Benzylamine formyl compound as well as preparation method and application thereof

Abstract

The invention discloses a benzylamine formyl compound as well as a preparation method and application thereof. Specifically, the invention provides benzylamine formyl compounds as shown in a general formula I and pharmaceutically acceptable salts thereof, and the benzylamine formyl compounds and the pharmaceutically acceptable salts thereof have excellent inhibitory activity on SOS1 protein and can be used for treating cancers. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemistry, and specifically relates to a substituted benzylamine formyl compound and a preparation method and application thereof. Background Art

[0002] SOS1 (Son of sevenless homologue 1) protein is a guanine nucleotide exchange factor (GEFs) that is widely expressed in humans and is associated with various human cancers and other diseases. In human cells, activated SOS1 can promote the conversion between inactive RAS-GDP and active RAS-GTP, while activated RAS (Rat Sarcoma Virus) can activate multiple downstream signals, such as RAF-MEK-ERK, PI3K-AKT-mTOR and Ral-GDS, to regulate cell survival and proliferation. Inhibition of SOS1 protein can inhibit the activation of RAS protein, thereby inhibiting the occurrence and development of tumors (such as lung cancer, uterine endometrial cancer, bladder cancer, ovarian cancer, intestinal cancer, liver cancer, leukemia, glioma and melanoma, etc.).

[0003] Research on SOS1 inhibitors is still in the early stages of development. Currently, only two drugs are in clinical trials, and no drug has been successfully marketed. Therefore, it is of great significance to develop new SOS1 small molecule inhibitors with good anti-tumor activity. Summary of the invention

[0004] The purpose of the present invention is to provide a series of benzylamine compounds for treating various related tumor diseases by inhibiting SOS1 protein and regulating RAS-MEK-ERK and other signal pathways.

[0005] The technical solution of the present invention is as follows:

[0006] A substituted benzylamine formyl compound and a pharmaceutically acceptable salt thereof as shown in general formula I, wherein the structure is as follows:

[0007]

[0008] Ring A is

[0009] R 1 It is an alkoxy group, morpholine, or an unsubstituted or halogen-substituted benzene ring.

[0010] The benzylamine formyl compound and its pharmaceutically acceptable salt are characterized in that the compound is any of the following compounds:

[0011]

[0012]

[0013] A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.

[0014] Use of the benzylamine formyl compound or its pharmaceutically acceptable salt and the pharmaceutical composition in the preparation of SOS1 inhibitor drugs.

[0015] Application of the benzylamine formyl compound or its pharmaceutically acceptable salt and the pharmaceutical composition in the preparation of anti-tumor drugs.

[0016] Beneficial Effects

[0017] Compared with the prior art, the present invention has the following significant features:

[0018] The present invention discloses a class of compounds with a completely new structure, which can effectively inhibit the SOS1 protein target and can be used to prepare drugs for treating cancer or tumor-related diseases; the present invention also discloses a method for preparing the compound of general formula I. DETAILED DESCRIPTION

[0019] In order to better understand the present invention, the present invention is further illustrated by the following examples, but the content of the present invention is not limited to the following examples.

[0020] Example 1

[0021]

[0022] Synthesis route:

[0023]

[0024] Synthesis of compound I-1c

[0025] 5-Methoxynicotinic acid I-1a (100 mg, 0.65 mmol), (R)-1-[3-nitro-5-(trifluoromethyl)phenyl]ethylamine I-1b (193 mg, 0.72 mmol, 1.1 eq), HATU (371 mg, 0.98 mmol, 1.5 eq), DIPEA (454 μL, 2.6 mmol, 4 eq) were dissolved in 3 mL of DMF. The reaction solution was stirred at room temperature for 6 hours, water was added, and extracted with ethyl acetate. The combined organic phase was washed with water, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain compound I-1c (207 mg, yield 86%).

[0026] Synthesis of Compound I-1

[0027] Compound I-1c (170 mg, 0.46 mmol), zinc powder (299 mg, 4.6 mmol, 10 eq), and ammonium chloride (246 mg, 4.6 mmol, 10 eq) were dissolved in a mixed solvent of 2 mL of anhydrous ethanol and 0.4 mL of water. The reaction solution was refluxed for 24 h, cooled, and filtered. The filter cake was slurried with 1 mL of anhydrous ethanol to obtain solid I-1 (100 mg, yield 64%). 1 H NMR (300 MHz, DMSO-d 6 )δ9.00(d,J=2.9Hz,1H),8.66(d,J=1.8Hz,1H),8.43(d,J=2.9Hz,1H),7.76(dd,J=2.9,1.81Hz,1H),6.81–6. 80(brs,2H),6.72–6.71(brs,1H),5.59(s,2H),5.09(dq,J=7.6,7.0Hz,1H),3.89(s,3H),1.46(d,J=7.0,3H).

[0028] Example 2

[0029]

[0030] Synthesis route:

[0031]

[0032] Synthesis of compound I-2c

[0033] In N 2 Under protection, compound 3-bromopicolinic acid methyl ester 1-2a (216.0 mg, 1.00 mmol, 1.0 eq), phenylboronic acid 1-2b (134.0 mg, 1.1 mmol, 1.0 eq), tetrakistriphenylphosphine palladium (34.0 mg, 3 mol%) and sodium carbonate (212.0 mg, 2.0 mmol, 2.0 eq) were dissolved in a mixed solvent of 1 mL of water, 0.4 mL of methanol and 1.6 mL of toluene. The reaction solution was stirred at 80 ° C for 2 h, diluted with water, and extracted with ethyl acetate. The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain compound I-2c (140 mg, yield 66%).

[0034] Synthesis of compound I-2d

[0035] Compound I-2c (120 mg, 0.51 mmol) and lithium hydroxide (48 mg, 2 mmol, 4 eq) were dissolved in 1 mL of water and 2 mL of THF. The reaction solution was stirred at room temperature for 2 hours, and the pH was adjusted to 6-7 with dilute hydrochloric acid. The precipitated solid was filtered to obtain a white solid I-2d (110 mg, yield 97%).

[0036] Synthesis of compound I-2e

[0037] The specific synthesis steps refer to the synthesis of compound I-1c, and compound I-1a is replaced by compound I-2d to obtain compound I-2e.

[0038] Synthesis of Compound I-2

[0039] The specific synthesis steps refer to the synthesis of compound I-1, and compound I-1c is replaced by compound I-2e to obtain compound I-2 (59 mg, yield 64%) as a white solid. 1 H NMR (300 MHz, CDCl 3 )δ8.93(brs,2H),8.29(s,1H),7.59–7.55(m,2H),7.51–7.47(m,3H),6.99(s,1H),6.86(s,1H),6.80( s, 1H), 6.67 (d, J = 7.6Hz, 1H), 5.29 (dq, J = 7.6, 6.8Hz, 1H), 3.57-3.10 (brs, 2H), 1.61 (d, J = 6.8Hz, 3H).

[0040] Example 3

[0041]

[0042] Referring to the synthetic route of compound I-2, phenylboronic acid was replaced with p-fluorophenylboronic acid to obtain compound I-3 (62 mg, yield 69%) as a white solid. 1 H NMR (300 MHz, CDCl 3 )δ8.91(s,1H),8.81(s,1H),8.22(s,1H),7.50–7.44(m,2H),7.23–7.10(m,3H),6.97(s, 1H), 6.83 (s, 1H), 6.76 (s, 1H), 5.25 (m, 1H), 3.71–3.57 (brs, 2H), 1.57 (d, J = 6.6Hz, 3H).

[0043] Example 4

[0044]

[0045] Synthesis route:

[0046]

[0047] Synthesis of compound I-4c

[0048] 2-Chloroisonicotinic acid 1-4a (100 mg, 0.5 mmol), (R)-1-[3-amino-5-(trifluoromethyl)phenyl]ethylamine 1-4b (165 mg, 0.6 mmol, 1.2 eq), HATU (247 mg, 0.65 mmol, 1.3 eq), DIPEA (350 μL, 2.0 mmol, 4 eq) were dissolved in 1 mL of THF. The reaction solution was stirred at room temperature overnight and concentrated. The crude product was purified by column chromatography to obtain compound I-4c (161 mg, yield 80%).

[0049] Synthesis of Compound I-4

[0050] In N 2 Under protection, I-4c (120 mg, 0.31 mmol), p-fluorophenyl borate I-4d (82.6 mg, 0.37 mmol, 1.2 eq), tetrakistriphenylphosphine palladium (35.8 mg, 10 mol%), potassium carbonate (128.5 mg, 0.93 mmol, 3 eq) were dissolved in 1 mL of dioxane and 0.2 mL of water. The reaction solution was stirred at 90 ° C overnight, diluted with water, and extracted with ethyl acetate. The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain a white solid I-4 (21.2 mg, yield 17%). 1 H NMR (300 MHz, CDCl 3 )δ8.77(d,J=5.1Hz,1H),8.04-8.00(m,3H),7.46(dd,J=5.1,1.6Hz,1H),7.17(m,2H),6.98(s,1H),6.8 5(s,1H),6.82(s,1H),6.44(d,J=7.4Hz,1H),5.29(m,1H),3.95-3.87(brs,2H),1.60(d,J=4.3Hz,3H).

[0051] Example 5

[0052]

[0053] Synthetic route

[0054]

[0055] Synthesis of I-5

[0056] In N 2Under protection, I-4c (133 mg, 0.39 mmol, 1 eq), morpholine (70 μL, 0.78 mmol, 2 eq), palladium acetate (2.6 mg, 3 mol%), RuPhos (10.9 mg, 6 mol%), BrettPhos (13.2 mg, 6 mol%), sodium tert-butoxide (75 mg, 0.78 mmol, 2 eq) were dissolved in 1 mL of dioxane. The reaction solution was stirred at 100 ° C overnight, diluted with water, and extracted with ethyl acetate. The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain a white solid I-5 (50 mg, yield 33%). 1 H NMR (300 MHz, CDCl 3 )δ8.24(d,J=5.1Hz,1H),7.04(s,1H),6.95(s,1H),6.82(d,J=1.3Hz,1H),6.80(s,2H),6.50(d,J=7.8Hz,1H), 5.23(dq,J=7.8,7.0Hz,1H),4.01–3.87(brs,2H),3.81–3.78(m,4H),3.55–3.52(m,4H),1.56(d,J=7.0Hz,3H).

[0057] Example 6

[0058]

[0059] Referring to the synthesis method of compound I-4, 2-chloroisonicotinic acid was replaced with 5-amino-2-bromo-4-pyridinecarboxylic acid to obtain compound I-6 (27 mg, yield 21%). 1 H NMR (300 MHz, CDCl 3 )δ8.41(s,1H),7.76(d,J=2.1Hz,1H),7.52–7.42(m,4H),7.39–7.31(m,1H),6.98(s,1H),6.83–6.81(brs,2H) ,6.38(s,2H),6.32(d,J=7.4Hz,1H),5.22(dq,J=7.4,7.0Hz,1H),3.98–3.81(brs,2H),1.58(d,J=7.0Hz,1H).

[0060] Example 7

[0061]

[0062] Referring to the synthesis method of compound I-4, 2-chloroisonicotinic acid is replaced by 2-chloro-6-carboxylic acid pyrazine to obtain compound I-7. 1H NMR (300 MHz, CDCl 3 )δ9.32(s,1H),9.14(s,1H),8.10(d,J=8.0Hz,1H),8.04-7.98(m,2H),7.27-7.21(m,2H),7.02(s,1H ), 6.87 (s, 1H), 6.81 (s, 1H), 5.30 (dq, J = 8.0, 7.0Hz, 1H), 4.00-3.70 (brs, 2H), 1.64 (d, J = 7.0Hz, 3H).

[0063] Example 8

[0064]

[0065] Referring to the synthesis method of compound I-4, 2-chloroisonicotinic acid was replaced by 2-chloro-4-pyrimidinecarboxylic acid to obtain compound I-8 (18 mg, yield 16%). 1 H NMR (300 MHz, CDCl 3 )δ9.01(d,J=4.9Hz,1H),8.47–8.43(m,2H),8.26(d,J=7.8Hz,1H),7.98(d,J=4.9Hz,1H),7.24–7.1 8(m,2H),7.04(s,1H),6.87(s,1H),6.83(s,1H),5.28(dq,J=7.8,6.9Hz,1H),1.67(d,J=6.9Hz,3H).

[0066] Example 9

[0067]

[0068] Referring to the synthesis method of compound I-4, 2-chloroisonicotinic acid was replaced with 2-chloro-6-methoxyisonicotinic acid to obtain compound I-9 (36 mg, yield 47%). 1 H NMR (300 MHz, DMSO-d 6 )δ9.11(d,J=7.8Hz,1H),8.23–8.18(m,2H),7.93(s,1H),7.38–7.32(m,2H),7.18(s,1H),6.81(s ,2H),6.72(s,1H),5.60(s,2H),5.09(dq,J=7.8,7.0Hz,1H),4.00(s,3H),1.47(d,J=7.0Hz,3H).

[0069] Example 10

[0070]

[0071] Synthesis route:

[0072]

[0073] Synthesis of I-10b

[0074] In N 2 Under protection, 2-chloro-6-methoxyisonicotinic acid I-10a (500 mg, 2.67 mmol), p-fluorophenyl borate I-4d (889.3 mg, 4.01 mmol, 1.5 eq), tetrakistriphenylphosphine palladium (62 mg, 2 mol%), potassium carbonate (1107 mg, 8.01 mmol, 3 eq) were dissolved in 5 mL of dioxane and 1 mL of water. The reaction solution was stirred at 80 ° C overnight, diluted with water, and extracted with ethyl acetate. The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain compound I-10b (584 mg, yield 89%).

[0075] Synthesis of I-10c

[0076] I-10c (389.5 mg, 1.62 mmol) was dissolved in 3 mL of acetic acid, and 2 mL of HBr was slowly added dropwise at room temperature. The reaction solution was heated to 100°C and stirred overnight. The reaction solution was cooled to room temperature, saturated sodium bicarbonate solution was added dropwise to adjust the pH to 6-7, and the solution was filtered by suction. The filter cake was washed with water and dried to obtain compound I-10c (305 mg, yield 81%).

[0077] Synthesis of I-10

[0078] Referring to the synthesis method of compound I-4c, 2-chloroisonicotinic acid was replaced with compound I-10c to obtain white solid I-10 (157 mg, 43%). 1 H NMR (300 MHz, DMSO-d 6 )δ9.03(d,J=7.9Hz,1H),7.96-7.91(m,2H),7.38–7.32(m,2H),7.16(s,1H),6.87(s,1H), 6.81 (s, 2H), 6.71 (s, 1H), 5.60 (s, 2H), 5.05 (dq, J = 7.9, 7.1Hz, 1H), 1.46 (d, J = 7.1Hz, 3H).

[0079] Embodiment 11

[0080]

[0081] Synthesis route:

[0082]

[0083] Synthesis of I-11a

[0084] Compound I-10c (100 mg, 0.43 mmol, 1 eq) and potassium carbonate (178 mg, 1.29 mmol, 3 eq) were dissolved in 1 mL DMF, and CH 3 I (183 mg, 1.29 mmol, 3 eq. The reaction solution was stirred at 80°C for 3 h, diluted with water, and extracted with ethyl acetate. The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain compound I-11 (78.1 mg, yield 63%).

[0085] Synthesis of I-11b

[0086] Referring to the synthesis method of compound I-10c, compound I-11b can be prepared by replacing I-10b with compound I-11a.

[0087] Synthesis of I-11

[0088] Referring to the synthesis method of compound I-4c, 2-chloroisonicotinic acid was replaced with compound I-11b to obtain compound I-11 (80.4 mg, 62%). 1 H NMR (300 MHz, CDCl 3 )δ8.07–8.01(m,2H),7.61(d,J=1.1Hz,1H),7.18–7.10(m,2H),6.97(s,1H),6.90(d,J=1.1Hz,1H),6. 83(s,1H),6.81(s,1H),6.44(d,J=7.8Hz,1H),5.22–5.32(m,1H),4.04(s,3H),1.59(d,J=6.9Hz,3H).

[0089] Example 12

[0090]

[0091] Referring to the synthesis method of compound I-4, compound I-12 (80.0 mg, 56%) can be prepared by replacing 2-chloroisonicotinic acid with 6-bromo-1H-indazole-4-carboxylic acid. 1 H NMR (300 MHz, DMSO-d 6)δ13.35(d,J=12.9Hz,1H),9.05(d,J=7.8Hz,1H),8.34(d,J=4.1Hz,1H),7.96–7.95(m,1H),7.92-7.85(m,2 H),7.40–7.35(m,1H),6.89–6.83(m,2H),6.71(brs,1H),5.59(s,2H),5.19–5.08(m,2H),1.52–1.46(m,3H).

[0092] Embodiment 13

[0093]

[0094] Synthesis route:

[0095]

[0096] Synthesis of Compound I-13b

[0097] Under ice bath conditions, a solution of morpholine (231.9 mg, 2.66 mmol, 1.eq) in dichloromethane (3 mL) was slowly added dropwise to a solution of methyl 2,6-dichloropyrimidine-4-carboxylate I-13a (500 mg, 2.42 mmol) and triethylamine (0.33 mL, 2.42 mmol, 1 eq) in dichloromethane (5 mL). The reaction solution was stirred at 0°C for 5 minutes, diluted with water, and extracted with ethyl acetate. The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain I-13b (430 mg, yield 69%).

[0098] Synthesis of compound I-13c

[0099] Referring to the synthesis method of compound I-10c, compound I-13c can be prepared by replacing I-10b with compound I-13b.

[0100] Synthesis of Compound I-13

[0101] Referring to the synthesis method of compound I-4c, 2-chloroisonicotinic acid was replaced with compound I-13c to obtain compound I-13 (33.3 mg, 51%). 1 H NMR (300 MHz, CDCl 3)δ8.03(d,J=7.9Hz,1H),7.26(d,J=8.9Hz,1H),6.96(s,1H),6.81(s,1H),6.79(s,1H),5. 17(dq,J=7.9,6.9Hz,1H),4.10–3.86(brs,2H),3.86–3.52(m,8H),1.58(d,J=6.9Hz,3H).

[0102] Embodiment 14

[0103]

[0104] Synthesis route:

[0105]

[0106] Synthesis of Compound I-14a

[0107] In N 2 Under protection, compound I-13b (200 mg, 0.76 mmol), methylboronic acid (159.6 mg, 2.66 mmol, 3.5 eq), Pd 2 (dba) 3 (13.8 mg, 2 mol%), SPhos (19.2 mg, 6 mol%), potassium phosphate (407.7 mg, 1.92 mmol, 2.5 eq) were dissolved in 2 mL of toluene. The reaction solution was stirred at 100 ° C for 24 h and filtered. The filtrate was diluted with water and extracted with ethyl acetate. The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by column chromatography to obtain compound I-14a (105 mg, yield 57%).

[0108] Synthesis of compound I-14b

[0109] Referring to the synthesis method of compound I-10c, compound I-14b can be prepared by replacing I-10b with compound I-14a.

[0110] Synthesis of Compound I-14

[0111] Referring to the synthesis method of compound I-4c, 2-chloroisonicotinic acid was replaced with compound I-14b to obtain compound I-14 (68.3 mg, 49%). 1 H NMR (300 MHz, CDCl 3)δ8.33(d,J=7.9Hz,1H),7.16(s,1H),6.97(s,1H),6.82(s,1H),6.78(s,1H),5.19(dq,J=7 .9, 6.9Hz, 1H), 4.00–3.80 (brs, 2H), 3.75–3.69 (m, 8H), 2.52 (s, 3H), 1.58 (d, J = 6.9Hz, 3H).

[0112] Embodiment 15

[0113]

[0114] Referring to the synthesis method of compound I-4, compound I-15 (18.9 mg, 21%) can be prepared by replacing compound 2-chloroisonicotinic acid with 5-bromo-6-methoxypyridazine-3-carboxylic acid. 1 H NMR (300 MHz, CDCl 3 )δ8.27(d,J=8.1Hz,1H),7.46(s,1H),6.97(s,1H),6.83(s,1H),6.78(s,1H),5.21(dq,J= 8.1,7.0Hz,1H),4.21(s,3H),3.86–3.84(m,4H),3.37–3.35(m,4H),1.57(d,J=7.0Hz,3H).

[0115] Example 16

[0116]

[0117] Referring to the synthesis method of compound I-4, compound I-16 (21.3 mg, 29%) can be prepared by replacing compound 2-chloroisonicotinic acid with 3-bromobenzoic acid. 1 H NMR (300 MHz, CDCl 3 )δ7.96(s,1H),7.74–7.64(m,2H),7.60–7.46(m,3H),7.18–7.09(m,2H),6.99(s,1H),6.86(s,1H),6.80 (s,1H),6.38(d,J=8.2Hz,1H),5.29(dq,J=8.2,6.8Hz,1H),3.57–3.10(brs,2H),1.61(d,J=6.8Hz,3H).

[0118] Example 17 In vitro SOS1 protein level activity test

[0119] The compounds in the above examples inhibit SOS1 and KRAS G12C The combined activity is tested, and the specific operation is as follows:

[0120] 1. SOS1-KRAS G12C Protein Inhibitory Activity Test Process

[0121] (1) Dissolve the compound to be tested in DMSO to prepare a 10 mM stock solution. Transfer the compound stock solution to the test plate and perform a concentration gradient dilution.

[0122] (2) Prepare Tag1-SOS1 solution with dilution buffer, transfer 5 μL of Tag1-SOS1 solution to the test plate, and add 5 μL of dilution buffer to the low blank control group.

[0123] (3) Prepare Tag2-KRAS in dilution buffer G12C Solution, transfer 5 μL Tag2-KRAS G12C The solution was added to the test plate, and 5 μL of dilution buffer was added to the low blank control group.

[0124] (4) Prepare Anti-Tag1-Tb with detection buffer 3+ and Anti-Tag2-XL665 detection solution. Transfer 10 μL of the detection solution to the detection plate. Place the detection plate in a centrifuge, centrifuge at 1000 rpm for 1 min, and incubate at room temperature for 30 min.

[0125] 2. Data Analysis

[0126] Calculate the ratio of RFU 665nm / RFU 615nm and convert the ratio into a percent inhibition value. Fit the data into Excel to obtain the inhibition value using the following formula:

[0127] Inh%=(Max–Signal) / (Max–Min)×100

[0128] XL-Fit was used to fit the data and the half-inhibitory concentration was obtained using the following formula:

[0129] Y=Bottom+(Top–Bottom) / (1+(IC 50 / X)×HillSlope)

[0130] Y is the inhibition rate and X is the compound concentration.

[0131] 3. Experimental results

[0132] The specific results are shown in the table:

[0133] Compound No. <![CDATA[SOS1IC 50 (nM)]]> Compound No. <![CDATA[SOS1IC 50 (nM)]]> I-1 1263 I-9 940 I-2 389 I-10 392 I-3 332 I-11 866 1-4 385 I-12 4046 I-5 147 I-13 2729 I-6 308 I-14 2175 I-7 314 I-15 2443 I-8 462 I-16 2062 .

[0134] Embodiment 18

[0135] DLD-1(3D) cell proliferation inhibitory activity test

[0136] 1. Experimental Procedure

[0137] Colon cancer DLD-1 cells with good growth status were taken and inoculated into a 96-well plate at a density of 500 cells / well, and cultured in a 37°C, 5% carbon dioxide cell culture incubator overnight, and the compound with concentration gradient dilution was added, and the culture was continued in the incubator for 7 days, and the detection reagent (Celltiter Glo Assay kit-3D) was added to the 96-well plate (100 μL), after shaking at room temperature for 5 minutes, incubated at room temperature in the dark for 30 minutes, and then the luminescence value was read with a multifunctional microplate reader.

[0138] 2. Data Analysis

[0139] The percentage inhibition rate can be calculated according to the following formula: inhibition percentage = 100% × (0% inhibition group signal value - signal value at a specific concentration of the test compound) / (0% inhibition group signal value - 100% inhibition group signal value).

[0140] Compound IC 50 The values ​​were fitted using XL-Fit data and calculated using the following formula: Y = Bottom + (Top–Bottom) / (1+(IC 50 / X)×HillSlope), Y is the inhibition rate, and X is the concentration of the compound.

[0141] 3. Experimental results

[0142] Compound No. <![CDATA[IC 50 (μM)]]> I-5 1.0 .

Claims

1. A benzylamine compound as shown in general formula I and a pharmaceutically acceptable salt thereof, the structure of which is as follows: Ring A is selected from R 1 Selected from alkoxy, morpholine, unsubstituted or halogen-substituted benzene ring.

2. The benzylamine formyl compound and pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound is any of the following: 。 3. A pharmaceutical composition, characterized in that The invention comprises the compound according to claim 1 or 2 and a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable auxiliary material.

4. Use of the benzylamine formyl compound and the pharmaceutically acceptable salt thereof according to claim 1 or 2, and the pharmaceutical composition according to claim 3 in the preparation of SOS1 inhibitor drugs.

5. Use of the benzylamine formyl compound and a pharmaceutically acceptable salt thereof according to claim 1 or 2, and the pharmaceutical composition according to claim 3 in the preparation of a drug for preventing or treating cancer.

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