - 3.24 (m, 2H), 3.17 - 2.99 (m, 2H), 2.91 - 2.84 (m, 1H), 2.82 - 2.71 (m, 1H), 2.45 - 2.37 (m, 1H), 2.29 - 2.17 (m, 1H), 2.15 - 2.05 (m, 2H). LCMS (ESI) calcd. for C31H33ClN5O3+ [M+H]+: 558.23, found, 558.3.

[0637] Example 183: Preparation of compound GT-10134

[0638] With reference to the method of Scheme 1, the target compound GT-10134 was obtained (21 mg, white solid, yield 42%). 1H NMR (400 MHz, DMSO-d6) 5 7.77 (d, J = 8.2 Hz, 2H), 7.71 - 7.64 (m, 4H), 7.55 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.6 Hz, 2H), 7.03 (s, 1H), 6.95 (d, J = 8.3 Hz, 1H), 5.08 (dd, J = 13.4, 5.1 Hz, 1H), 4.53 (d, J = 13.1 Hz, 1H), 4.43 - 4.28 (m, 4H), 3.80 (s, 1H), 3.65 - 3.55 (m, 1H), 3.34 - 3.31 (m, 2H), 3.17 - 3.05 (m, 1H), 2.93 - 2.83 (m, 1H), 2.82 - 2.69 (m, 1H), 2.51 - 2.44 (m, 1H), 2.41 (s, 2H), 2.20 - 2.09 (m, 1H). LCMS (ESI) calcd. for C31H31ClN5O3+ [M+H]+: 556.21, found, 556.3.

[0639] Example 184: Preparation of compound GT-10135

[0640] With reference to the method of Scheme 1, the target compound GT-10135 was obtained (21 mg, white solid, yield 45%). 1H NMR (400 MHz, DMSO-d6) 5 7.60 - 7.50 (m, 2H), 7.34 (s, 2H), 6.98 - 6.91 (m, 2H), 6.73 (d, J = 3.4 Hz, 1H), 6.53 (dd, J = 3.4, 1.9 Hz, 1H), 5.07 (dd, J = 13.2, 5.1 Hz, 1H), 4.77 (s, 2H), 4.37 - 4.22 (m, 2H), 3.91 - 3.86 (m, 2H), 3.63 - 3.48 (m, 1H), 3.23 - 3.04 (m, 4H), 3.05 - 2.97 (m, 2H), 2.88 (dd, J = 12.9, 4.9 Hz, 1H), 2.82 - 2.72 (m, 1H), 2.69 - 2.63 (m, 1H), 2.41 (dd, J = 13.2, 4.6 Hz, 1H), 2.20 - 2.05 (m, 1H). LCMS (ESI) calcd. for C28H30N5O4S+ [M+H]+: 532.20, found, 532.3.

[0641] Example 185: Preparation of compound GT-10136

[0642] With reference to the method of Scheme 1, the target compound GT-10136 was obtained (16 mg, white solid, yield 34%). 1H NMR (400 MHz, DMSO-d6) 5 7.58 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 1.4 Hz, 1H), 7.35 (d, J = 3.8 Hz, 1H), 7.31 (d, J = 3.7 Hz, 1H), 7.02 (s, 1H), 6.96 (d, J = 8.3 Hz, 1H), 6.71 (d, J = 3.4 Hz, 1H), 6.53 (dd, J = 3.4, 1.9 Hz, 1H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.52 (s, 2H), 4.45 - 4.30 (m, 2H), 4.08 (s, 2H), 3.20 (d, J = 11.2 Hz, 2H), 3.01 (d, J = 12.3 Hz, 2H), 2.91 - 2.83 (m, 1H), 2.81 - 2.69 (m, 1H), 2.50 - 2.37 (m, 5H), 2.18 - 2.12 (m, 1H). LCMS (ESI) calcd. for C28H30N5O4S+ [M+H]+: 532.20, found, 532.3.

[0643] Example 186: Preparation of compound GT-10137

[0644] With reference to the method of Scheme 1, the target compound GT-10137 was obtained (21 mg, white solid, yield 45%). 1H NMR (400 MHz, DMSO-d6) 8 7.59 (d, J = 8.4 Hz, 1H), 7.55 - 7.52 (m, 1H), 7.29 (s, 2H), 7.09 (s, 1H), 6.98 (dd, J = 8.4, 1.6 Hz, 1H), 6.69 (d, J = 3.4 Hz, 1H), 6.53 (dd, J = 3.4, 1.9 Hz, 1H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.65 (s, 2H), 4.38 (q, J = 17.0 Hz, 2H), 4.12 - 4.03 (m, 4H), 2.99 - 2.82 (m, 4H), 2.80 - 2.70 (m, 1H), 2.51 - 2.40 (m, 1H), 2.18 -2.00 (m, 6H). LCMS (ESI) calcd. for C29H32N5O4S+ [M+H]+: 546.22, found, 546.3.

[0645] Example 187: Preparation of compound GT-10138

[0646] With reference to the method of Scheme 1, the target compound GT-10138 was obtained (16 mg, white solid, yield 34%). 1H NMR (400 MHz, DMSO-d6) 8 7.58 - 7.53 (m, 2H), 7.34 (d, J = 3.8 Hz, 1H), 7.31 (d, J = 3.8 Hz, 1H), 7.01 (s, 1H), 6.93 (d, J = 8.3 Hz, 1H), 6.72 (d, J = 3.4 Hz, 1H), 6.53 (dd, J = 3.4, 1.9 Hz, 1H), 5.08 (dd, J = 13.3, 5.2 Hz, 1H), 4.68 (s, 2H), 4.41 - 4.31 (m, 2H), 3.67 - 3.61 (m, 2H), 3.56 - 3.45 (m, 2H), 3.30 - 3.23 (m, 2H), 3.13 - 3.02 (m, 2H), 2.93 - 2.83 (m, 1H), 2.82 - 2.71 (m, 1H), 2.43 - 2.39 (m, 1H), 2.27 - 2.01 (m, 3H). LCMS (ESI) calcd. for C27H30N5O4S+ [M+H]+: 520.20, found, 520.3.

[0647] Example 188: Preparation of compound GT-10139

[0648] With reference to the method of Scheme 1, the target compound GT-10139 was obtained (23 mg, white solid, yield 49%). 1H NMR (400 MHz, DMSO-d6) 8 7.58 - 7.54 (m, 2H), 7.35 (d, J = 3.7 Hz, 1H), 7.30 (d, J = 3.7 Hz, 1H), 7.04 (s, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.71 (d, J = 3.3 Hz, 1H), 6.53 (dd, J = 3.4, 1.8 Hz, 1H), 5.08 (dd, J = 13.2, 5.4 Hz, 1H), 4.71 (d, J = 14.0 Hz, 1H), 4.57 (d, J = 14.1 Hz, 1H), 4.40 - 4.34 (m, 3H), 3.80 (s, 1H), 3.75 (s, 1H), 3.58 - 3.44 (m, 1H), 3.37 (d, J = 9.9 Hz, 1H), 3.21 - 3.09 (m, 1H), 2.86 (dd, J = 13.3, 5.1 Hz, 1H), 2.76 (d, J = 17.3 Hz, 1H), 2.53 - 2.29 (m, 3H), 2.20 - 2.05 (m, 1H). LCMS (ESI) calcd. for C27H28N5O4S+ [M+H]+: 518.19, found, 518.2.

[0649] Example 189: Preparation of compound GT-10141

[0650] With reference to the method of Scheme 1, the target compound GT-10141 was obtained (15 mg, white solid, yield 40%). 1H NMR (400 MHz, DMSO-d6) 8 7.72 (dd, J = 7.0, 2.0 Hz, 1H), 7.63 - 7.59 (m, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.44 (dd, J = 5.2, 1.9 Hz, 1H), 7.41 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 10.3 Hz, 1H), 6.79 (s, 1H), 6.75 (dd, J = 8.4, 1.8 Hz, 1H), 5.12 (dd, J = 13.4, 5.2 Hz, 1H), 4.55 (s, 2H), 4.45 - 4.33 (m, 3H), 3.67 (dd, J = 11.3, 7.9 Hz, 2H), 3.26 - 3.17 (m, 1H), 3.01 (d, J = 9.5 Hz, 1H), 2.87 - 2.83 (m, 1H), 2.83 - 2.75 (m, 1H), 2.74 - 2.64 (m, 3H), 2.61 -2.54 (m, 2H), 2.48 (dd, J = 13.1, 4.7 Hz, 1H), 2.23 - 2.13 (m, 1H). LCMS (ESI) calcd. for C32H33ClN5O3+ [M+H]+: 570.23, found, 570.3.

[0651] Example 190: Preparation of compound GT-10142

[0652] With reference to the method of Scheme 1, the target compound GT-10142 was obtained (19 mg, white solid, yield 51%). 1H NMR (400 MHz, DMSO-d6) 5 7.86 (s, 1H), 7.80 (dt, J = 7.5, 1.5 Hz, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.65 - 7.53 (m, 3H), 7.51 - 7.46 (m, 2H), 6.97 - 6.90 (m, 2H), 5.09 (dd, J = 13.2, 5.2 Hz, 1H), 4.58 (s, 2H), 4.31 (s, 2H), 3.85 (dd, J = 11.0, 7.9 Hz, 2H), 3.16 - 3.04 (m, 4H), 3.02 - 2.94 (m, 2H), 2.88 (dd, J = 13.4, 5.1 Hz, 1H), 2.82 - 2.73 (m, 1H), 2.68 - 2.64 (m, 2H), 2.45 - 2.30 (m, 1H), 2.19 - 2.08 (m, 1H). LCMS (ESI) calcd. for C32H33ClN5O3+ [M+H]+: 570.23, found, 570.3.

[0653] Example 191: Preparation of compound GT-10143

[0654] With reference to the method of Scheme 1, the target compound GT-10143 was obtained (12 mg, white solid, yield 33%). 1H NMR (400 MHz, DMSO-d6) 5 7.55 (d, J = 8.3 Hz, 1H), 7.24 - 7.16 (m, 5H), 6.76 (s, 1H), 5.12 (dd, J = 13.5, 5.1 Hz, 1H), 4.39 - 4.30 (m, 2H), 3.84 (dd, J = 11.3, 8.0 Hz, 2H), 3.77 (s, 2H), 3.65 (s, 1H), 3.45 - 3.37 (m, 1H), 3.06 (d, J = 9.1 Hz, 1H), 3.00 -2.88 (m, 4H), 2.84 - 2.75 (m, 1H), 2.62 - 2.57 (m, 4H), 2.46 (dd, J = 13.1, 4.8 Hz, 1H), 2.37 (brs, 3H), 2.29 (brs, 3H), 2.23 - 2.12 (m, 1H). LCMS (ESI) calcd. for C32H37FN5O3+ [M+H]+: 558.29, found, 558.3.

[0655] Example 192: Preparation of compound GT-10144

[0656] With reference to the method of Scheme 1, the target compound GT-10144 was obtained (14 mg, white solid, yield 37%). 1H NMR (400 MHz, DMSO-d6) 5 7.58 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 6.81 (s, 1H), 6.78 (d, J = 8.5 Hz, 1H), 5.11 (dd, J = 13.2, 5.1 Hz, 1H), 4.41 - 4.35 (m, 4H), 3.94 (t, J = 5.4 Hz, 2H), 3.91 - 3.84 (m, 3H), 3.36 (brs, 1H), 3.21 - 3.13 (m, 1H), 2.99 - 2.94 (m, 3H), 2.81 (brs, 1H), 2.78 - 2.69 (m, 1H), 2.68 - 2.58 (m, 3H), 2.54 - 2.43 (m, 4H), 2.19 - 2.13 (m, 1H). LCMS (ESI) calcd. for C31H35ClN5O4+ [M+H]+: 576.24, found, 576.3.

[0657] Example 193: Preparation of compound GT-10145

[0658] With reference to the method of Scheme 1, the target compound GT-10145 was obtained (11 mg, white solid, yield 30%). 1H NMR (400 MHz, DMSO-d6) 5 7.55 (d, J = 8.4 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), 6.79 (s, 1H), 6.76 (d, J = 8.5 Hz, 1H), 5.12 (dd, J = 13.2, 5.0 Hz, 1H), 4.39 - 4.33 (m, 4H), 3.94 (t, J = 5.4 Hz, 2H), 3.87 - 3.83 (m, 3H), 3.36 (d, J = 5.2 Hz, 1H), 3.14 (d, J = 9.5 Hz, 1H), 2.96 - 2.87 (m, 3H), 2.81 - 2.78 (m, 2H), 2.68 - 2.56 (m, 3H), 2.54 - 2.42 (m, 4H), 2.22 - 2.11 (m, 1H). LCMS (ESI) calcd. for C31H35FN5O4+ [M+H]+: 560.27, found, 560.3.

[0659] Example 194: Preparation of compound GT-10146

[0660] With reference to the method of Scheme 1, the target compound GT-10146 was obtained (20 mg, white solid, yield 50%). 1H NMR (400 MHz, DMSO-d6) 5 7.58 (d, J = 8.3 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.3 Hz, 2H), 6.78 (s, 1H), 6.76 (d, J = 8.4 Hz, 1H), 5.11 (dd, J = 13.2, 5.2 Hz, 1H), 4.42 - 4.32 (m, 4H), 3.89 (s, 2H), 3.83 (dd, J = 11.2, 7.6 Hz, 2H), 3.36 (brs, 1H), 3.06 (d, J = 8.8 Hz, 1H), 2.95 - 2.92 (m, 3H), 2.83 - 2.73 (m, 1H), 2.68 - 2.55 (m, 4H), 2.47 (dd, J = 13.2, 4.6 Hz, 1H), 2.39 - 2.36 (m, 2H), 2.20 - 2.15 (m, 1H), 1.32 (s, 6H). LCMS (ESI) calcd. for C33H39ClN5O4+ [M+H]+: 604.27, found, 604.3.

[0661] Example 195: Preparation of compound GT-10147

[0662] With reference to the method of Scheme 1, the target compound GT-10147 was obtained (16 mg, white solid, yield 40%). 1H NMR (400 MHz, DMSO-d6) 5 7.58 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.5 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 6.76 - 6.74 (m, 2H), 5.12 (dd, J = 13.2, 5.1 Hz, 1H), 4.38 (t, J = 10.0 Hz, 3H), 3.88 - 3.84 (m, 3H), 3.37 (d, J = 6.3 Hz, 1H), 3.04 (d, J = 8.5 Hz, 1H), 2.96 - 2.93 (m, 4H), 2.90 - 2.77 (m, 4H), 2.68 - 2.61 (m, 5H), 2.50 - 2.43 (m, 1H), 2.32 - 2.21 (m, 2H), 2.21 - 2.11 (m, 1H). LCMS (ESI) calcd. for C32H35ClFN5O3+ [M+H]+: 610.24, found, 610.3.

[0663] Example 196: Preparation of compound GT-10148

[0664] With reference to the method of Scheme 1, the target compound GT-10148 was obtained (13 mg, white solid, yield 32%). 1H NMR (400 MHz, DMSO-d6) 5 7.58 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 6.78 (s, 1H), 6.76 (d, J = 8.4 Hz, 1H), 5.12 (dd, J = 13.2, 5.1 Hz, 1H), 4.42 - 4.32 (m, 2H), 3.87 - 3.81 (m, 2H), 3.77 (s, 2H), 3.35 - 3.31 (m, 1H), 3.29 (s, 3H), 3.17 - 3.08 (m, 1H), 2.97 - 2.93 (m, 3H), 291 - 2.88 (m, 2H), 2.81 - 2.71 (m, 3H), 2.66 - 2.54 (m, 3H), 2.50 - 2.45 (m, 1H), 2.35 - 2.31 (m, 2H), 2.22 - 2.13 (m, 1H), 2.05 - 2.00 (m, 1H), 1.80 - 1.71 (m, 1H), 1.34 (s, 3H). LCMS (ESI) calcd. for C34H41ClN5O4+ [M+H]+: 618.28, found, 618.3.

[0665] Example 197: Preparation of compound GT-10149

[0666] With reference to the method of Scheme 1, the target compound GT-10149 was obtained (7 mg, white solid, yield 19%). 1H NMR (400 MHz, DMSO-d6) 5 7.54 (d, J = 8.3 Hz, 1H), 7.24 - 7.13 (m, 5H), 6.77 - 6.74 (m, 1H), 5.12 (dd, J = 13.4, 5.2 Hz, 1H), 4.35 - 4.32 (m, 2H), 3.86 -3.76 (m, 3H), 3.26 (dd, J = 11.8, 6.4 Hz, 1H), 3.02 - 2.97 (m, 4H), 2.85 - 2.77 (m, 1H), 2.63 - 2.55 (m, 4H), 2.49 - 2.41 (m, 1H), 2.33 (brs, 3H), 2.19 - 2.12 (m, 3H), 1.64 - 1.58 (m, 2H), 1.05 (s, 6H). LCMS (ESI) calcd. for C34H41FN5O3+ [M+H]+: 586.32, found, 586.4.

[0667] Example 198: Preparation of compound GT-10232

[0668] With reference to the method of Scheme 1, the target compound GT-10232 was obtained (28 mg, white solid, yield 74%). 1H NMR (400 MHz, MeOD) 5 7.88 - 7.79 (m, 1H), 7.63 - 7.51 (m, 5H), 7.47 - 7.38 (m, 3H), 6.94 (s, 1H), 6.88 (d, J = 8.4 Hz, 1H), 5.07 (dd, J = 13.6, 5.0 Hz, 1H), 4.42 - 4.28 (m, 4H), 3.82 (s, 2H), 3.05 (d, J = 12.8 Hz, 2H), 2.95 (d, J = 12.5 Hz, 2H), 2.86 (dd, J = 13.2, 5.1 Hz, 1H), 2.80 - 2.69 (m, 1H), 2.43 (dd, J = 13.1, 5.0 Hz, 1H), 2.22 - 2.06 (m, 3H), 1.57 - 1.44 (m, 2H). LCMS (ESI) calcd. for C32H33ClN5O3+ [M+H]+: 570.23, found, 570.3.

[0669] Example 199: Preparation of compound GT-10233

[0670] With reference to the method of Scheme 1, the target compound GT-10233 was obtained (27 mg, white solid, yield 72%). 1H NMR (400 MHz, MeOD) 5 7.90 (s, 1H), 7.78 (s, 1H), 7.72 -7.64 (m, 2H), 7.61 - 7.56 (m, 3H), 7.48 (dd, J = 8.5, 1.6 Hz, 2H), 7.02 (s, 1H), 6.95 (d, J = 8.1 Hz, 1H), 5.08 (dd, J = 13.1, 3.7 Hz, 1H), 4.44 - 4.26 (m, 4H), 4.04 (s, 2H), 3.16 (d, J = 11.6 Hz, 2H), 3.06 (d, J = 11.9 Hz, 2H), 2.97 - 2.81 (m, 1H), 2.76 (d, J = 17.7 Hz, 1H), 2.56 - 2.33 (m, 5H), 2.19 - 2.05 (m, 1H). LCMS (ESI) calcd. for C32H33ClN5O3+ [M+H]+: 570.23, found, 570.3.

[0671] Example 200: Preparation of compound GT-10234

[0672] With reference to the method of Scheme 1, the target compound GT-10234 was obtained (12 mg, white solid, yield 32%). 1H NMR (400 MHz, MeOD) 5 7.55 (d, J = 8.4 Hz, 1H), 7.28 -7.20 (m, 2H), 7.15 (t, J = 8.6 Hz, 2H), 6.96 (s, 1H), 6.90 (d, J = 8.4 Hz, 1H), 5.07 (dd, J = 13.5, 5.2 Hz, 1H), 4.43 - 4.26 (m, 2H), 3.89 (s, 2H), 3.64 (s, 2H), 3.11 - 2.98 (m, 4H), 2.91 - 2.81 (m, 1H), 2.77 - 2.67 (m, 1H), 2.45 - 2.35 (m, 3H), 2.31 (s, 2H), 2.23 - 2.07 (m, 3H), 1.82 (s, 4H), 1.54 - 1.40 (m, 2H). LCMS (ESI) calcd. for C32H37FN5O3+ [M+H]+: 558.29, found, 558.3.

[0673] Example 201: Preparation of compound GT-10235

[0674] With reference to the method of Scheme 1, the target compound GT-10235 was obtained (13 mg, white solid, yield 34%). 1H NMR (400 MHz, MeOD) 5 7.58 (d, J = 8.3 Hz, 1H), 7.52 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 7.00 (s, 1H), 6.94 (d, J = 8.1 Hz, 1H), 5.10 (dd, J = 13.3, 5.1 Hz, 1H), 4.48 - 4.27 (m, 5H), 3.97 - 3.92 (m, 3H), 3.71 (s, 2H), 3.15 - 3.05 (m, 4H), 2.97 -2.85 (m, 1H), 2.76 (d, J = 15.7 Hz, 1H), 2.53 (s, 2H), 2.45 (dd, J = 13.2, 4.5 Hz, 1H), 2.21 - 2.06 (m, 3H), 1.46 - 1.44 (m, 2H). LCMS (ESI) calcd. for C31H35ClN5O4+ [M+H]+: 576.24, found, 576.3.

[0675] Example 202: Preparation of compound GT-10236

[0676] With reference to the method of Scheme 1, the target compound GT-10236 was obtained (12 mg, white solid, yield 32%).1H NMR (400 MHz, MeOD) 5 7.54 (d, J = 8.3 Hz, 1H), 7.35 -7.28 (m, 2H), 7.22 - 7.17 (m, 2H), 6.95 (s, 1H), 6.89 (d, J = 8.4 Hz, 1H), 5.06 (dd, J = 13.3, 5.1 Hz, 1H), 4.38 (s, 2H), 4.33 (d, J = 7.7 Hz, 2H), 3.97 - 3.89 (m, 3H), 3.72 (s, 2H), 3.19 - 3.09 (m, 1H), 3.07 (s, 3H), 2.91 - 2.81 (m, 1H), 2.75 (d, J = 17.7 Hz, 1H), 2.51 (s, 2H), 2.46 - 2.37 (m, 1H), 2.33 - 2.30 (m, 1H), 2.18 - 2.05 (m, 3H), 1.45 - 1.42 (m, 2H). LCMS (ESI) calcd. for C31H35FN5O4+ [M+H]+: 560.27, found, 560.3.

[0677] Example 203: Preparation of compound GT-10237

[0678] With reference to the method of Scheme 1, the target compound GT-10237 was obtained (12 mg, white solid, yield 30%). 1H NMR (400 MHz, MeOD) 5 7.55 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 6.95 (s, 1H), 6.89 (d, J = 8.4 Hz, 1H), 5.07 (dd, J = 13.3, 5.1 Hz, 1H), 4.40 (s, 2H), 4.34 (d, J = 7.2 Hz, 2H), 3.89 (s, 2H), 3.73 (s, 2H), 3.14 - 2.97 (m, 4H), 2.92 - 2.81...

Claims

1. A compound of Formula (I)o 0 (Ras)m         (Rd2)n2 (Rds)n3(I)or salts, enantiomers, stereoisomers, isotopically enriched analogs, solvates, or polymorphs thereof as claimed in claim,wherein Z represents C(O), CH2, or CD2;Ra1, Ra2, Ra3, and Ra4 each independently represent hydrogen, deuterium, halogen, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, or halogenated C1-6 alkoxy;(Ra5)m indicates that the isoindoline ring to which it is attached is optionally substituted with m Ra5, wherein each Ra5 is identical or different and independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl;m represents an integer of 0, 1, 2, or 3;R represents:(Rd1 )n1wherein ring A1 represents heterocyclylene containing at least two nitrogen atoms, and (Rd1)n1 indicates that ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20; andR1 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl, and R2 represents a bond, CH2, or C(O); orR1 represents a bond, and R2 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl, or R2 represents N(Rw)C(O) *, where Rw represents hydrogen or C1-3 alkyl, or R2 represents -N=CH-*; orR represents:wherein RX represents NH, -N=CH-*, or N(Rw)C(O) *, wherein Rw represents hydrogen orC1-3 alkyl; orR represents:(Rd4)n4wherein ring A2 represents heterocyclylene containing one nitrogen atom, and (Rd4)n4 indicates that ring A2 is optionally substituted with n4 Rd4 groups, wherein each Rd4 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n4 represents an integer of 0-20; andwherein Ryi represents       0-2  , symbol ** indicates the point of attachment to ring A2;and Ry2 represents N(Rw) or N(Rw)C(O) *, where Rw represents hydrogen or C1-3 alkyl; and the symbol * in each of the above formulae indicates the point of attachment to Rc; and Rc represents CRc1Rc2, where Rc1 and Rc2 each independently represent H, deuterium, halogen, optionally substituted linear or branched alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or Rc represents a bond;ring B represents cycloalkylene, heterocyclylene, arylene, or heteroarylene, m1 represents an integer of 0 or 1, and (Rd2)n2 indicates that ring B is optionally substituted with n2 Rd2 groups, wherein each Rd2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and n2 represents an integer of 0-20; andring C represents heterocyclyl, cycloalkyl, aryl, or heteroaryl, and (Rd3)n3 indicates that ring C is optionally substituted with n3 Rd3 groups, wherein each Rd3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and n3 represents an integer of 0-20;with the proviso that the following compounds are excluded:3-(5-((4-benzhydrylpiperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

2. The compound of Formula (I) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in claim 1, wherein(i) Ra1, Ra2, Ra3, and Ra4 each independently represent H; and / or(ii) ring A1 represents 4- to 20-membered heterocyclylene containing at least two nitrogen atoms (including 4- to 20-membered heterocyclene and 4- to 15-membered heterocyclene), and (Rd1)n1 indicates that ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20; and / or(iii) R1 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl, and R2 represents a bond; or(iv) R1 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl, and R2 represents CH2 or C(O); or(v) R1 represents a bond, and R2 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl; or(vi) R1 represents a bond, and R2 represents N(Rw)C(O) *, where Rw represents hydrogen or C1-3 alkyl; or(vii) R1 represents a bond, and R2 represents -N=CH-*; and / or(viii) ring A2 represents 4- to 30-membered heterocyclylene containing one nitrogen atom (including 4- to 20-membered heterocyclylene and 4- to 15-membered heterocyclylene), and (Rd4)n4 indicates that ring A2 is optionally substituted with n4 Rd4 groups, wherein each Rd4 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n4 represents an integer of 0-20; and / or(iv) Rc represents CRc1Rc2, where Rc1 and Rc2 each independently represent H, deuterium, halogen, optionally substituted linear or branched C1-10 alkyl, optionally substituted C3-30 cycloalkyl, optionally substituted C5-30 aryl, optionally substituted 4- to 30-membered heterocyclyl, or optionally substituted 5- to 30-membered heteroaryl, or Rc represents abond; and / or(v) ring B represents 4- to 30-membered heterocyclylene, C3-30 cycloalkylene, C5-30 arylene, or 5- to 30-membered heteroarylene, m1 represents an integer of 0 or 1, and (Rd2)n2 indicates that ring B is optionally substituted with n2 Rd2 groups, wherein each Rd2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and n2 represents an integer of 0-20; and / or(vi) ring C represents C3-30 cycloalkyl, 4- to 30-membered heterocyclyl, C5-30 aryl, or 5- to 30membered heteroaryl, and (Rd3)n3 indicates that ring C is optionally substituted with n3 Rd3 groups, wherein each Rd3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and n3 represents an integer of 0-20.

3. The compound of Formula (I) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in claim 1, wherein R represents one of the following formulae:wherein each Rw independently represents hydrogen or C1-3 alkyl;each ring A1 independently represents heterocyclylene containing at least two nitrogen atoms, and (Rd1)n1 indicates that ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20;ring A2 represents heterocyclylene containing one nitrogen atom, and (Rd4)n4 indicates that ring A2 is optionally substituted with n4 Rd4 groups, wherein each Rd4 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n4 represents an integer of 0-20; andsymbol * indicates the point of attachment to Rc .

4. The compound of Formula (I) or salts, enantiomers, stereoisomers, solvates, or polymorphsthereof as claimed in any one of claims 1-3, wherein(i) each ring A1 independently represents 4- to 20-membered heterocyclylene containing at least two nitrogen atoms (including 4- to 15-membered heterocyclylene), and (Rd1)n1 indicates that ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 020; or(ii) ring A2 represents 4- to 20-membered heterocyclylene containing one nitrogen atom (including 4- to 15-membered heterocyclylene), and (Rd4)n4 indicates that ring A2 is optionally substituted with n4 Rd4 groups, wherein each Rd4 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n4 represents an integer of 0-20; and / or(iii) the Rc1 and Rc2 each independently represent H, deuterium, halogen, optionally substituted linear or branched C1-6 alkyl, optionally substituted C3-20 cycloalkyl (including optionally substituted C3-15 cycloalkyl), optionally substituted C5-20 aryl (including optionally substituted C5-15 aryl), optionally substituted 4- to 20-membered heterocyclyl (including optionally substituted 4- to 15-membered heterocyclyl), or optionally substituted 5- to 20-membered heteroaryl (including optionally substituted 5- to 15-membered heteroaryl); and / or(iv) ring B represents 4- to 20-membered heterocyclylene (including 4- to 15-membered heterocyclylene), C3-20 cycloalkylene (including C3-15 cycloalkylene), C5-20 arylene (including C5-15 arylene), or 5- to 20-membered heteroarylene (including 5- to 15-membered heteroarylene), m1 represents an integer of 0 or 1, and (Rd2)n2 indicates that ring B is optionally substituted with n2 Rd2 groups, wherein each Rd2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and n2 represents an integer of 0-20; and / or(v) ring C represents C3-20 cycloalkyl (including C3-15 cycloalkyl), 4- to 20-membered heterocyclyl (including 4- to 15-membered heterocyclyl), C5-20 aryl (including C5-15 aryl), or 5- to 20-membered heteroaryl (including 5- to 15-membered heteroaryl), and (Rd3)n3 indicates that ring C is optionally substituted with n3 Rd3 groups, wherein each Rd3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and n3 represents an integer of 0-20.

5. The compound of Formula (I) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in claim 1, wherein(i) Z represents C(O) or CH2; and / or(ii) each ring A1 independently represents 1,3-diazetidinylidene, imidazolidylene, pyrazolidylene,       piperazinylene,       diazacycloheptanylene,       diazacyclooctylene,diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene, diazabicyclo[2.2.2]octanylene, 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonanylene, 2,8-diazaspiro[4.5]decanylene, 3,9-diazaspiro[5.5]undecanylene, or octahydropyrrolo[3,4-c]pyrrolylene, each optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20 (e.g., an integer of 0-10); or(iii) ring    A2    represents azetidinylene, pyrrolidinylene, piperidinylene,dihydroxypiperidinylene,     difluoropiperidinylene,     azepanylene,     azacyclooctylene,monoazabridged-cycloalkylene (e.g., 6- to 20-membered monoazabridged-cycloalkylene, such as 6-azabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, and quinuclidinylene), or monoazaspirocycloalkylene (e.g., 5- to 20-membered monoazaspirocycloalkylene, such as 3-azaspiro[5.5]undecanylene and 7-azaspiro[3.5]nonanylene), each optionally substituted with n4 Rd4 groups, wherein each Rd4 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n4 represents an integer of 0-20 (e.g., an integer of 0-10); and / or(iv) Rc1 and Rc2 each independently represent:H, deuterium, halogen, or optionally substituted linear or branched C1-10 alkyl; or cyclopropyl,  cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl,cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C5-C20 spiro-cycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, and spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C20 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl), each optionally substituted with one or more (e.g., 1-10) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, and C2-6 alkynyl; orazetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl,piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxy-piperidinyl, difluoro-piperidinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, dioxacyclohexyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl, 4,5-diazacycloheptanyl, 1,3-diazacycloheptanyl), diazacyclooctyl, bridged heterocyclyl (e.g., 6-to 20-membered bridged heterocyclyl, such as 6-azabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl,            3,8-diazabicyclo[3.2.1]octanyl,            2,5-diazabicyclo[2.2.2]octanyl, and quinuclidinyl), and azaspirocycloalkyl (e.g., 5- to 20membered azaspirocycloalkyl, such as 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl, and 7-azaspiro[3.5]nonanyl), or octahydropyrrolo[3,4-c]pyrrolyl, each optionally substituted with one or more (e.g., 1-10) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, amino, cyano, oxo, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, and C2-6 alkynyl; orphenyl or naphthyl, each optionally substituted with one or more (e.g., 1-7) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, and C2-6 alkynyl; orfuranyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl,      quinolinyl,      isoquinolinyl,       1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl,       5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl,thieno[2,3-d]pyrimidinyl,       thieno[3,2-d]pyrimidinyl,       isoxazolo[4,5-c]pyridinyl,isoxazolo[4,5-c]pyrimidinyl,    isoxazolo[4,5-d]pyrimidinyl,    pyrazolo[1,5-a]pyridinyl,pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl,            or            6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each optionally substituted with one or more (e.g., 1-10) substituents independently selected from the group consisting of deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, and C2-6 alkynyl; and / or(v) ring B represents:cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, spiro-cycloalkylene (e.g., C5-C20 spiro-cycloalkylene, such as spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[3.5]nonenylene, spiro[4.4]nonylene, spiro[4.5]decylene, spiro[4.5]decenylene, and spiro[5.5]undecylene), p-menthanylene, m-menthanylene, or bridged cycloalkylene (e.g., C6-C20 bridged cycloalkylene, such as adamantanylene, noradamantanylene, bornylene, norbornylene,      bicyclo[2.2.1]heptylene,      2-oxobicyclo[2.2.1]heptylene,      orbicyclo[2.2.1]heptentylene), each optionally substituted with 0-20 (e.g., 0-10) substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, and C2-6 alkenyl; orazetidinylene, oxetanylene, pyrrolidinylene, imidazolidylene, pyrazolidylene, oxetanylene,     dihydropyranylene,     tetrahydropyranylene,     tetrahydrothienylene,tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, tetrahydropyridinylene, dihydroxypiperidinylene, difluoropiperidinylene, morpholinylene, thiomorpholinylene,      dioxacyclohexylene,      azepanylene,      azacyclooctylene,diazacycloheptanylene (e.g., 1,4-diazacycloheptanylene, 4,5-diazacycloheptanylene, 1,3-diazacycloheptanylene), diazacyclooctylene, bridged heterocyclylene (e.g., 6- to 20membered bridged heterocyclylene, such as 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene,           3,6-diazabicyclo[3.1.1]heptanylene,           3-azabicyclo[3.2.1]octanylene,            3,8-diazabicyclo[3.2.1]octanylene,            2,5-diazabicyclo[2.2.2]octanylene, and quinuclidinylene), azaspirocycloalkylene (e.g., 5- to 20membered azaspirocycloalkylene, such as 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonanylene, 2,8-diazaspiro[4.5]decanylene, 3,9-diazaspiro[5.5]undecanylene, 3-azaspiro[5.5]undecanylene, and 7-azaspiro[3.5]nonanylene), or octahydropyrrolo[3,4-c]pyrrolylene, each optionally substituted with 0-20 (e.g., 0-10) substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl,halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, and C2-6 alkenyl; orphenylene or naphthylene, each optionally substituted with 0-20 (e.g., 0-6) substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, C2-6 alkynyl, and C2-6 alkenyl; orfuranylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, triazinylene, indolylene, isoindolylene, indolinylene, benzofuranylene, chromanylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene,     benzo[1,2,3]thiadiazolylene,     2-oxo-2,3-dihydro-1H-benzo[d]imidazolylene,            benzo[b][1,4]oxazinylene,            3,4-dihydro-2H-benzo[b][1,4]oxazinylene, quinolinylene, isoquinolinylene, 1,2,3,4-tetrahydroquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, 1,2,3,4-tetrahydroquinoxalinylene,     phthalazinylene,     5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinylene, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinylene, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinylene, thieno[2,3-d]pyrimidinylene, thieno[3,2-d]pyrimidinylene, isoxazolo[4,5-c]pyridinylene,     isoxazolo[4,5-c]pyrimidinylene,     isoxazolo[4,5-d]pyrimidinylene,pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene, imidazo[2,1-b]thiazolylene, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinylene, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinylene, each optionally substituted with 0-20 (e.g., 0-10) substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, C2-6 alkynyl, and C2-6 alkenyl; and / or(vi) ring C represents:cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C5-C20 spiro-cycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, and spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C20 bridgedcycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl), each optionally substituted with 0-20 (e.g., 1-10) substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, and C2-6 alkenyl; orazetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxy-piperidinyl, difluoro-piperidinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl,   dioxacyclohexyl,azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl, 4,5-diazacycloheptanyl, 1,3-diazacycloheptanyl), diazacyclooctyl, bridged heterocyclyl (e.g., 6-to 20-membered bridged heterocyclyl, such as 6-azabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5- diazabicyclo[2.2.2]octanyl, and quinuclidinyl), and azaspirocycloalkyl (e.g.,  5- to 20-membered azaspirocycloalkyl, such as 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl, and 7-azaspiro[3.5]nonanyl), or octahydropyrrolo[3,4-c]pyrrolyl, each optionally substituted with 0-20  (e.g.,  1-10)substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, and C2-6 alkenyl; orphenyl or naphthyl, each optionally substituted with 0-20 (e.g., 0-6) substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, C2-6 alkynyl, and C2-6 alkenyl; orfuranyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl,      quinolinyl,      isoquinolinyl,       1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl,4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl,       5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl,thieno[2,3-d]pyrimidinyl,       thieno[3,2-d]pyrimidinyl,       isoxazolo[4,5-c]pyridinyl,isoxazolo[4,5-c]pyrimidinyl,    isoxazolo[4,5-d]pyrimidinyl,    pyrazolo[1,5-a]pyridinyl,pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl,            or            6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each optionally substituted with 0-20 (e.g., 1-10) substituents independently selected from the group consisting of deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, C2-6 alkynyl, and C2-6 alkenyl.

6. The compound of Formula (I) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in claim 1, wherein(i) R represents one of the following structures:wherein symbol * indicates the point of attachment to Rc ; and / or(ii) the       (Rd2)n2 (Rd3)n3 moiety of the compound of Formula (I) represents one of the followingstructures:thereof as claimed in claim 1, which is selected from the compounds in Table 1.

8. The compound of Formula (I) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in any one of claims 1-7, which is hydrohalides (including hydrochlorides, hydrobromides), sulfates, citrates, maleates, lactates, lactobionates, L-tartrates, fumarates, L-malates, L-lactates, a-Ketoglutarates, hippurates, D-glucuronates, D-gluconates, a-D-glucoheptonates, glycolates, mucates, L-ascorbates, orotates, picrates, glycinates, alaninates, argininates, cinnamates, laurates, pamoates, sebacates, benzenesulfonates, methanesulfonates, ethanesulfonates, edisylates, formates, acetates, 2,2-dichloroacetates, trimethylacetates, propionates, valerates, palmitates, triphenylacetates, 2-ethylsuccinates, iodates, niacinates, L-pyroglutamates, L-prolinates, ferulates, 2-hydroxyethanesulfonates, nitrates, gentisates, cholates, salicylates, terephthalates, glutarates, adipates, stearates, oleates, undecenoates, camphorates, camphorsulfonates, dodecyl sulfonates, phosphates, thiocyanates, dihydrophosphates, pyrophosphates, metaphosphates, oxalates, carbonates, malonates, benzoates, mandelates, succinates, pyruvates, para-chlorobenzenesulfonates, 1,5-naphthalenedisulfonates, 3-hydroxy-2-naphthoates, 1-hydroxy-2-naphthoates, 2-naphthalenesulfonates, trifluoroacetate, glycolate, or 4-methylbenzenesulfonate of the compound of Formula (I) or (I’).

9. A compound of Formula (I’)(I’)or salts, enantiomers, stereoisomers, isotopically enriched analogs, solvates, or polymorphs thereof, wherein Z represents C(O), CH2, or CD2;Ra1, Ra2, Ra3, and Ra4 each independently represent hydrogen, deuterium, halogen, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, or halogenated C1-6 alkoxy;(Ra5)m indicates that the isoindoline ring to which it is attached is optionally substituted with m Ra5, wherein each Ra5 is identical or different and independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or heterocyclyl, wherein said heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-6 alkyl, and tert-butoxycarbonyl;m represents an integer of 0, 1, 2, or 3;ring A1 represents heterocyclylene containing at least two nitrogen atoms, and (Rd1)n1 indicates that ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20; andR1 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl optionally substituted with one or more substituents independently selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl, and R2 represents a bond; orR1 represents a bond, and R2 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl; andRe represents a bond or C(O)O, or Re represents the structure of the following formula:(Re2)m2 (Re3)m3Re1 represents C(O), CH2 or halogenated CH2;ring D represents arylene, and (Re2)m2 indicates that the ring D is optionally substituted with m2 Re2 groups, wherein each Re2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m2 represents an integer of 0-20; andring E represents nitrogen-containing heterocyclylene, m4 represents an integer of 0 or 1, and (Re3)m3 indicates that the ring E is optionally substituted with m3 Re3 groups, wherein each Re3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m3 represents an integer of 020;symbol # indicates the point of attachment to Rf ;Rf represents C1-10 alkyl, wherein said C1-10 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of: halogen, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, and NR3R4, where R3 and R4 each independently represent H, C1-3 alkyl, or optionally substituted cycloalkyl;with the proviso that the following compounds are excluded:3-(5-((4-benzhydrylpiperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

10. The compound of Formula (I’) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in claim 9, wherein(i) Ra1, Ra2, Ra3, and Ra4 each independently represent H; and / or(ii) ring A1 represents 4- to 20-membered heterocyclylene containing at least two nitrogen atoms, and (Rd1)n1 indicates that ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20; and / or(iii) R1 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl optionally substituted with one or more substituents independently selected from the group consisting of optionally substituted C5-30 aryl and optionally substituted 5- to 30-membered heteroaryl, and R2 represents a bond; or(iv) R1 represents a bond, and R2 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl; and / or(v) Re represents a bond or C(O)O; or(vi) ring D represents C5-30 arylene, and (Re2)m2 indicates that the ring D is optionally substituted with m2 Re2 groups, wherein each Re2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m2 represents an integer of 0-20; and / or(vii) ring E represents 4- to 30-membered nitrogen-containing heterocyclylene, m4 represents an integer of 0 or 1, and (Re3)m3 indicates that the ring E is optionally substituted with m3 Re3 groups, wherein each Re3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m3 represents an integer of 0-20; and / or(viii) Rf represents C1-10 alkyl, wherein said C1-10 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of: halogen, optionally substituted C5-30 aryl, optionally substituted 5- to 30-membered heteroaryl, optionally substituted 4- to 30-membered heterocyclyl, optionally substituted C3-30 cycloalkyl, and NR3R4, where R3 and R4 each independently represent H, C1-3 alkyl, oroptionally substituted C3-30 cycloalkyl; and / or(ix) Ra5 represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 4- to 20-membered heterocyclyl, wherein said 4- to 20-membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-6 alkyl, and tert-butoxycarbonyl;wherein said C5-30 aryl and 5- to 30-membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl; and said 4- to 30-membered heterocyclyl and C3-30 cycloalkyl are each independently optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tertbutoxycarbonyl, and optionally substituted C5-15 aryl, wherein said C5-15 aryl is optionally substituted with one or more substituents selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy.

11. The compound of Formula (I’) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in claim 9 or 10, wherein(i) ring A1 represents 4- to 15-membered heterocyclylene containing at least two nitrogen atoms, and (Rd1)n1 indicates that ring A1 is optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20; and / or(ii) R1 represents N(Rw), where Rw represents hydrogen or C1-3 alkyl optionally substituted with one or more substituents selected from the group consisting of optionally substituted C5-20 aryl (including optionally substituted C5-15 aryl) and optionally substituted 5- to 20-membered heteroaryl (including optionally substituted 5- to 15membered heteroaryl), and R2 represents a bond; or(iii) ring D represents C5-20 arylene (including C5-15 arylene), and (Re2)m2 indicates that the ring D is optionally substituted with m2 Re2 groups, wherein each Re2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6alkynyl, or C2-6 alkenyl, and m2 represents an integer of 0-20; and / or(iv) ring E represents 4- to 20-membered nitrogen-containing heterocyclylene (including 4- to 15-membered nitrogen-containing heterocyclylene), m4 represents an integer of 0 or 1, and (Re3)m3 indicates that the ring E is optionally substituted with m3 Re3 groups, wherein each Re3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m3 represents an integer of 020; and / or(v) Rf represents C1-10 alkyl, wherein said C1-10 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of: halogen, optionally substituted C5-20 aryl (including optionally substituted C5-15 aryl), optionally substituted 5- to 20-membered heteroaryl (including optionally substituted 5- to 15-membered heteroaryl), optionally substituted 4- to 20-membered heterocyclyl (including optionally substituted 4- to 15-membered heterocyclyl), optionally substituted C3-20 cycloalkyl (including optionally substituted C3-15 cycloalkyl), and NR3R4, where R3 and R4 each independently represent H, C1-3 alkyl, or optionally substituted C3-20 cycloalkyl (including optionally substituted C3-15 cycloalkyl); and / or(vi) Ra5 represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, deuterated C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 4- to 15-membered heterocyclyl, wherein said 4- to 15-membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-6 alkyl, and tert-butoxycarbonyl;wherein said C5-20 aryl and 5- to 20-membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl; and said 4- to 20-membered heterocyclyl and C3-20 cycloalkyl are each independently optionally substituted with one or more substituents selected from the group consisting of: halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tertbutoxycarbonyl, and C5-15 aryl optionally substituted with one or more substituents selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy.thereof as claimed in any one of claims 9-11, wherein(i) ring A1 represents 1,3-diazetidinylidene, imidazolidylene, pyrazolidylene, piperazinylene, diazacycloheptanylene,        diazacyclooctylene,        diazabicyclo[3.1.1]heptanylene,diazabicyclo[2.2.1]heptanylene,                             diazabicyclo[3.2.1]octanylene,diazabicyclo[2.2.2]octanylene,             2,6-diazaspiro[3.3]heptanylene,             2,7-diazaspiro[3.5]nonanylene, 2,8-diazaspiro[4.5]decanylene, 3,9-diazaspiro[5.5]undecanylene, or octahydropyrrolo[3,4-c]pyrrolylene, each optionally substituted with n1 Rd1 groups, wherein each Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, or C1-6 alkoxy, and n1 represents an integer of 0-20 (e.g., an integer of 0-10); and / or(ii) Rw represents hydrogen or C1-3 alkyl, wherein the C1-3 alkyl is optionally substituted with one or more substituents selected from the group consisting of:phenyl or naphthyl, each optionally substituted with one or more (e.g., 1-7) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl; andfuranyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl,                  2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl,benzo[b][1,4]oxazinyl,      3,4-dihydro-2H-benzo[b][1,4]oxazinyl,      quinolinyl,isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl,      1H-pyrrolo[2,3-b]pyridinyl,     pyrrolo[2,1-b]thiazolyl,imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each optionally substituted with one or more (e.g., 1-10) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl,halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl; and / or(iii) ring D represents phenylene or naphthylene, each optionally substituted with m2 Re2 groups, wherein each Re2 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m2 represents an integer of 0-20 (e.g., an integer of 0-10); and / or(iv) ring E represents azetidinylene, pyrrolidinylene, imidazolidylene, pyrazolidylene, piperidinylene, piperazinylene, tetrahydropyridinylene, dihydroxypiperidinylene, difluoropiperidinylene, azepanylene, azacyclooctylene, diazacycloheptanylene (e.g., 1,4-diazacycloheptanylene, 4,5-diazacycloheptanylene, 1,3-diazacycloheptanylene), diazacyclooctylene, nitrogen-containing bridged heterocyclylene (e.g., 6- to 20-membered nitrogen-containing bridged heterocyclylene, such as 6-azabicyclo[3.1.1]heptanylene,        2,5-diazabicyclo[2.2.1]heptanylene,        3,6-diazabicyclo[3.1.1]heptanylene,          3-azabicyclo[3.2.1]octanylene,          3,8-diazabicyclo[3.2.1]octanylene,         2,5-diazabicyclo[2.2.2]octanylene,         andquinuclidinylene), azaspirocycloalkylene (e.g.,    5- to 20-memberedazaspirocycloalkylene,     such     as     2,6-diazaspiro[3.3]heptanylene,     2,7-diazaspiro[3.5]nonanylene,            2,8-diazaspiro[4.5]decanylene,            3,9-diazaspiro[5.5]undecanylene,       3-azaspiro[5.5]undecanylene,       and       7-azaspiro[3.5]nonanylene), or octahydropyrrolo[3,4-c]pyrrolylene, each optionally substituted with m3 Re3 groups, wherein each Re3 independently represents deuterium, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C2-6 alkynyl, or C2-6 alkenyl, and m3 represents an integer of 0-20 (e.g., an integer of 0-10), and m4 represents an integer of 0 or 1; and / or(v) Rf represents C1-10 alkyl, wherein said C1-10 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of:halogen;phenyl or naphthyl, each optionally substituted with one or more (e.g., 1-7) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl;furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl,pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl,                  2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl,benzo[b][1,4]oxazinyl,      3,4-dihydro-2H-benzo[b][1,4]oxazinyl,      quinolinyl,isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl,      1H-pyrrolo[2,3-b]pyridinyl,     pyrrolo[2,1-b]thiazolyl,imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each optionally substituted with one or more (e.g., 1-10) substituents independently selected from the group consisting of halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, and C2-6 alkenyl;azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxy-piperidinyl, difluoro-piperidinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, dioxacyclohexyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g.,  1,4-diazacycloheptanyl, 4,5-diazacycloheptanyl, 1,3-diazacycloheptanyl), diazacyclooctyl, bridged heterocyclyl (e.g., 6- to 20-membered bridged heterocyclyl, such as 6-azabicyclo[3.1.1]heptanyl,            2,5-diazabicyclo[2.2.1]heptanyl,            3,6-diazabicyclo[3.1.1]heptanyl,             3-azabicyclo[3.2.1]octanyl,             3,8-diazabicyclo[3.2.1]octanyl,            3,8-diazabicyclo[3.2.1]octanyl,            2,5-diazabicyclo[2.2.2]octanyl, and quinuclidinyl), and azaspirocycloalkyl (e.g., 5- to 20membered azaspirocycloalkyl, such as 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl, and 7-azaspiro[3.5]nonanyl), or octahydropyrrolo[3,4-c]pyrrolyl, each optionally substituted with one or more (e.g., 1-10) substituentsindependently selected from the group consisting of: halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tert-butoxycarbonyl, and C5-15 aryl optionally substituted with one or more (e.g., 1-5) substituents selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy;cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spiro-cycloalkyl (e.g., C5-C20 spiro-cycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, and spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C20 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl), each optionally substituted with one or more (e.g., 1-10) substituents independently selected from the group consisting of: halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tert-butoxycarbonyl, and C5-15 aryl optionally substituted with one or more (e.g., 1-5) substituents selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy; andNR3R4, where R3 and R4 each independently represent:H;C1-3 alkyl; orcyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spiro-cycloalkyl (e.g., C5-C20 spiro-cycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, and spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C20 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl), each optionally substituted with one or more (e.g., 1-10) substituents independently selected from the group consisting of: halogen, amino, hydroxyl, mercapto, cyano, oxo, C1-6 alkyl, deuterated C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, tert-butoxycarbonyl, and C5-15 aryl optionally substituted with one or more (e.g., 1-5) substituents selected from the group consisting of halogen, C1-6 alkyl, and C1-6 alkoxy.

13. The compound of Formula (I’) or salts, enantiomers, stereoisomers, solvates, or polymorphsthereof as claimed in any one of claims 9-12, whereinfyyy(i) Rw represents H or        ■ ; / -h(ii) Re represents a bond, C(O)O,            , or o   '—'   '—'    , where symbol # indicatesthe point of attachment to Rf ;(iii) Rf represents:”T                         H r^\    / -0   / —\ / =\methyl, isopropyl, tert-butyl,      ^, kk,                       ,          >*        ,>CM>ci or '               .

14. The compound of Formula (I’) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in claim 9, which is selected from the compounds in Table 2.

15. The compound of Formula (I’) or salts, enantiomers, stereoisomers, solvates, or polymorphs thereof as claimed in any one of claims 9-14, which is hydrohalides (including hydrochlorides, hydrobromides), sulfates, citrates, maleates, lactates, lactobionates, L-tartrates, fumarates, L-malates, L-lactates, a-Ketoglutarates, hippurates, D-glucuronates, D-gluconates, a-D-glucoheptonates, glycolates, mucates, L-ascorbates, orotates, picrates, glycinates, alaninates, argininates, cinnamates, laurates, pamoates, sebacates, benzenesulfonates, methanesulfonates, ethanesulfonates, edisylates, formates, acetates, 2,2-dichloroacetates, trimethylacetates, propionates, valerates, palmitates, triphenylacetates, 2-ethylsuccinates, iodates, niacinates, L-pyroglutamates, L-prolinates, ferulates, 2-hydroxyethanesulfonates, nitrates, gentisates, cholates, salicylates, terephthalates, glutarates, adipates, stearates, oleates, undecenoates, camphorates, camphorsulfonates, dodecyl sulfonates, phosphates, thiocyanates, dihydrophosphates, pyrophosphates, metaphosphates, oxalates, carbonates, malonates, benzoates, mandelates, succinates, pyruvates, para-chlorobenzenesulfonates, 1,5-naphthalenedisulfonates, 3-hydroxy-2-naphthoates, 1-hydroxy-2-naphthoates, 2-naphthalenesulfonates, trifluoroacetate, glycolate, or 4-methylbenzenesulfonate of the compound of Formula (I) or Formula (I’).

16. A pharmaceutical composition, comprising:the compound of Formula (I) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 8, and at least one pharmaceutically acceptable carrier or excipient; orthe compound of Formula (I’) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 9 to 15, and at least one pharmaceutically acceptable carrier or excipient;and optionally comprising a second therapeutic agent, e.g., an anticancer agent.

17. The compound of Formula (I) or Formula (I’) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 15, for use in the prevention and / or treatment of a disease or disorder associated with cereblon protein.

18. The compound of Formula (I) or Formula (I’) or a pharmaceutically acceptable salt thereof as claimed in claim 17, wherein the disease or disorder associated with cereblon protein is selected from the group consisting of: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure, and diabetes.

19. The compound of Formula (I) or Formula (I’) or a pharmaceutically acceptable salt thereof as claimed in claim 17, wherein the disease or disorder associated with cereblon protein is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplantation-related cancer; neutropenia; leukemia, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myelogenous leukemia, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, leukemia-associated anemia, B-cell acute lymphoblastic leukemia, T-cell lymphocytic leukemia, T-cell acute lymphoblastic leukemia, lymphoma cell leukemia, monocytic leukemia, myelomonocytic leukemia; lymphoma, including diffuse large B-cell lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20 positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt’s lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin’s lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin’s lymphoma, refractory B-cell non-Hodgkin’s lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin’s lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer; inflammatory myofibroblastoma; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; ovarian cancer; bronchial cancer; prostate cancer; breast cancer, including triple negative breast cancer, sporadic breast cancer, and patients with Cowden syndrome; pancreatic cancer; central nervous system tumor; neuroblastoma; glioma; peripheral neuroepithelioma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumors; esophageal cancer;colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; metrocarcinoma; head and neck cancer; brain cancer; oral cancer; sarcoma, including rhabdomyosarcoma, various lipogenic tumors, Ewing’s sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; cholangiocarcinoma; bone cancer; cervical cancer; skin cancer; Richter syndrome (RS); sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren’s syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type I diabetes mellitus, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including Crohn’s disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, Acquired immunodeficiency syndrome (AIDS), COVID-19 novel coronavirus infection, gram-negative bacteria infection, gram-positive bacteria infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplantation rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular diseases (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ dysfunction caused by cachexia and septic shock; and acute liver failure.

20. Use of the compound of Formula (I) or Formula (I’) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1-15, or the pharmaceutical composition as claimed in claim 15, for the manufacture of a medicament for the prevention or treatment of a disease or disorder associated with cereblon protein.

21. A method for treating or preventing a disease or disorder associated with cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of the compound of Formula (I) or Formula (I’) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1-15, or the pharmaceutical composition as claimed in claim 16.

22. The use as claimed in claim 20, or the method as claimed in claim 21, wherein the disease or disorder associated with cereblon protein is selected from the group consisting of: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure, anddiabetes.

23. The use as claimed in claim 20, or the method as claimed in claim 21, wherein the disease or disorder associated with cereblon protein is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplantation-related cancer; neutropenia; leukemia, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myelogenous leukemia, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, leukemia-associated anemia, B-cell acute lymphoblastic leukemia, T-cell lymphocytic leukemia, T-cell acute lymphoblastic leukemia, lymphoma cell leukemia, monocytic leukemia, myelomonocytic leukemia; lymphoma, including diffuse large B-cell lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20 positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt’s lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin’s lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin’s lymphoma, refractory B-cell non-Hodgkin’s lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin’s lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer; inflammatory myofibroblastoma; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; ovarian cancer; bronchial cancer; prostate cancer; breast cancer, including triple negative breast cancer, sporadic breast cancer, and patients with Cowden syndrome; pancreatic cancer; central nervous system tumor; neuroblastoma; glioma; peripheral neuroepithelioma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumors; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; metrocarcinoma; head and neck cancer; brain cancer; oral cancer; sarcoma, including rhabdomyosarcoma, various lipogenic tumors, Ewing’s sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; cholangiocarcinoma; bone cancer; cervical cancer; skin cancer; Richter syndrome (RS); sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers,Kawasaki disease, polymyositis / dermatomyositis, Sjogren’s syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type I diabetes mellitus, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including Crohn’s disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, Acquired immunodeficiency syndrome (AIDS), COVID-19 novel coronavirus infection, gram-negative bacteria infection, gram-positive bacteria infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplantation rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular diseases (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ dysfunction caused by cachexia and septic shock; and acute liver failure.

24. A method for preparing the compound of Formula (I) as claimed in claim 1, comprising using a compound of Formula (M1) and a compound of Formula (M2) as starting materials to obtain the compound of Formula (I):wherein Ra1, Ra2, Ra3, Ra4, (Ra5)m, Z, R, ring B, ring C, (Rd2)n2, (Rd3)n3, and m1 are as defined in claim 1; andLERw3 represents CHO, COOH, or R=2  , wherein Rc2 is as defined in claim 1, and the group LErepresents Cl, Br, I, OMs, OTs, or ONs;wherein (1) -Rw1-Rw2 represents       (Rdi)m, and R represents       (Rdi)m ; orA! N-NH(2) -Rw1-Rw2 represents(Rd1 )n1and R represents(Rd1 )n1; or(3) -Rw1-Rw2 represents -NH-NH2, and R represents -NH-NH-; or(4) -Rw1-Rw2 represents(Rd4)n4and R represents(Rd4)n4wherein Rw, ring A1, (Rd1)n1, ring A2, and (Rd4)n4 are as defined in claim 1;wherein when Rw3 represents CHO, Rc3 and Rc4 represent H; orwhen Rw3 represents COOH, Rc3 and Rc4 together form a carbonyl group; orLEwhen Rw3 represents Rc2 , Rc3 represents H, and Rc4 represents Rc2.

25. The method as claimed in claim 24, wherein(1) when Rw3 represents CHO, the compound of Formula (M1) and the compound of Formula (M2) are subjected to a reductive amination reaction to give the compound of Formula (I), wherein Rc3 and Rc4 in the compound of Formula (I) represent H;(2) when Rw3 represents COOH, the compound of Formula (M1) and the compound of Formula (M2) are subjected to an amide condensation reaction to give the compound of Formula (I), wherein Rc3 and Rc4 in the compound of Formula (I) together form a carbonyl group; orLE(3) when Rw3 represents R- , the compound of Formula (M1) and the compound of Formula (M2) are subjected to an aminoalkylation reaction to give the compound of Formula (I), wherein in the compound of Formula (I), Rc3 represents H, and Rc4 represents Rc2.

26. The method as claimed in claim 24, whereinwhen -Rw1-Rw2 in the compound of Formula (M1) represents      (Rdi)m or (Rdi)m , thecompound of Formula (M1) is prepared by a reaction using the compound of Formula (M3) and the compound of Formula (M4) as starting materials,Y represents F or Br;W1 represents H, and W2 represents an amino protecting group; orW1 represents an amino protecting group, and W2 represents H.

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