Quinolinepiperazine derivatives, pharmaceutical compositions and uses thereof

Abstract

The present invention provides a novel compound of formula (A) or a stereoisomer, tautomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, wherein said compound of formula (A) in a pharmaceutical composition is used for the treatment of cancer, including lung cancer.

Description

[Technical Field]

[0001] The present invention relates to the field of anticancer compounds, and more particularly to novel anticancer compounds, quinolinepiperazine derivatives, represented by Formula A. The present invention further relates to methods for preparing Formula A, pharmaceutical compositions thereof, and their use as anticancer agents. [Background technology]

[0002] Cancer is a serious health problem that poses a major threat to the health of people worldwide. Doctors and scientists across continents collaborate to constantly find better ways to care for cancer patients. Global cancer statistics predict that the number of cancer cases will continue to increase. One way to curb this increase is to develop and research new drugs.

[0003] Over the past few years, there has been continuous progress in the development of anti-cancer drugs. A wide variety of new drugs, ranging from small molecules to artificial antibodies and immunomodulators, have been approved for cancer treatment. Drugs undergo a long development process and approval process before they can be prescribed to patients.

[0004] The development of a new drug involves three main steps: preclinical research, which is when a drug is discovered and first tested; clinical research, which tests the drug on humans; and postclinical research, which is the ongoing study of a drug after it has been approved.

[0005] Preclinical research in most drug discovery programs begins with biochemical, virtual, or biophysical screening of agonists, antagonists, or inhibitors of specific disease-related targets. This drug discovery program, commonly referred to as target-based drug discovery (TDD), begins with a defined molecular target hypothesized to play a key role in disease through advances in molecular biology and genomics. These compounds are then chemically optimized based on their desired efficacy. These compounds must then be further refined to yield derivatives with improved potency and / or selectivity and desirable pharmacokinetic properties. Selected drug candidates are then tested in vivo, and once their safety and efficacy are confirmed, they proceed to the second phase of clinical research, or human clinical trials. This is followed by regulatory approval and marketing at the state level. Clinical trials are used to determine whether a new drug is safe, effective, and superior to standard treatments. Before approval by regulatory agencies such as the FDA, a drug must undergo three phases of clinical trials. The initial phase of clinical trials focuses on drug safety, dosage, and how the drug is processed in the body. Later phases will examine how well the drug works, with each phase involving more people than the previous one.

[0006] This well-defined process often requires years of research and significant resources, generally resulting in low success rates in cancer drug development. Furthermore, these traditional target-based drug discovery (TDD) methods are not adequately adapted to pathologies resulting from the simultaneous or sequential action of multiple etiologies, such as cancer. [1,2] Furthermore, many of these drugs still cause serious side effects. In cancer drug development, up to 95% of drugs tested in Phase I trials fail to achieve marketing approval, making the drug development process costly, inefficient, and often abandoned.

[0007] The obstacles faced by traditional drug discovery methods have led to outside-the-box thinking and increased interest in phenotypic drug discovery (PDD) approaches. PDD approaches do not rely on knowledge of the identity of a specific drug target or hypotheses about its role in disease. [3,4] PDD approaches are effective tools for addressing the complexities of diseases that are not fully understood by the scientific community.

[0008] The present invention provides novel anticancer compounds designed using a combination of databases, including a small molecule database. Target and disease databases were used to identify off-target binding, target-based toxicity, drug repurposing, and compound-target binding patterns. Computational tools were integrated to understand binding patterns and identify quantum mechanical properties of the molecules. ADMET (adsorption, distribution, metabolism, excretion, toxicity) models were also generated to optimize the molecules. Several classes of small molecules were created. The present invention provides a novel class of compounds, quinolinepiperazine derivatives, with anticancer properties. Objectives of the Invention

[0009] The primary object of the present invention is to provide novel compounds, quinolinepiperazine derivatives, represented by formula A, as well as optically active forms, racemic mixtures, polymorphs, tautomers, solvates, hydrates, complexes, pharmaceutically acceptable salts and stereoisomers thereof. [ka] wherein R1, R2, R3, R4, R5, R6, R7, and R8 are selected from the group consisting of the formulae provided in Table 1, thereby resulting in various derivatives of parent molecular formula A, and m=0 and n=0.

[0010] Another object of the present invention is to provide novel compounds having anti-cancer properties, novel compounds represented by formula A, quinolinepiperazine derivatives, and their pharmaceutical uses.

[0011] It is yet another object of the present invention to provide a method for preparing the novel compound, quinolinepiperazine derivative, represented by formula A. Summary of the Invention

[0012] In its main embodiment, the present invention provides a novel compound represented by formula A, a quinolinepiperazine derivative, or a stereoisomer of said compound, or a pharmaceutically acceptable salt thereof. [ka] wherein R1, R2, R3, R4, R5, R6, R7, and R8 are selected from the group consisting of the formulae provided in Table 1, thereby resulting in various derivatives of parent molecular formula A, and m=0 and n=0. Table 1 is a list of formulas represented by R1 to R8. [Table 1-1] [Table 1-2]

[0013] In another embodiment of the present invention, there is provided a quinolinepiperazine derivative of formula A, or a stereoisomer of said compound, or a pharmaceutically acceptable salt thereof, having anticancer properties.

[0014] In yet another embodiment, the present invention provides a method for preparing a quinolinepiperazine derivative of formula A. [Brief explanation of the drawings]

[0015] [Figure 1]Figure 1a shows the cytotoxicity curve of compound A1 against the A549 cell line; Figure 1b shows the cytotoxicity curve of compound A7 against the A549 cell line; Figure 1c shows the cytotoxicity curve of compound A42 against the A549 cell line; Figure 1d shows the cytotoxicity curve of compound A43 against the A549 cell line; Figure 1f shows the cytotoxicity curve of compound A48 against the A549 cell line; and Figure 1g shows the cytotoxicity curve of compound A49 against the A549 cell line. [Figure 2] Figure 2a shows the cytotoxicity curve of compound A1 against the Ncl-H460 cell line; Figure 2b shows the cytotoxicity curve of compound A7 against the Ncl-H460 cell line; Figure 2c shows the cytotoxicity curve of compound A42 against the Ncl-H460 cell line; Figure 2d shows the cytotoxicity curve of compound A43 against the Ncl-H460 cell line; Figure 2f shows the cytotoxicity curve of compound A48 against the Ncl-H460 cell line; and Figure 2g shows the cytotoxicity curve of compound A49 against the Ncl-H460 cell line. [Figure 3] Figure 3a shows the cytotoxicity curve of compound A1 against the Ncl-H522 cell line; Figure 3b shows the cytotoxicity curve of compound A7 against the Ncl-H522 cell line; Figure 3c shows the cytotoxicity curve of compound A42 against the Ncl-H522 cell line; Figure 3d shows the cytotoxicity curve of compound A43 against the Ncl-H522 cell line; Figure 3f shows the cytotoxicity curve of compound A48 against the Ncl-H522 cell line; and Figure 3g shows the cytotoxicity curve of compound A49 against the Ncl-H522 cell line. Detailed Description of the Invention

[0016] The present invention will now be described in detail with reference to the detailed description, which illustrates only some, but not all, embodiments of the present invention. Indeed, the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Like numbers refer to like elements throughout. The present invention is described fully herein, along with non-limiting embodiments and illustrative experiments. For purposes of determining infringement, the scope of the present invention includes any one or more of the appended claims, including equivalents of the subject matter, elements, or limitations described herein.

[0017] The present invention therefore provides a compound of formula A: [ka] wherein R1, R2, R3, R4, R5, R6, R7, and R8 are selected from the group consisting of the formulas provided in Table 1, resulting in various derivatives of parent molecular formula A, and m=0 and n=0.

[0018] Thus, in a first embodiment, the present invention includes compounds according to Table 2. Table 2: List of derivatives of formula A [Table 2-1-1] [Table 2-1-2] [Table 2-1-3] [Table 2-1-4] [Table 2-1-5] [Table 2-1-6] [Table 2-1-7] [Table 2-1-8] [Table 2-1-9] [Table 2-1-10] [Table 2-1-11] [Table 2-1-12] [Table 2-1-13] [Table 2-1-14] [Table 2-1-15] [Table 2-1-16] [Table 2-1-17]

[0019] [Table 2-2-1] [Table 2-2-2] [Table 2-2-3]

[0020] In a preferred embodiment of the present invention, in formula A: R1 is [ka] R2 is [ka] There is provided a compound of Formula A, where R3 is CF3, R4 is H, R5 is H, R6 is H, R7 is H, R8 is H, m=0 and n=0, which has the chemical structure represented by Compound A1. [ka] Compound A1 {4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-(trifluoromethyl)pyridin-2-amine}

[0021] In another embodiment, the present invention provides a compound of formula A, wherein: R1 is [ka] R2 is [ka] There is provided a compound of formula A, where R3 is CF3, R4 is H, R5 is H, R6 is H, R7 is H, R8 is H, m=0, and n=0, which has the chemical structure represented by compound A7. [ka] Compound A7 {4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(5-methoxypyridin-3-yl)-6-(trifluoromethyl)pyrimidin-2-amine)

[0022] In another embodiment, the present invention provides a compound of formula A, wherein: R1 is [ka] R2 is [ka] There is provided a compound of Formula A, where R3 is CH3, R4 is H, R5 is H, R6 is H, R7 is H, R8 is H, m=0, and n=0, which has the chemical structure represented by Compound A42. [ka] Compound A42 {N-(3,5-dimethoxyphenyl)-4-methyl-6-(4-(quinolin-4-yl)piperazin-1-yl)pyrimidin-2-amine)

[0023] In another embodiment, the present invention provides a compound of formula A, R1 is [ka] R2 is [ka] There is provided a compound of Formula A, where R3 is CF3, R4 is H, R5 is H, R6 is H, R7 is H, R8 is H, m=0, and n=0, which has the chemical structure represented by Compound A43. [ka] Compound A43 {N-(3,5-dimethoxyphenyl)-4-(4-(quinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine}

[0024] In another embodiment, the present invention provides a compound of formula A, R1 is [ka] R2 is [ka] There is provided a compound of Formula A, where R3 is CH3, R4 is H, R5 is H, R6 is H, R7 is H, R8 is H, m=0, and n=0, which has the chemical structure represented by Compound A48. [ka] Compound A48 {N-(3,5-dimethoxyphenyl)-4-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-amine}

[0025] In another embodiment, the present invention provides a compound of formula A, R1 is [ka] R2 is [ka] There is provided a compound of Formula A, where R3 is CF3, R4 is H, R5 is H, R6 is H, R7 is H, R8 is H, m=0, and n=0, which has the chemical structure designated compound A49. [ka] Compound A49 {N-(3,5-dimethoxyphenyl)-4-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine} [Example]

[0026] Example 1 Quinolinepiperazine derivatives, their preparation and properties General procedure for the synthesis of intermediates 3a-3ap In a well-dried round-bottom flask, 1a-1ab (1 equiv.) was dissolved in ethanol. Compounds 2a-2g were added portionwise and stirred at 70 °C for 12 h. The progress of the reaction was monitored by TLC. Upon completion of the reaction, ethanol was evaporated under vacuum, and the reaction mixture was washed with NaHCO3 solution and extracted with DCM (3 × 20 mL). The three extracted fractions were combined, dried over Na2SO4, and concentrated to give the desired compound. Table 3: List of intermediates 3a-3ap [Table 3-1] [Table 3-2]

[0027] General procedure for the synthesis of intermediates 5a-5be Intermediate 3a-3ap was placed in a well-dried round-bottom flask and dissolved in ethanol, followed by the addition of 4a-4h at 0 °C. The reaction mixture was then stirred at room temperature for 4 h. The reaction progress was monitored by TLC. After completion of the reaction, ethanol was evaporated under reduced pressure, and the residue was washed with NaHCO3 solution and extracted with DCM (3 × 20 mL). The combined organic fractions were collected, dried over Na2SO4, and concentrated on a rotary evaporator. The crude compound was purified by column chromatography using ethyl acetate:hexane (3:7) as the eluent to obtain the desired compound. Table 4: List of intermediates 5a-5be [Table 4-1] [Table 4-2] [Table 4-3]

[0028] A2, A3, A4, A5, A10, A27, A28, A29, A30, A31, A32, A39, A41, A42, A44, A46, A48, A51, A53, A54, A55, A56, General synthetic procedure for A57, A58, A59, A60, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A80, A81, A82, A83, A84, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A99, A101, A102, A103, A104, A105, A106, A108, A110, A111, A112, A115, A116, A117 Intermediates 5b, 5c, 5d, 5f, 5h, 5j, 5m, 5o, 5p, 5q, 5v, 5w, 5x, 5y, 5z, 5aa, 5ba, 5r, 5s, 5t, 5u, 5ac, 5az, 5ab, 5ad, 5ae, 5af, 5ag, 5ah, 5ai, 5aj, 5ak, 5al, 5am, 5an, 5ao, 5aw, 5be, 5ap, 5aq, 5au, 5ar, 5bb, 5bc, 5aq, 5bd, 5as, 5at, and 5au (1 equiv.)) were placed in a dry round-bottom flask and dissolved in isopropanol. Subsequently, an aromatic amine (1.1 equiv.) was added. A catalytic amount of concentrated HCl was added, and the reaction mixture was refluxed at 100 °C for 12 h. The reaction progress was monitored by thin-layer chromatography (TLC). Upon completion, the reaction mixture was concentrated in vacuo. The residue was treated with NaHCO3 solution and extracted with dichloromethane (DCM) (3 x 15 mL). The combined organic layers were washed with brine solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude compound was then purified by column chromatography to give the desired product.

[0029] General procedure for the synthesis of A1, A6, A7, A8, A9, A33, A34, A35, A36, A37, A38, A40, A43, A45, A47, A49, A50, A52, A96, A107, A109, A113, A114 5a, 5e, 5g, 5i, 5k, 5l, 5n, 5av, 5ax, 5ay, and 5aw (1 equivalent) were placed in a well-dried round-bottom flask and dissolved in 1,4-dioxane, followed by the addition of an aromatic amine (1.1 equivalents).t Bu (1 equiv.) was added, followed by a catalytic amount of Pd( t Bu3P2 was added and the reaction mixture was refluxed at 100 °C for 12 h. The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated in vacuo. The crude compound was then purified by column chromatography to give the desired compound.

[0030] General procedure for the synthesis of A19, A20, A21, A22, A23, A24, A25, A26, A97, and A98 Intermediates 5a, 5aw, and 5ax (1 equivalent) were placed in a dry round-bottom flask and dissolved in N,N-dimethylformamide. An aliphatic amine (3 equivalents) was then added. The reaction mixture was then refluxed at 110°C for 12 hours. The reaction progress was monitored by TLC. After completion, the reaction mixture was cooled to room temperature. 30-40 mL of water was added, and the resulting residue was filtered and washed with excess cold water to obtain the desired compound.

[0031] General procedure for the synthesis of A11, A12, A13, A14, A15, A16, A17, A18, A61, A62, A63, A64, A65, A66, A98, A100, A102 Intermediates 5b, 5ay, and 5ba (1 equiv.) were placed in a dry round-bottom flask and dissolved in N,N-dimethylformamide, followed by the addition of an aliphatic amine (3 equiv.). The reaction mixture was then stirred at 110 °C for 12 h. The reaction progress was monitored by TLC. Upon completion, the reaction mixture was cooled to room temperature. 30–40 mL of water was added to the mixture. The crude compound was filtered, washed with excess cold water, and purified by column chromatography to obtain the desired product.

[0032] Compound analytical data:

[0033] Compound-A1: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-(trifluoromethyl)pyridin-2-amine: 1H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(s,1H), 7.36(d,1H), 6.44(d, 1H), 5.77(d,1H), 5.73(s,2H), 5.74(d,1H), 4.00(s,1H), 3.83(s,6H), 3.28(s,8H); 13 C-NMR-400-MHz-DMSO:160.6, 159.4, 159.2, 155.0, 153.0, 150.8, 144.4, 147.3, 135.6, 130. 1, 128.6, 126.0, 122.6, 119.7, 118.3, 98.9, 92.9, 91.7, 90.4, 55.8, 49.8, 48.5; Molecular weight: 490.188

[0034] Compound-A2: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3-methoxy-5-(trifluoromethyl)phenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.43(d,1H), 8.70(d,1H), 7.74(d,1H), 7.38(d,1H), 6 .82(d,2H), 6.74(d,1H), 5.82(s,1H), 3.81(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 161.7, 159.2, 153.0, 150.8, 143.7, 135.6, 132.8, 130 .1, 128.9, 126.0, 124.4, 122.6, 118.6, 108.3, 102.7, 99.2, 55.8, 49.8, 48.5, 23.9; molecular weight: 528.165

[0035] Compound-A3: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(5-methoxypyridin-3-yl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.70(d,1H), 8.45(d,1H), 8.18(s,1H), 7.93(s,1H), 7.80(s,1H), 7.74(d, 1H), 7.38(d,1H), 6.89(d,1H), 6.74(s,1H), 5.82(s,1H), 3.83(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 159.2, 156.1, 153.0, 150.8, 135.6, 134.2, 130 .0, 126.9, 126.0, 122.6, 121.1, 118.3, 105.3, 93.8, 55.8, 49.8, 48.5, 23.9; Molecular weight: 461.173.

[0036] Compound-A4: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3-methoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.43(d,1H), 8.70(d,1H), 8.45(d,1H), 7.74(d,1H), 7.38(d,1H), 7.21(t, 1H), 6.82(d,1H), 6.74(t,1H), 6.49(t,1H), 5.82(s,1H), 3.74(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 12 9.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 460.966.

[0037] Compound-A5: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3-fluoro-5-methoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:9.43(s,1H), 8.70(d,1H), 8.45(d,1H), 7.74(d,1H), 7.38(d,1H), 7 .21(t,1H), 6.79(m,2H), 6.59(t,1H), 5.82(s,1H), 3.81(s,3H), 3.28(s,8H)2.42(s, 3H); 13 C-NMR-400-MHz- DMSO:170.2, 168.0, 164.5, 163.0, 159.2, 153.0, 150.8, 145.0, 135.6, 130.1, 128 .9, 126.0, 122.6, 118.3, 97.1, 95.0, 92.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 478.168.

[0038] Compound-A6: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3-methoxy-5-(trifluoromethyl)phenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.43(s,1H), 8.70(d,1H), 8.45(d,1H), 7.74(d,1H), 7.38(d,1H), 7 .21(t,1H), 6.79(m,2H), 6.59(t,1H), 5.82(s,1H), 3.81(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 582.137.

[0039] Compound-A7: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(5-methoxypyridin-3-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:9.43(s,1H), 8.70(d,1H), 8.45(d,1H), 7.74(d,1H), 7.38(d,1H), 7 .21(t,1H), 6.79(m,2H), 6.59(t,1H), 5.82(s,1H), 3.81(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 515.145.

[0040] Compound-A8: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3-methoxyphenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO: 9.43(s,1H), 8.70(d,1H), 8.45(d,1H), 7.74(d,1H), 7.38(d,1H), 7.21(t,1H), 6.79(m,2H), 6.59(t,1H), 5.82(s,1H), 3.81(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 514.937.

[0041] Compound-A9: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3-fluoro-5-methoxyphenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1H-NMR-400MHz-:9.43(s,1H), 8.70(d,1H), 8.45(d,1H), 7.74(d,1H), 7.38(d,1H), 7.21 (t,1H), 6.79(m,2H), 6.59(t,1H), 5.82(s,1H), 3.81(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 1 29.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 532.147.

[0042] Compound-A10: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyridin-2-amine: 1 H-NMR-400-MHz-DMSO:9.43(s,1H), 8.70(d,1H), 8.45(d,1H), 7.74(d,1H), 7.38(d,1H), 7 .21(t,1H), 6.79(m,2H), 6.59(t,1H), 5.82(s,1H), 3.81(s,3H), 3.28(s,8H), 2.42(s,3H); 13 C-NMR-400-MHz-DMSO:160.6, 159.4, 159.2, 155.0, 153.0, 150.8, 144.4, 130.1, 128. 9, 126.0, 122.6, 118.3, 98.9, 92.9, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 455.16.

[0043] Compound-A11: 7-chloro-4-(4-(6-methyl-2-(pyrrolidin-1-yl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1H-NMR-400-MHz-DMSO:8.74(d,1H), 8.15(d,1H), 8.01(d,1H), 7.59(dd,1H), 7.06(d ,1H), 6.38(s,1H), 3.9(s,4H), 3.51(d,4H), 3.31(s,1H), 2.28(s,3H), 1.93(s,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 408.18.

[0044] Compound-A12: 7-chloro-4-(4-(6-methyl-2-(piperidin-1-yl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1 H-NMR-400-MHz-DMSO:8.73(dd,1H), 8.14(q,1H), 8.01(dd,1H), 7.59(m,1H), 7.10(dd,1H), 6.01( s,1H), 3.80(s,4H), 3.68(t,4H), 3.50(s,1H), 3.23(t,4H), 2.10(s,3H), 1.58(t,2H), 1.49(t,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 422.20.

[0045] Compound-A13: 4-(4-(2-(azepan-1-yl)-6-methylpyrimidin-4-yl)piperazin-1-yl)-7-chloroquinoline: 1H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(dd,1H), 6.44(d ,1H), 5.82(d,1H), 3.68(t,4H), 3.80(s,8H), 2.33(s,3H), 1.74(t,4H), 1.60(t,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 436.21.

[0046] Compound-A14: 7-chloro-4-(4-(6-methyl-2-(piperazin-1-yl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(dd,1H), 6.44(d ,1H), 5.82(d,1H), 3.17(t,4H), 3.80(s,8H), 2.33(s,3H), 2.78(t,4H), 1.91(s,1H); 13 C-NMR-400MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 423.19.

[0047] Compound-A15: 7-chloro-4-(4-(6-methyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(dd,1H), 6.44(d ,1H), 5.82(d,1H), 3.15(t,4H), 3.37(s,8H), 2.33(s,3H), 2.36(t,4H), 2.26(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 437.21.

[0048] Compound-A16: 4-(4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)morpholine: 1 H-NMR-400-MHz-DMSO:8.74(d,1H), 8.13(dd,1H), 8.00(d,1H), 7.58(dd,1H), 7.05(d,1H), 6.11(s,1H), 3.82(s,4H), 3.62(s,8H), 3.23(t,4H), 2.10(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 424.18.

[0049] Compound-A17: 4-(4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)thiomorpholine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.63(d,1H), 7.36(dd ,1H), 6.44(d,1H), 5.82(d,1H), 3.43(t,4H), 3.87(s,8H), 2.33(s,3H), 2.67(t,4H);13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 440.15.

[0050] Compound-A18: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-cyclohexyl-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.70(d,1H), 8.45(d,1H), 7.74(s,1H), 7.73(d,1H), 6.74(d,1H), 5.95(s, 1H), 5.82(s,1H), 3.28(t,8H), 2.57(p,1H), 2.42(s,3H), 1.71(m,2H), 1.46(m,4H), 1.21(m,4H); 13 C-NMR-400-MHz-DMSO:170.2, 164.5, 160.6, 159.2, 153.0, 150.8, 135.6, 130.1, 128. 9, 126.0, 122.6, 118.3, 93.8, 54.7, 49.8, 48.5, 32.9, 25.7, 25.1, 23.9; Molecular weight: 436.214.

[0051] Compound-A19: 7-chloro-4-(4-(2-(pyrrolidin-1-yl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1 H-NMR-400-MHz-DMSO:8.73(d,1H), 8.14(d,1H), 8.01(d,1H), 7.59(dd,1H), 7 .05(d,1H), 6.53(s,1H), 3.94(s,4H), 3.47(s,4H), 3.25(t,4H), 1.90(t,4H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 462.17.

[0052] Compound-A20: 7-chloro-4-(4-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1 H-NMR-400-MHz-DMSO:8.73(d,1H), 8.13(d,1H), 8.00(d,1H), 7.58(dd,1H), 7.05(d ,1H), 6.52(s,1H), 3.93(s,4H), 3.71(t,4H), 3.26(t,4H), 1.61(d,2H), 1.52(d,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 476.17.

[0053] Compound-A21: 4-(4-(2-(azepan-1-yl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)-7-chloroquinoline: 1 H-NMR-400-MHz-DMSO:8.73(d,1H), 8.13(d,1H), 8.01(d,1H), 7.58(dd,1H), 7 .06(d,1H), 6.51(s,1H), 3.93(s,4H), 3.68(t,4H), 1.70(s,4H), 1.48(t,4H); 13C-NMR-400MHZ-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 490.19.

[0054] Compound-A22: 7-chloro-4-(4-(2-(piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1 H-NMR-400-MHz-DMSO:8.73(d,1H), 8.13(dd,1H), 8.01(d,1H), 7.58(dd,1H), 7.06(d,1H), 6.55(s,1H), 3.93(s,4H), 3.25(t,4H), 2.71(t,4H); 13 C-NMR-400MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 490.19.

[0055] Compound-A23: 7-chloro-4-(4-(2-(4-methylpiperazin-1-yl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)quinoline: 1 H-NMR-400-MHz-DMSO:8.73(d,1H), 8.13(dd,1H), 8.01(d,1H), 7.58(dd,1H), 7.06(d ,1H), 6.58(s,1H), 3.94(s,4H), 3.70(t,4H), 3.26(t,4H), 2.34(t,4H), 2.20(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 490.18.

[0056] Compound-A24: 4-(4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)morpholine: 1 H-NMR-400-MHz-DMSO:8.73(d,1H), 8.13(dd,1H), 8.01(d,1H), 7.59(dd,1H), 7.06(d,1H), 6.62(s,1H), 3.95(s,4H), 3.65(m,8H), 3.26(t,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 490.18.

[0057] Compound-A25: 4-(4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)thiomorpholine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.63(d,1H), 7. 36(dd,1H), 6.44(d,1H), 5.82(d,1H), 3.43(t,4H), 3.67(s,8H), 2.67(t,4H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 494.19.

[0058] Compound-A26: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-cyclohexyl-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.70(d,1H), 8.45(d,1H), 7.74(s,1H), 7.73(d,1H), 6.74(d,1H), 5.95(s, 1H), 5.82(s,1H), 4.00(s,1H), 3.28(t,8H), 2.57(p,1H), 1.71(m,2H), 1.46(m,4H), 1.21(m,4H); 13 C-NMR-400-MHz-DMSO:170.2, 160.5, 159.2, 154.7, 153.0, 150.8, 135.6, 130.1, 12 8.9, 126.0, 122.6, 119.7, 93.8, 54.7, 49.8, 48.5, 32.9, 25.7, 25.1; Molecular weight: 490.186.

[0059] Compound-A27: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(2,6-difluorophenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 6.76(dd,2H), 6.64(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 466.16.

[0060] Compound-A28: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(5-fluoropyridin-2-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 6.76(dd,2H), 6.64(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13 C-NMR-400MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 449.19.

[0061] Compound-A29: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(pyridin-2-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 6.76(dd,2H), 6.64(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 431.16

[0062] Compound-A30: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(pyridin-4-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 6.76(dd,2H), 6.64(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 431.16.

[0063] Compound-A31: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(2,3-dichlorophenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 6.76(dd,2H), 6.64(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 498.02.

[0064] Compound-A32: N-(3-bromophenyl)-4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 6.76(dd,2H), 6.64(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 508.08.

[0065] Compound-A33: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(2,6-difluorophenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.10(s,1H), 8.71(d,1H), 8.12(d,1H), 8.00(d,1H), 7.57(dd ,1H), 7.29(q,1H), 7.14(t,1H), 7.04(s,2H), 6.74(s,1H), 3.86(s,4H), 3.21(s,4H); 13C-NMR-400MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 520.12.

[0066] Compound-A34: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(5-fluoropyridin-2-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6 .44(d,1H), 5.82(d,1H), 6.76(dd,2H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 1 29.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6. Molecular weight: 503.12.

[0067] Compound-A35: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(pyridin-2-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1H-NMR-400-MHz-DMSO: 8.36 (d,1H), 8.23 ​​(d,1H), 8.07 (d,1H), 7.87 (dd,1H), 7.36 (d,1H), 6.44 (d,1H), 5.82 (d,1H), 6.62 (d,1H), 6.83 (d,2H), 7.55 (d,1H), 4.00 (s,1H), 3.90 (s,8H), 3.83 (s,3H), 2.33 (s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 485.13.

[0068] Compound-A36: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(pyridin-4-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:10.08(s,1H), 8.74(t,1H), 8.36(d,1H), 8.17(d,1H), 8 .02(t,1H), 7.70(d,2H), 7.61(dd,1H), 6.99(d,1H), 4.08(s,4H), 3.31(s,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 485.13.

[0069] Compound-A37: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(2,3-dichlorophenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 8.08(d,1H), 6.44(d,1H), 5 .82(d,1H), 7.02(d,1H), 7.15(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 552.06.

[0070] Compound-A38: N-(3-bromophenyl)-4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d, 1H), 6.94(dd,2H), 6.69(d,1H), 6.96(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,3H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 562.06.

[0071] Compound-A39: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methyl-N-phenylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.02(s,1H), 8.74(d,1H), 8.16(d,1H), 8.01(d,1H), 7.73(dd,1H), 7 .23(q,2H), 7.07(d,1H), 6.87(m,1H), 6.24(s,1H), 3.89(s,4H), 3.28(s,4H), 2.23(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 430.17.

[0072] Compound-A40: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-phenyl-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.74(d,1H), 8.16(d,1H), 8.01(d,1H), 7.73(dd,2H), 7.60(dd ,1H), 7.28(m,1H), 7.07(d,1H), 6.93(t,1H), 6.76(s,1H), 4.01(s,4H), 3.29(s,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 484.14.

[0073] Compound-A41: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.05(s,1H), 8.73(d,1H), 8.16(d,1H), 8.02(q,2H), 7.60(dd ,1H), 7.05(t,3H), 6.36(d,1H), 6.06(s,1H), 3.92(s,4H), 3.70(s,6H), 3.30(d,4H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 476.17.

[0074] Compound-A42: N-(3,5-dimethoxyphenyl)-4-methyl-6-(4-(quinolin-4-yl)piperazin-1-yl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.05(s,1H), 8.71(d,1H), 8.16(d,1H), 7.97(dd,1H), 7.76(t,1H), 7 .60(m,1H), 7.07(t,3H), 6.26(s,1H), 6.04(t,1H), 3.92(s,4H), 3.71(d,6H), 3.32(s,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 456.23.

[0075] Compound-A43: N-(3,5-dimethoxyphenyl)-4-(4-(quinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.17(d,1H), 7.92(t,1H), 7.76(dd,1H), 7.59(t,1H), 6.44(d ,1H), 5.82(d,1H), 5.73(s,2H), 5.74(d,1H), 4.00(s,1H), 3.83(s,6H), 3.28(s,8H), 3.32(s,4H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 456.23.

[0076] Compound-A44: N-(3,5-dimethoxyphenyl)-4-methyl-6-(4-(7-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:10.03(s,1H), 8.82(d,1H), 8.47(d,1H), 8.38(s,1H), 7.93(d,1H), 7 .24(d,1H), 6.79(s,1H), 6.60(s,1H), 6.29(s,1H), 4.00(d,8H), 3.73(s,6H), 2.35(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 1 29.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 524.21.

[0077] Compound-A45: N-(3,5-dimethoxyphenyl)-4-(trifluoromethyl)-6-(4-(7-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:10.03(s,1H), 8.82(d,1H), 8.47(d,1H), 8.38(s,1H), 7.93(d,1H), 7 .24(d,1H), 6.79(s,2H), 6.60(s,1H), 6.29(s,1H), 4.00(d,8H), 3.73(s,6H), 2.35(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.0, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 12 9.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5; Molecular weight: 578.19.

[0078] Compound-A46: N-(3,5-dimethoxyphenyl)-4-methyl-6-(4-(quinazolin-4-yl)piperazin-1-yl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.49(s,1H), 8.16(d,1H), 7.84(t,1H), 7.83(t,1H), 7.58(t,1H), 5 .82(d,1H), 5.73(s,2H), 5.74(d,1H), 4.00(s,1H), 3.83(s,6H), 3.28(s,8H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:179.6, 170.2, 168.0, 164.5, 160.6, 156.6, 151.4, 144.4, 1 32.7, 129.5, 127.4, 122.5, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 457.22.

[0079] Compound-A47: N-(3,5-dimethoxyphenyl)-4-(4-(quinazolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.49(s,1H), 8.16(d,1H), 7.84(t,1H), 7.83(t,1H), 7.58(t, 1H), 5.82(d,1H), 5.73(s,2H), 5.74(d,1H), 4.00(s,1H), 3.83(s,6H), 3.28(s,8H); 13 C-NMR-400-MHz-DMSO:179.6, 170.2, 168.0, 160.6, 156.6, 154.7, 151.7, 144.4 , 131.9, 127.4, 122.2, 119.7, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5; Molecular weight: 511.19.

[0080] Compound-A48: N-(3,5-dimethoxyphenyl)-4-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:11.94(s,1H), 9.06(s,1H), 8.66(s,1H), 8.12(d,1H), 7.83(q,2H), 7.58(m ,1H), 7.07(d,2H), 6.02(s,1H), 6.04(s,1H), 3.89(s,8H), 3.70(s,6H), 2.22(s,3H), 1.90(s,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 163.8, 160.6, 159.4, 153.0, 149.5, 144.4, 127. 5, 124.9, 128.4, 117.4, 116.7, 113.2, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 511.19.

[0081] Compound-A49: N-(3,5-dimethoxyphenyl)-4-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.56(s,1H), 8.73(d,1H), 8.21(q,1H), 7.70(dd,1H), 7.51(m,1H), 7.03(q ,4H), 6.79(s,1H), 6.11(t,1H), 5.75(s,1H), 4.04(s,4H), 3.70(s,6H), 3.39(q,2H), 1.09(t,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 163.8, 160.6, 159.4, 154.7, 153.0, 149.5, 144.4 , 127.5, 124.9, 119.7, 117.4, 113.2, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5; Molecular weight: 528.19.

[0082] Compound-A50: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-(trifluoromethyl)pyridin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(s,1H), 7.36(d,1H), 6.44(d, 1H), 5.77(d,1H), 5.73(s,2H), 5.74(d,1H), 4.00(s,1H), 3.83(s,6H), 3.28(s,8H); 13 C-NMR-400-MHz-DMSO:160.6, 159.4, 159.2, 155.0, 153.0, 150.8, 144.4, 147.3, 135.6, 130. 1, 128.6, 126.0, 122.6, 119.7, 118.3, 98.9, 92.9, 91.7, 90.4, 55.8, 49.8, 48.5; Molecular weight: 543.16.

[0083] Compound-A51: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyridin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(s,1H), 7.36(d,1H), 6.44(d,1H), 5 .77(d,1H), 5.73(s,2H), 5.74(d,1H), 4.00(s,1H), 3.83(s,6H), 3.28(s,8H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:160.6, 159.4, 159.2, 155.0, 153.0, 150.8, 144.4, 130.1, 128. 9, 126.0, 122.6, 118.3, 98.9, 92.9, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 489.19.

[0084] Compound-A52: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-fluoropyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.01(d,1H), 7.62(d,1H), 7.57(d,1H), 7.32(dd,1H), 7.38(d,1H), 6.98(d,1H) ), 5.74(s,1H), 5.74(s,1H), 5.73(s,1H), 5.26(d,1H), 3.83(s,6H), 4.00(s,1H), 3.57(t,4H), 3.28; 13 C-NMR-400-MHz-DMSO:176.1, 166.9, 160.6, 159.4, 159.2, 153.0, 150.8, 144.4, 135.6 , 130.1, 128.9, 126.0, 122.6, 118.3, 91.7, 90.4, 83.0, 55.8, 49.8, 48.5; Molecular weight: 494.19.

[0085] Compound-A53: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-5-fluoro-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(dd,1H), 6.44(d ,1H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,6H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:164.1, 160.6, 159.2, 157.2, 153.0, 150.8, 130.0, 135.6 , 130.1, 118.3, 122.6, 118.3, 93.8, 90.4, 55.8, 49.8, 48.5, 15.3; Molecular weight: 508.18.

[0086] Compound-A54: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(2,6-difluoro-3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(s,1H), 7.36(d,1H), 6.44(d, 1H), 5.82(d,1H), 5.90(d,1H), 4.00(s,1H), 3.30(s,8H), 3.83(s,6H), 2.33(s,3H); 13 C-NMR-400MHz-DMSO:170.2, 168.0, 164.5, 163.0, 159.2, 158.5, 153.0, 150.8, 145.6, 135.6, 13 0.1, 128.9, 126.0, 122.6, 118.3, 100.4, 94.7, 93.4, 92.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 526.17.

[0087] Compound-A55: 4-(4-(6,7-difluoroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 7.68(d,1H), 7.36(dd,1H), 6.44(d,1H), 5.74(d ,2H), 5.73(d,1H), 5.82(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,6H), 2.33(s,3H); 13 C-NMR-400MHz-DMSO:170.2, 168.0, 164.5, 160.6, 158.8, 154.4, 152.3, 151.3, 146.5, 14 4.4, 125.4, 118.4, 115.6, 109.4, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 526.17.

[0088] Compound-A56: 4-(4-(7-chloro-6-fluoroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.36(d,1H), 7.85(d,1H), 7.32(dd,1H), 6.44(d,1H), 5.74(d ,2H), 5.73(d,1H), 5.82(d,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,6H), 2.33(s,3H); 13 C-NMR-400MHz-DMSO:170.2, 168.0, 164.5, 161.7, 160.6, 158.6, 152.3, 147.8, 144.4, 13 2.5, 126.5, 125.7, 119.4, 108.2, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 508.18.

[0089] Compound-A57: 4-(4-(7-chloro-4a,5,6,7,8,8a-hexahydroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:7.50(d,1H), 5.82(d,1H), 5.74(d,2H), 5.73(d,1H), 4.96(m,1H), 4.49(d,1H), 4.00(s,1H), 3. 83(s,6H), 3.65(t,4H), 3.42(m,3H), 2.78(t,4H), 2.33(s,3H), 2.10(q,1H), 1.70(m,2H), 1.60(m,2H), 1.40(m,2H).: 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 162.1, 160.6, 144.4, 93.8, 91.7, 90.4, 93.8, 59.6, 55.8, 53.7, 53.5, 47.0, 37.9, 36.2, 23.9, 19.2; Molecular weight: 496.24.

[0090] Compound-A58: 4-(4-(7-chloro-2-methyl-4a,5,6,7,8,8a-hexahydroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:5.82(d,1H), 5.74(d,2H), 5.73(d,1H), 4.96(m,1H), 4.49(d,1H), 4.00(s,1H), 3.83(s,6H), 3 .65(t,4H), 3.42(m,3H), 2.78(t,4H), 2.33(s,3H), 2.10(q,1H), 2.07(s,3H), 1.70(m,2H), 1.60(m,2H), 1.40(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 162.1, 160.6, 144.4, 93.8, 91.7, 90 .4, 93.8, 59.6, 55.8, 53.7, 53.5, 47.0, 37.9, 36.2, 23.9, 19.2, 18.7; Molecular weight: 510.4.

[0091] Compound-A59: 4-(4-(7-chloro-2-(difluoromethyl)-4a,5,6,7,8,8a-hexahydroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:6.50(t,1H), 5.82(d,2H), 5.74(d,2H), 5.73(d,1H), 4.96(m,1H), 4.49(d,1H), 4.00(s,1H), 3 .83(s,6H), 3.65(t,4H), 3.42(m,3H), 2.78(t,4H), 2.33(s,3H), 2.10(q,1H), 1.70(m,2H), 1.60(m,2H), 1.40(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 164.6, 162.1, 160.6, 144.4, 122.4 , 95.5, 93.8, 91.7, 59.6, 55.8, 53.0, 38.2, 37.5, 36.5, 23.9, 19.2; Molecular weight: 531.21.

[0092] Compound-A60: 4-(4-(7-chlorodecahydroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:5.82(s,1H), 5.74(d,2H), 5.73(d,1H), 4.00(s,1H), 3.83(s,6H), 3.42(m,1H), 2.84(s,8H), 2.79(m, 2H), 2.62(q,1H), 2.56(q,1H), 2.33(s,3H), 2.00(t,1H), 1.89(d,2H), 1.70(m,2H), 1.65(m,2H), 1.49(m,2H), 1.32(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 164.6, 160.6, 144.4, 93.8, 90.4, 68.7, 55.8, 54.1, 53.1, 48.7, 48.2, 41.8, 32.0, 28.8, 24.7, 18.9; Molecular weight: 500.27.

[0093] Compound A61: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxycyclohex-1-en-1-yl)-6-methylpyrimidin-2-amine; 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.70(dd,1H), 7.70(dd,1H), 7.13(d,1H), 6.44(d,1H), 5.06(d,1H), 5.82(d,1H), 4.00(s,1H), 3.90(s,8H), 3.31(d,1H), 3.30(d,1H), 3.30(s,6H), 2.33(s,3H), 2.00(m,2H), 2.11(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 164.6, 160.6, 144.4, 93.8, 90.4, 68.7, 55.8, 54.1, 53.1, 48.7, 48.2, 41.8, 32.0, 28.8, 24.7, 18.9; Molecular weight: 500.27.

[0094] Compound-A62: 5-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)cyclohexane-1,3-diol: 1H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(s,1H), 7.36(dd,1H), 7.13(d,1H), 6.44(d,1H), 5.82(d,1H), 4 .00(s,1H), 3.90(s,8H), 3.31(d,1H), 3.30(d,1H), 2.33(s,3H), 2.57(d,1H), 1.72(m,2H), 1.74(m,2H), 1.68(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 164.5, 160.6, 159.2, 135.6, 130.6, 128.6, 126.0, 122.2, 118.6, 9 3.8, 61.7, 49.8, 45.5, 55.8, 54.1, 53.1, 48.7, 48.2, 40.2, 32.0, 28.8, 24.7, 23.9; Molecular weight: 468.20.

[0095] Compound-A63: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethylcyclohexyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(dd,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d,1H), 4.00(s,1H), 3 .90(s,8H), 3.31(d,1H), 3.30(d,1H), 2.33(s,3H), 2.57(d,1H), 1.72(m,2H), 1.74(m,2H), 1.68(m,2H), 0.96(s,6H); 13 C-NMR-400-MHz-DMSO:170.2, 164.5, 160.6, 159.2, 153.0, 150.8, 128.6, 1 26.0, 122.6, 118.6, 93.8, 48.5, 44.0, 43.4, 28.1, 23.9, 21.0; Molecular weight: 464.28.

[0096] Compound-A64: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methyl-N-(3-methylenecyclohexyl)pyrimidin-2-amine: 1H-NMR-400MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.30(d,1H), 6.44(d,1H), 5.82(d,1H), 5.11(s, 8H), 4.00(s,1H), 3.90(s,8H), 2.65(m,1H), 2.33(s,3H), 2.02(d,1H), 1.95(m,2H), 1.45(m,2H), 1.34(m,2H); 13 C-NMR-400MHz-DMSO:170.2, 164.5, 160.6, 159.2, 153.0, 150.8, 148.9, 135.6, 130.0, 128. 6, 126.0, 122.6, 118.3, 107.8, 93.8, 69.9, 49.8, 48.5, 42.5, 35.7, 31.4, 23.9; Molecular weight: 448.21.

[0097] Compound-A65: 3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)cyclohexanone: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d,1H), 4.00(s, 1H), 3.90(s,8H), 2.95(m,1H), 2.33(s,3H), 2.20(m,2H), 2.10(m,2H), 2.00(m,2H), 2.08(m,2H), 1.79(m,2H); 13 C-NMR-400-MHz-DMSO:210.8, 170.2, 164.5, 160.6, 159.2, 153.0, 150.8, 148.9, 135.6, 130.0, 1 28.6, 126.0, 122.6, 118.3, 107.8, 93.8, 69.9, 49.8, 48.5, 42.5, 35.7, 31.4, 23.9; Molecular weight: 450.19.

[0098] Compound-A66: 2-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)cyclohexa-2,5-diene-1,4-dione: 1H-NMR-400-MHz-DMSO:8.01(d,1H), 7.62(d,1H), 7.57(s,1H), 7.38(d,1H), 7.32(d, 2H), 6.87(s,2H), 6.25(s,1H), 5.82(s,1H), 4.00(s,1H), 3.90(s,8H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:185.7, 181.7, 170.2, 164.5, 160.6, 159.2, 153.0, 153.3, 150.8, 148.9, 136.8, 1 35.6, 136.8, 128.0, 122.6, 118.3, 107.8, 93.8, 69.9, 49.8, 48.5, 42.5, 35.7, 31.4, 23.9; Molecular weight: 460.16.

[0099] Compound-A67: 4-(4-(7-chloro-2-methylquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-40MHz-DMSO:8.24(d,1H), 7.84(s,1H), 7.32(d,1H), 6.66(d,1H), 5.82(d,2H), 5. 74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.83(s,6H), 3.90(s,8H), 2.33(s,3H), 2.53(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 164.1, 160.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128. 4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0; Molecular weight: 504.20.

[0100] Compound-A68: 4-(4-(7-chloro-2,8-dimethylquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:7.86(d,1H), 7.58(s,1H), 7.15(s,1H), 6.38(s,1H), 5.82(d,1H), 5.74(s, 2H), 5.73(s,1H), 4.00(s,1H), 3.28(s,8H), 3.83(s,6H), 2.64(s,3H), 2.45(s,3H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 518.44.

[0101] Compound-A69: 4-(4-(7-chloro-2,3-dimethylquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:7.86(d,1H), 7.58(s,1H), 7.15(s,1H), 6.38(s,1H), 5.82(d,1H), 5.74(s, 2H), 5.73(s,1H), 4.00(s,1H), 3.90(s,8H), 3.83(s,6H), 2.45(s,3H), 2.23(s,3H), 2.31(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 504.20.

[0102] Compound-A70: 4-(4-(7-chloroquinolin-4-yl)-2,6-dimethylpiperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.01(d,1H), 7.62(d,1H), 7.57(s,1H), 7.38(d,1H), 7.32(d,2H), 6.98(d,2H), 5.74(d, 2H), 5.73(d,1H), 5.82(d,1H), 4.00(s,1H), 3.38(s,4H), 3.03(m,2H), 3.83(s,6H), 2.33(s,3H), 1.12(s,6H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 518.22.

[0103] Compound-A71: 4-(7-(7-chloroquinolin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.01(d,1H), 7.62(d,1H), 7.57(s,1H), 7.38(d,1H), 7.32(d,2H), 6.98(d,2H), 5 .74(d,2H), 5.73(d,1H), 5.82(d,1H), 4.00(s,1H), 3.38(s,6H), 3.83(s,6H), 2.33(s,3H), 0.35(m,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 516.02.

[0104] Compound-A72: 4-(4-(7-chloro-2-methylquinolin-4-yl)-2-methylpiperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.02(d,1H), 7.59(dd,1H), 7.48(d,1H), 7.28(d,1H), 6.41(s,1H), 5.74(d,2H), 5 .73(d,1H), 5.82(d,1H), 4.00(s,1H), 3.83(s,6H), 3.38(m,2H), 3.01(m,6H), 3.03(d,1H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 518.22.

[0105] Compound-A73: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxy-4-methylphenyl)-5,6-dimethylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.01(d,1H), 7.62(d,1H), 7.57(s,1H), 7.38(d,1H), 7.32(d, 2H), 6.98(d,2H), 5.62(d,2H), 4.00(s,1H), 3.83(s,6H), 3.38(m,8H), 2.33(s,6H); 13 C-NMR-400-MHz-DMSO:170.4, 165.0, 164.5, 160.4, 159.2, 153.0, 149.2, 141.4, 135.4, 129.5, 128.4, 1 24.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6, 18.8, 15.9, 9.5; Molecular weight: 518.22.

[0106] Compound-A74: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethylphenyl)-5,6-dimethylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.01(d,1H), 7.62(d,1H), 7.57(s,1H), 7.38(d,1H), 7.32(d, 2H), 6.98(d,2H), 5.62(d,2H), 4.00(s,1H), 3.38(m,8H), 2.34(s,6H), 2.33(s,6H); 13 C-NMR-400-MHz-DMSO:170.2, 165.4, 159.2, 163.0, 150.8, 142.2, 139.1, 135.6, 130.1, 128. 9, 126.0, 122.6, 120.6, 118.6, 118.0, 98.9, 91.7, 49.8, 48.5, 21.6, 18.0, 15.9; Molecular weight: 472.11.

[0107] Compound A75: 4-(4-(7-chloro-2-methylquinolin-4-yl)-3-methylpiperazin-1-yl)-N-(3,5-dimethylphenyl)-5,6-dimethylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.02(d,1H), 7.59(d,2H), 7.48(dd,1H), 7.28(d,1H), 6.71(d,1H), 6.41(d ,2H), 4.00(s,1H), 3.38(m,6H), 3.03(d,1H), 2.34(s,6H), 2.33(s,6H), 2.45(s,6H), 1.22(s,3H); 13 C-NMR-400-MHz-DMSO:170.4, 165.7, 165.4, 160.5, 158.4, 149.4, 142.4, 139.1, 129.5, 128.4, 124.0 ,121.5,118.0,118.8,98.6,91.7,90.4,65.8,52.8,49.1,48.5,21.6,20.0,18.0,16.3;Molecular weight:500.25.

[0108] Compound-A76: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3-ethoxy-5-methoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.02(d,1H), 7.62(d,2H), 7.57(dd,1H), 7.38(d,1H), 7.32(d,1H), 6.98(d,1H), 6.37(s,1H), 5 .74(s,2H), 5.73(s,1H), 5.82(d,1H), 4.09(q,2H), 4.00(s,1H), 3.38(s,8H), 3.83(d,3H), 2.33(s,6H), 1.32(s, 3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.2, 159.2, 153.0, 150.8, 144.0, 135.6, 130.1, 128.9, 126.0, 126.3, 118.3, 93.8, 91.8, 91.0, 64.6, 55.8, 49.5, 48.5, 23.9, 14.8; Molecular weight: 504.20.

[0109] Compound-A77: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-diethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.02(d,1H), 7.62(d,2H), 7.57(dd,1H), 7.38(d,1H), 7.32(d,1H), 6.98(d,1H), 6.37(s,1H), 5 .74(s,2H), 5.73(s,1H), 5.82(d,1H), 4.09(q,4H), 4.00(s,1H), 3.38(s,8H), 3.83(d,3H), 2.33(s,6H), 1.32(s,6H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 159.2, 158.8, 153.0, 150.8, 143.4, 13 5.6, 130.1, 128.9, 126.0, 122.6, 118.3, 93.8, 91.1, 64.6, 49.8, 48.5, 14.8; Molecular weight: 518.22.

[0110] Compound-A78: 4-(4-(2,7-dichloro-3-methoxyquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400MHz-DMSO:8.16(d,1H), 7.84(d,1H), 7.36(m,1H), 5.82(d,1H), 5.74(s, 2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,9H), 2.53(s,3H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 159.2, 158.8, 153.0, 150.8, 143.4, 13 5.6, 130.1, 128.9, 126.0, 122.6, 118.3, 93.8, 91.1, 64.6, 49.8, 48.5, 14.8; Molecular weight: 554.16.

[0111] Compound-A79: 4-(4-(7-chloro-6-methoxyquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.25(d,1H), 7.80(s,1H), 7.10(s,1H), 6.44(d,1H), 5.82(d,1H), 5.74(s, 2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,9H), 2.53(s,3H), 2.53(s,3H), 2.31(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 158.6, 150.6, 146.5, 144.4, 131.6, 126. 6, 128.9, 126.0, 122.6, 118.3, 104.1, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 14.8; Molecular weight: 520.20.

[0112] Compound-A80: 4-(4-(7-chloro-8-methoxyquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:7.86(d,1H), 7.50(d,1H), 6.70(s,1H), 5.82(d,1H), 5.74(s,2H), 5 .73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,9H), 2.53(s,3H), 2.53(s,3H), 2.31(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 520.20.

[0113] Compound-A81: N-(3,5-dimethoxyphenyl)-4-(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 7.98(d,1H), 7.27(d,1H), 7.24(d,1H), 6.33(d,1H), 5 .82(d,1H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,9H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 486.24.

[0114] Compound-A82: N-(3,5-dimethoxyphenyl)-4-(4-(6,7-dimethoxyquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-amine: 1H-NMR-400MHz-DMSO:8.25(d,1H), 7.20(s,1H), 7.09(d,1H), 6.33(d,1H), 5.82(d,1) H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,12H), 2.33(s,3H); 13 C-NMR-400MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 516.25.

[0115] Compound-A83: N-(3,5-dimethoxyphenyl)-4-methyl-6-(4-(5,6,7-trimethoxyquinolin-4-yl)piperazin-1-yl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.29(d,1H), 6.82(s,1H), 6.36(dd,1H), 5.82(d,1H), 5 .74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,16H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 160.6, 157.6, 158.2, 150.5, 146.3, 144.4, 128.4, 115.0, 114.6, 99.7, 93.8, 91.7, 60.7, 56.1, 55.8, 49.8, 48.5, 23.9; Molecular weight: 546.26.

[0116] Compound-A84: 4-(4-(6,7-diethoxy-5-methoxyquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.29(d,1H), 6.82(s,1H), 6.36(dd,1H), 5.82(d,1H), 5.74(s ,2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,9H), 2.33(s,3H), 1.33(s,6H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 160.6, 156.8, 158.2, 150.5, 158.4, 146.3, 144.4, 135 .4, 129.5, 128.4, 124.0, 121.1, 115.5, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 14.8; Molecular weight: 574.29

[0117] Compound-A85: N-(3,5-diethoxyphenyl)-4-(4-(6,7-diethoxyquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.25(d,1H), 7.20(s,1H), 7.09(s,1H), 6.33(d,1H), 5.82(d,1H), 5. 74(s,2H), 5.73(s,1H), 4.09(m,8H), 4.00(s,1H), 3.38(s,8H), 2.33(s,3H), 1.33(s,12H); 13 C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 158.5, 157.9, 153.4, 150.2, 145.5, 124. 5, 116.7, 107.6, 104.7, 93.8, 91.1, 90.6, 64.6, 49.8, 48.5, 23.9, 14.8; Molecular weight: 572.31.

[0118] Compound-A86: N-(3,5-dimethoxyphenyl)-4-(4-(6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.49(d,1H), 7.41(s,1H), 7.24(s,1H), 5.82(d,1H), 5 .74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,9H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:178.1, 170.2, 168.1, 164.5, 160.6, 159.2, 154.7, 152.3, 148 .1, 119.2, 108.2, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 517.24.

[0119] Compound-A87: 4-(4-(7-chloro-1,8-naphthyridin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.68(d,1H), 8.55(d,1H), 7.77(d,1H), 6.71(d,1H), 5.82(d, 1H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,6H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 156.6, 153.2, 148.1, 144.4, 1 37.3, 122.4, 120.4, 109.0, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 491.24.

[0120] Compound-A88: 4-(4-(7-chloro-1,5-naphthyridin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.19(d,1H), 8.95(dd,1H), 8.65(d,1H), 6.86(d,1H), 5.82(d ,1H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.38(s,8H), 3.83(s,6H), 2.33(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.0, 164.5, 160.6, 155.3, 150.2, 148.2, 144.4, 1 35.5, 127.6, 124.3, 109.3, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9; Molecular weight: 491.18

[0121] Compound-A89: 4-(3-(7-chloroquinolin-4-yl)imidazolidin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.37(d,2H), 7.87(d,2H), 6.44(d,1H), 5.82(d, 1H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 4.83(s,2H), 3.29(s,4H), 3.83(s,6H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:167.0, 168.1, 160.6, 159.2, 153.0, 150.8, 149.2, 144.4, 1 30.1, 126.0, 122.6, 118.0, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6. Molecular weight: 476.17.

[0122] Compound-A90: 4-(3-(7-chloroquinazolin-4-yl)imidazolidin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.49(s,1H), 8.02(d,1H), 7.87(d,1H), 7.78(d,1H), 6.44(d,2H), 5.82(d, 1H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 4.83(s,2H), 3.29(s,4H), 3.83(s,6H), 2.33(s,3H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 477.17.

[0123] Compound-A91: 4-(3-(7-chloro-1,8-naphthyridin-4-yl)imidazolidin-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.68(s,1H), 8.55(d,1H), 7.77(d,1H), 6.71(d,1H), 5.82(d,1H), 5 .74(s,2H), 5.73(s,1H), 4.00(s,1H), 4.83(s,2H), 3.29(s,4H), 3.83(s,6H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 477.17.

[0124] Compound-A92: 4-(4-(7-chloroquinolin-4-yl)-1,4-diazepan-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d,1H), 5 .74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.68(t,4H), 3.29(s,4H), 3.83(s,6H), 2.33(s,3H), 1.75(m,2H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 504.20.

[0125] Compound A93: 4-(4-(7-chloroquinazolin-4-yl)-1,4-diazepan-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.49(s,1H), 8.02(s,1H), 7.87(d,1H), 7.78(d,1H), 6.44(d,1H), 5.82(d,1H), 5 .74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.68(t,4H), 3.29(s,4H), 3.83(s,6H), 2.33(s,3H), 1.75(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 504.20.

[0126] Compound A94: 4-(4-(7-chloro-1,8-naphthyridin-4-yl)-1,4-diazepan-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine 1 H-NMR-400-MHz-DMSO:8.68(d,1H), 8.55(d,1H), 7.77(d,1H), 6.71(d,1H), 5.82(d,1H), 5.74(s, 2H), 5.73(s,1H), 4.00(s,1H), 4.83(s,2H), 3.29(s,4H), 3.83(s,6H), 2.33(s,3H), 1.75(m,2H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 504.20.

[0127] Compound-A95: 4-(4-(7-chloro-1,5-naphthyridin-4-yl)-1,4-diazepan-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.19(s,1H), 8.95(d,1H), 8.65(d,1H), 6.86(d,1H), 5.82(d,1H), 5.74(s, 2H), 5.73(s,1H), 4.00(s,1H), 3.68(t,4H), 3.29(s,4H), 3.83(s,6H), 2.33(s,3H), 1.75(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 505.20.

[0128] Compound A96: 4-(4-(7-chloro-1,5-naphthyridin-4-yl)-1,4-diazepan-1-yl)-N-(3,5-dimethoxyphenyl)-6-(trifluoromethyl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.19(s,1H), 8.95(d,1H), 8.65(s,1H), 6.84(d,1H), 5.82(d,1H), 5 .74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.68(t,4H), 3.29(s,4H), 3.83(s,6H), 1.75(m,2H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 559.19.

[0129] Compound-A97: 4-(4-(7-chloro-4a,5,6,7,8,8a-hexahydroquinolin-4-yl)piperazin-1-yl)-N-(3-ethoxy-5-methoxyphenyl)-6-fluoropyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:7.50(d,1H), 5.26(d,1H), 5.74(d,2H), 5.73(d,1H), 4.96(m,1H), 4.49(d,1H), 4.09(m,1H), 4.00(s,1H), 3. 83(s,3H), 3.65(t,4H), 3.42(m,3H), 2.78(t,4H), 2.33(s,3H), 2.10(q,1H), 1.70(m,2H), 1.60(m,2H), 1.40(m,2H)1.3233(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 514.23.

[0130] Compound-A98: 4-(7-(7-chloroquinolin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3,5-dimethoxycyclohex-1-en-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine: 1H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5.74(d,2H), 5.73(d,1H), 5.82(d,1H), 4.00(s, 1H), 3.30(s,6H), 3.28(s,4H), 3.21(s,4H), 3.31(m,1H), 3.00(m,4H), 2.10(m,2H), 2.00(m,2H), 2.33(s,3H), 1.12(s,3H), 0.35(m,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 514.23.

[0131] Compound-A99: 4-(4-(2,7-dichloro-3-methoxyquinolin-4-yl)piperazin-1-yl)-N-(2,6-difluoro-3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.16(d,1H), 7.84(s,1H), 7.36(d,1H), 7.36(d,1H), 5.90(t, 1H), 5.82(s,1H), 5.98(d,1H), 4.00(s,1H), 3.30(s,8H), 3.83(s,9H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 590.14.

[0132] Compound-A100: 2-((4-(4-(7-chloro-6-methoxyquinolin-4-yl)-2-methylpiperazin-1-yl)-5,6-dimethylpyrimidin-2-yl)amino)cyclohexa-2,5-diene-1,4-dione: 1 H-NMR-400-MHz-DMSO:8.25(d,1H), 7.80(s,1H), 7.10(s,1H), 6.87(s,2H), 6.44(d,1H), 6.25(s,1H), 5.82(d,1H), 4.00(s, 1H), 3.90(s,8H), 3.83(s,3H), 3.22(m,2H), 3.00(d,1H), 3.01(m,2H), 2.90(m,2H), 2.33(s,3H), 2.34(s,3H), 1.12(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 518.18.

[0133] Compound-A101: N-(3,5-diethoxyphenyl)-4-(3-(6,7-dimethoxyquinazolin-4-yl)imidazolidin-1-yl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.49(s,1H), 7.41(s,1H), 7.24(s,2H), 5.74(s,2H), 5.73(s,1H), 5.82(d, 1H), 4.83(s,2H), 4.09(q,4H), 4.00(s,1H), 3.29(s,4H), 3.83(d,3H), 2.33(s,6H), 1.32(s,6H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 531.26.

[0134] Compound-A102: 3-(7-chloro-1,8-naphthyridin-4-yl)-2-cyclopropyl-1-(2-((3,5-dihydroxycyclohexyl)amino)-6-methylpyrimidin-4-yl)imidazolidin-4-one: 1 H-NMR-400-MHz-DMSO:8.68(d,1H), 8.65(d,1H), 7.77(dd,1H), 7.76(d,1H), 5.82(d,1H), 4.71(d,1H), 3.95(d,2H), 4.00(s,1H), 3.90(s ,8H), 3.31(d,1H), 3.58(s,2H), 3.17(m,2H), 2.57(m,1H), 2.46(m,1H), 2.33(s,3H), 1.46(m,4H), 1.68(m,4H), 1.07(m,1H), 0.30(m,4H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 509.19.

[0135] Compound-A103: 4-(3-(7-chloro-8-methoxyquinolin-4-yl)imidazolidin-1-yl)-N-(3-fluoro-5-methoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.39(s,1H), 7.85(d,1H), 7.54(d,2H), 7.32(dd,1H), 6.50(d,2H), 6.48(d ,2H), 5.95(d,1H), 5.82(d,1H), 4.83(s,2H), 4.00(s,1H), 3.29(s,4H), 3.83(d,9H), 2.33(s,6H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 494.16.

[0136] Compound-A104: N-(3,5-dimethoxyphenyl)-4,5-dimethyl-6-(4-(5,6,7-trimethoxyquinazolin-4-yl)-1,4-diazepan-1-yl)pyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:8.49(s,1H), 6.97(s,1H), 5.74(s,2H), 5.73(s,1H), 4. 00(s,1H), 3.68(t,4H), 3.29(s,4H), 3.83(s,16H), 2.33(s,3H), 1.75(m,2H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 575.29.

[0137] Compound-A105: 4-(4-(7-chloro-2-(thiophen-2-yl)-1,5-naphthyridin-4-yl)-1,4-diazepan-1-yl)-N-(3,5-dimethoxyphenyl)-6-methylpyrimidin-2-amine: 1 H-NMR-400-MHz-DMSO:9.19(s,1H), 8.65(s,1H), 7.85(d,1H), 7.69(d,1H), 7.17(d,1H), 5.82(d, 1H), 5.74(s,2H), 5.73(s,1H), 4.00(s,1H), 3.68(t,4H), 3.29(s,4H), 3.83(s,6H), 1.75(m,2H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 587.19.

[0138] Compound-A106: 3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)-5-methoxyphenol: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d, 1H), 5.90(d,1H), 5.74(d,1H), 5.35(s,1H), 3.83(s,3H), 4.00(s,1H), 3.28(s,8H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 476.17.

[0139] Compound-A107: 3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)amino)-5-methoxyphenol: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 5.90(d,1H), 5.74(d,1H), 5.35(s,1H), 3.83(s,3H), 4.00(s,1H), 3.28(s,8H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 530.17.

[0140] Compound-A108: 5-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)benzene-1,3-diol: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5 .82(d,1H), 5.90(d,1H), 5.74(d,1H), 5.35(s,2H), 4.00(s,1H), 3.28(s,8H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 462.16.

[0141] Compound-A109: 5-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)amino)benzene-1,3-diol: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d, 1H), 5.82(d,1H), 5.90(d,1H), 5.74(d,1H), 5.35(s,2H), 4.00(s,1H), 3.28(s,8H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 516.17.

[0142] Compound-A110: N1-(4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)-5-methoxy-N3,N3-dimethylbenzene-1,3-diamine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d, 1H), 5.52(d,1H), 5.46(d,1H), 5.67(s,1H), 3.83(s,3H), 3.06(s,6H), 4.00(s,1H), 3.28(s,8H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 503.22.

[0143] Compound-A111: N1-(4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)-5-methoxybenzene-1,3-diamine: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 6.27(s,2H), 5 .82(d,1H), 5.52(d,1H), 5.46(d,1H), 5.67(s,1H), 3.83(s,3H), 3.06(s,6H), 4.00(s,1H), 3.28(s,8H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 475.19.

[0144] Compound-A112: 3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)-5-methoxybenzonitrile: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 6.27(s,2H), 5. 82(d,1H), 6.97(t,1H), 6.46(dd,1H), 6.28(t,1H), 3.83(s,3H), 4.00(s,1H), 3.28(s,8H), 2.33(s,3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 475.19.

[0145] Compound-A113: 3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)amino)-5-methoxybenzonitrile: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 6.27(s, 2H), 5.82(d,1H), 6.97(t,1H), 6.46(dd,1H), 6.28(t,1H), 3.83(s,3H), 4.00(s,1H), 3.28(s,8H); 13C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 539.14.

[0146] Compound-A114: 3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)amino)-5-hydroxybenzonitrile: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 6.27(s, 2H), 5.82(d,1H), 5.35(s,1H), 6.93(t,1H), 6.42(dd,1H), 6.28(t,1H), 4.00(s,1H), 3.28(s,8H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 525.13.

[0147] Compound-A115: 1-(3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)-5-methoxyphenyl)ethanone: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d,1H), 6 .85(t,1H), 6.37(t,1H), 6.56(d,1H), 3.83(s,3H), 4.00(s,1H), 3.28(s,8H), 2.50(s,3H), 2.33(s,3H); 13C-NMR-400-MHzDMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 1 28.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 502.13.

[0148] Compound-A116: 1-(3-((4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-yl)amino)-5-methoxyphenyl)ethanol: 1 H-NMR-400-MHz-DMSO:8.36(d,1H), 8.23(d,1H), 7.87(d,1H), 7.36(d,1H), 6.44(d,1H), 5.82(d,1H), 6.50(d,1H), 6 .24(s,1H), 6.11(d,1H), 3.65(s,1H), 3.83(s,3H), 4.68(t,1H), 4.00(s,1H), 3.28(s,8H), 2.33(s, 3H)1.49(d, 3H); 13 C-NMR-400-MHz-DMSO:170.2, 168.1, 164.5, 160.6, 157.6, 158.2, 149.2, 144.4, 135.4, 129.5, 128.4, 124.0, 121.1, 111.8, 93.8, 91.7, 90.4, 55.8, 49.8, 48.5, 23.9, 20.0, 16.6; Molecular weight: 502.13.

[0149] Example 2 Experiments to test the anticancer properties of compounds A1-A116 Cells used to test the anti-cancer properties of compounds The following human-derived non-small cell lung cancer cell lines were used to test the efficiency of compounds to induce cell death and to evaluate the anti-cancer properties of the compounds: 1. A549 cells: Adenocarcinoma human alveolar basal epithelial cells. These cells are used as a model for studying lung cancer and developing drug therapies for it. 2. NCI-H-460 cells are also human lung cancer cells. 3. NCI-H-522 cells are also human lung cancer cells.

[0150] Cytotoxicity Assay Protocol 500 cells / well / 30μL were seeded into 384-well cell culture plates and incubated overnight in a cell culture incubator at 37°C and 5% CO2. 10μL of 4X compound was added to the plate and incubated for 72 hours in a cell culture incubator at 37°C and 5% CO2. A DMSO control was included in the assay as a 0% cytotoxicity control. The assay was terminated by adding 10μL of CTG2.0 detection reagent #G9242. The plate was incubated at room temperature with shaking for 20 minutes and read on the Envision. Ultrasensitive luminescence and data were analyzed to determine the percent cytotoxicity of the compound relative to the DMSO control.

[0151] CellTiter-Glo Assay Protocol Cells were cultured and maintained in F12K + 10% FBS + 1x anti-antibody media or RPMI + 10% FBS + 1x anti-antibody media. Cells were trypsinized and expanded to ensure they were not overly confluent and in logarithmic growth phase. On day 0, 500 cells / well were seeded in 30 μL of media in a cell culture-treated white flat-bottom 384-well plate, centrifuged at 40 x g for 10 seconds, and incubated overnight at 37°C in a 5% CO2 incubator. On day 1, 4x compound concentrations were prepared in complete media, 10 μL was added to the cells, centrifuged at 40 x g for 10 seconds, and incubated at 37°C in a 5% CO2 incubator for 72 hours. Compounds tested: 100 μM top solution, 3x dilutions, 10-point DRCs in triplicate. The final DMSO concentration was maintained at 0.5% for all compounds. No compound / DMSO was used as a control. On day 4 (72 hours after treatment), the plates were returned to room temperature for 10 minutes, 10 μl of CellTiter-Glo reagent was added to each well, and the plates were placed on an orbital shaker at room temperature for 10 minutes. Luminescence signals were read on an Envision plate reader using the ultrasensitive luminescence protocol. Data were plotted and analyzed using the following formula: RLU of DMSO control-treated cells is considered to be 100% cell viability. Luminescence rate = ((Sample RLU) / (Average DMSO RLU)) x 100

[0152] Cancer cytotoxicity test results for derivatives of formula A All compounds A1 to A116 were tested for cytotoxicity using the non-small cell lung cancer cell line by the above method. Table 5 shows the cytotoxicity results of the derivative of formula A that showed the most effective toxicity against cancer cells among all the derivatives of formula A tested. Table 5: Cytotoxicity results of the most efficient derivatives of formula A [Table 5]

[0153] It is clear that compounds A1, A2, A4, A5, A6, A7, A8, A11, A12, A13, A16, A19, A20, A21, A22, A23, A24, A33, A36, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, and A49 are active against non-small cell lung cancer, whereas the other tested derivatives of Formula A exhibited less efficient cytotoxicity against non-small cell lung cancer cell lines. These selected derivatives of Formula A were further tested to confirm their efficacy as anticancer compounds.

[0154] CellTitre-Glo Assay Results for Selected Formula A Derivatives Compounds A1, A2, A4, A5, A6, A7, A8, A11, A12, A13, A16, A19, A20, A21, A22, A23, A24, A33, A36, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, and A49, which showed the greatest efficacy in cytotoxicity tests, were further tested using CellTitre-Glo. Of the selected compounds, A1, A7, A42, A43, A48, and A49 showed the highest efficacy in cytotoxicity against non-small cell lung cancer cell lines. Table 6 shows the IC50 values ​​for the most effective derivatives of Formula A. Table 6: CellTitre-Glo assay results for selected derivatives of Formula A [Table 6] Figures 1-3 show the cytotoxicity curves of compound A1 versus concentration in various cell lines.

[0155] References 1.Kamb, A., et. al., Why is cancer drug discovery so difficult? Nat. Rev. Drug Discov. 6, 115-20 (2007) 2. Chin, L. & Gray, J. W. Translating insights from the cancer genome into clinical practice. Nature 452, 553-563 (2008) 3.Moffat, J. G., et. al., Opportunities and challenges in phenotypic drug discovery: an industry perspective. Nature Reviews Drug Discovery 16, 531-543 (2017) 4.Moffat, J. G., et. al., Phenotypic screening in cancer drug discovery - past, present and future. Nature Reviews Drug Discovery 13, 588-602 (2014)

Claims

1. A compound of formula A, or a stereoisomer, tautomer, solvate, hydrate, or pharmaceutically acceptable salt thereof: 【Chemical 1】 In formula A, R １ is selected from the group consisting of: 【Chemistry 13】 【Chemistry 14】 R ２ is selected from the group consisting of: 【Chemistry 15】 R ３ is CF ３ , C.H. ３ , H and F; R ４ are H, F and CH ３ selected from the group consisting of: R ５ is H and CH ３ selected from the group consisting of: R ６ is H; R ７ is H and CH ３ selected from the group consisting of: R ８ is H and CH ３ wherein m=0 and n=0.

2. R １ teeth 【Chemistry 2】 R ２ teeth 【Chemistry 3】 R ３ is CF ３ , R ４ is H, R ５ is H, R ６ is H, R ７ is H, R ８ The compound of claim 1, wherein is H, m=0, n=0, and has the chemical structure represented by compound A1. 【Chemistry 4】 Compound A1: 4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(3,5-dimethoxyphenyl)-6-(trifluoromethyl)pyridin-2-amine.

3. R １ teeth 【Chemistry 5】 R ２ teeth, 【Chemistry 3】 R ３ is CF ３ , R ４ is H, R ５ is H, R ６ is H, R ７ is H, R ８ The compound of claim 1, wherein is H, m=0, n=0, and has the chemical structure represented by Compound A7. 【Chemistry 6】 Compound A7: {4-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)-N-(5-methoxypyridin-3-yl)-6-(trifluoromethyl)pyrimidin-2-amine}

4. R １ teeth, 【Chemistry 2】 R ２ teeth, 【Chemistry 7】 R ３ is CH ３ , R ４ is H, R ５ is H, R ６ is H, R ７ is H, R ８ The compound of claim 1, wherein is H, m=0, n=0, and has the chemical structure represented by compound A42. 【Chemistry 8】 Compound A42: N-(3,5-dimethoxyphenyl)-4-methyl-6-(4-(quinolin-4-yl)piperazin-1-yl)pyrimidin-2-amine.

5. R １ teeth, 【Chemistry 2】 R ２ teeth, 【Chemistry 7】 R ３ is CF ３ , R ４ is H, R ５ is H, R ６ is H, R ７ is H, R ８ The compound of claim 1, wherein is H, m=0, n=0, and has the chemical structure represented by compound A43. 【Chemistry 9】 Compound A43: N-(3,5-dimethoxyphenyl)-4-(4-(quinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine.

6. R １ teeth, 【Chemistry 2】 R ２ teeth 【Chemistry 10】 R ３ is CH ３ , R ４ is H, R ５ is H, R ６ is H, R ７ is H, R ８ The compound of claim 1, wherein is H, m=0, n=0, and has the chemical structure represented by compound A48. 【Chemistry 11】 Compound A48: N-(3,5-dimethoxyphenyl)-4-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)-6-methylpyrimidin-2-amine.

7. R １ teeth, 【Chemistry 2】 R ２ teeth, 【Chemistry 10】 R ３ is CF ３ , R ４ is H, R ５ is H, R ６ is H, R ７ is H, R ８ The compound of claim 1, wherein is H, m=0, n=0, and has the chemical structure represented by compound A49. 【Chemistry 12】 Compound A49: N-(3,5-dimethoxyphenyl)-4-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-amine.

8. A pharmaceutical composition comprising a compound according to any one of claims 1 to 7 and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle or a combination thereof.

9. 10. A method for treating a disease, comprising administering an effective amount of the composition of claim 9 to a person in need thereof, wherein the disease is cancer, including lung cancer.

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