Chiral specific boron-containing compounds and their use in treating cancer or amyloidosis

Abstract

Useful chiral specific boron-containing compounds, such as boronate, boronate esters, boranamines, borane diamines, boranamine thioesters, and boronic mono/di-thioesters, have been prepared. These compounds and compositions containing them are useful as anti-cancer or anti-amyloidosis agents.

Claims

1. A compound represented by the following formula: ##STR00545## or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, a diluent, or an excipient.

3. A method of treating multiple myeloma in a human in need thereof, comprising administering to said human an effective amount of a compound of claim 1 or a pharmaceutically acceptable acid addition salt thereof.

4. A compound represented by the following formula: ##STR00546## or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a compound of claim 4 or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, a diluent, or an excipient.

6. A method of treating multiple myeloma in a human in need thereof, comprising administering to said human an effective amount of a compound of claim 4 or a pharmaceutically acceptable acid addition salt thereof.

Description

BRIEF DESCRIPTION OF THE DRAWING

(1) The FIGURE is a graph that represents the results of testing to demonstrate the cytotoxic effects of certain compounds, including compounds prepared according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

(2) The invention can perhaps be appreciated better from the description below, where compounds of the invention have been prepared and then some testing is described.

EXAMPLES

(3) Boronic acid can readily form oligomeric anhydrides by dehydration of the boronic acid moiety. Hence, the monomeric structure form drawn below, such as HL01-0 drawn in the Example 1, is expressly intended to represent the free boronic acid, oligomeric anhydrides, including, but not limited to, dimers, trimers, and tetramers, and mixtures thereof.

(4) Abbreviations: Bortezomib (HL01-0), Tetrahydrofuran (THF), Ethyl Acetate (EtOAc or EA), N,N-Dimethylsulfoxide (DMSO), Ethylenediaminetetraacetic Acid (EDTA), Hydrogen Chloride (HCl), room temperature (RT), Nuclear Magentci Resonance (NMR), Reverse Phase High Performance Liquid Chromatography (RP-HPLC), Liquid Chromatography-Mass Spectroscopy (LC-MS)

(5) General Characterization Methods: .sup.1H NMR, .sup.13C NMR, HPLC, LCMS.

(6) The product HL01-01 of Example 1, characterized by formula HL01-01-1, HL-01-01-2, HL-01-01-3, HL-01-01-4, HL-1-01-5, or a mixture thereof.

(7) ##STR00038##

(8) The product HL01-02 of Example 2, characterized by formula HL01-02-1, HL-01-02-2, HL-01-02-3, HL-01-02-4, or a mixture thereof.

(9) ##STR00039##

(10) The product HL01-17 of Example 15, characterized by formula HL01-17-1, HL-01-17-2, HL-01-17-3, HL-01-17-4, HL-1-17-5, or a mixture thereof.

(11) ##STR00040##

(12) The product HL01-18 of Example 16, characterized by formula HL01-18-1, HL-01-18-2, HL-01-18-3, HL-01-18-4, HL-1-18-5, or a mixture thereof.

(13) ##STR00041##

(14) The product HL01-23 of Example 23, characterized by formula HL01-23-1, HL-01-23-2, HL-01-23-3, HL-01-23-4, or a mixture thereof.

(15) ##STR00042##

(16) The product HL01-28 of Example 28, characterized by formula HL01-28-1, HL-01-28-2, HL-01-28-3, HL-01-28-4, or a mixture thereof.

(17) ##STR00043##

Example 1

(18) ##STR00044##

(19) Bortezomib (HL01-0, 1.0 g) was dissolved in EA (80 mL) at 85° C., and citric acid (525 mg, 2.73 mmol) was added under inert gas. The reaction mixture was stirred at 85° C. for another 3.5 hrs, then cooled to room temperature (RT), and n-Hexane (24 mL) was added. The white precipitate was filtered and dried to get the white solid HL-01-01. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 12.08 (br, 1H), 10.62 (br, 1H), 9.19 (br, 1H), 9.18 (s, 1H), 8.89 (s, 1H), 8.77 (s, 1H), 7.28-7.19 (m, 5H), 5.06 (m, 1H), 3.25 (d, 2H, J=6.8 Hz), 2.85 (m, 1H), 2.72 (m, 2H), 2.57 (m, 2H), 1.45 (m, 1H), 1.10 (m, 1H), 0.97 (m, 1H), 0.78 (d, 6H, J=4.4 Hz). .sup.13C NMR (d.sub.6-DMSO, 400 MHz) δ 177.82, 170.73, 170.62, 163.28, 147.84, 143.98, 143.71, 143.39, 129.28, 128.31, 126.79, 76.24, 50.31, 36.25, 24.55, 23.51, 21.38.

Example 2

(20) ##STR00045##

(21) HL01-0 (100 mg) was dissolved in DMSO (2 mL), and L-malic acid (35 mg, 0.26 mmol) was added under inert gas. The reaction mixture was stirred at 95° C. for 6 hrs, then cooled to RT. The solvent was removed under reduced pressure, then EA/n-Hexane was added to the residue at −20° C. The white precipitate was filtered and dried to get the white solid, HL-01-02. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 12.30 (br, 1H), 10.72 (s, 1H), 9.33 (d, 1H, J=7.6 Hz), 9.13 (d, 1H, J=1.6 Hz), 8.89 (d, 1H, J=1.6 Hz), 8.78 (m, 1H), 7.28-7.21 (m, 5H), 5.07 (dd, 1H, J=15.2, 7.6 Hz), 4.37 (dd, 1H, J=7.2, 4.0 Hz), 3.46-3.42 (m, 1H), 3.29-3.20 (m, 2H), 2.63-2.28 (m, 2H), 1.46 (m, 1H), 1.17 (m, 2H), 0.81 (d, 6H, J=6.4 Hz). MS (m/z): [M+Na] calculated for C.sub.23H.sub.27BN.sub.4NaO.sub.7, 505.28; found, 505.19.

Example 3

(22) ##STR00046##

(23) HL01-0 (200 mg) was dissolved in EA (8 mL) at 85° C., and diethanolamine (54.7 mg, 0.52 mmol) was added under inert gas. The reaction mixture was stirred at 85° C. for 6 hrs. then was cooled to RT. The white precipitate was collected and dried to get the white solid. (150 mg, 63. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.09 (s, 1H), 8.87 (d, 1H, J=2.4 Hz), 8.81 (d, 1H, J=8.8 Hz), 8.75 (s, 1H), 7.28-7.20 (m, 5H), 7.16-7.14 (m, 1H), 6.55 (br, 1H), 4.76 (td, 1H, J=9.2, 4.8 Hz), 3.69-3.61 (m, 2H), 3.28-3.23 (m, 1H), 3.48-3.41 (m, 1H), 3.16-3.04 (m, 3H), 2.85-2.77 (m, 1H), 2.74-2.67 (m, 2H), 1.63-1.53 (m, 1H), 1.37-1.30 (m, 1H), 1.22-1.16 (m, 1H), 0.80 (dd, 6H, J=12.8, 6.8 Hz).

Example 4

(24) ##STR00047##

(25) HL01-0 (384 mg) was dissolved in DMSO (3 mL) and EA (3 mL), and Iminodiacetic Acid (133 mg, 1 mmol) was added under inert gas. The reaction mixture was stirred at 85° C. for 6 hrs, then was cooled to RT. The white precipitate was collected under reduced pressure, washed by EtOH, and dried to get the white solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.09 (d, 1H, J=1.2 Hz), 8.87 (d, 1H, J=2.4 Hz), 8.73-8.72 (m, 1H), 8.70 (d, 1H, J=8.8 Hz), 8.16 (br, 1H), 7.76 (d, 1H, J=8 Hz), 7.26-7.13 (m, 5H), 4.72 (td, 1H, J=8.8, 5.6 Hz), 4.06 (dd, 1H, J=17.2, 8.4 Hz), 3.92 (dd, 1H, J=17.6, 8.4 Hz), 3.76 (dd, 1H, J=9.2, 3.2 Hz), 3.72 (dd, 1H, J=9.2, 3.2 Hz), 3.14-3.01 (m, 3H), 1.59-1.45 (m, 2H), 1.08-1.01 (m, 1H), 0.82 (dd, 6H, J=22.4, 6.8 Hz). MS (m/z): [M+H] calculated for C.sub.23H.sub.29BN.sub.5O.sub.6, 482.32; found, 482.15.

Example 5

(26) ##STR00048##

(27) HL01-0 (19.2 mg) was dissolved in DMSO (1.5 mL), and EDTA (7.3 mg, 0.05 mmol) was added under inert gas. The reaction mixture was stirred at 100° C. for 3 hrs, then was cooled to RT. The white precipitate was collected under reduced pressure, and dried get the white solid. MS (m/z): [M+H] calculated for C.sub.29H.sub.38BN.sub.6O.sub.10, 641.46; found, 641.30.

Example 6

(28) ##STR00049##

(29) HL01-0 (50 mg) was dissolved in DMSO (2 mL), and EDTA (19 mg, 0.065 mmol) was added under inert gas. The reaction mixture was stirred at 105° C. for 4 hrs., then was cooled to RT. The white precipitate was collected under reduced pressure, purified by semi-prep RP-HPLC, and dried get the white solid. MS (m/z): [M+H] calculated for C.sub.48H.sub.59B.sub.2N.sub.10O.sub.12, 989.67; found, 989.2.

Example 7

(30) ##STR00050##

(31) HL01-0 (200 mg) was dissolved in DMSO/EA (6 mL/6 mL), and N-methyliminodiacetic acid 133 mg, 0.52 mmol) as added under inert gas. The reaction mixture was stirred at 85° C. for 5 hrs, and then was cooled to RT. The white precipitate was collected under reduced pressure, and dried to get the white solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.07 (d, 1H, J=1.2 Hz), 8.92 (d, 1H, J=4.4 Hz), 8.87 (d, 1H, J=2.4 Hz), 8.74-8.73 (m, 1H), 7.30-7.23 (m, 5H), 7.20-7.15 (m, 1H), 4.70-4.64 (m, 1H), 4.22 (d, 1H, J=17.2 Hz), 4.07 (d, 1H, J=16.8 Hz), 3.98 (d, 1H, J=16.8 Hz), 3.57-3.51 (m, 2H), 3.09 (s, 1H), 3.07 (d, 1H, J=2.0 Hz), 2.82 (s, 3H), 1.59-1.53 (m, 1H), 1.43-1.36 (m, 1H), 1.22-1.16 (m, 1H), 0.84 (dd, 6H, J=11.2, 6.4 Hz). MS (m/z): [M+H] calculated for C.sub.24H.sub.31BN.sub.5O.sub.6, 496.34; found, 496.20.

Example 8

(32) ##STR00051##

(33) HL01-0 (150 mg) was dissolved in DMSO (5 mL), and N-isopropyl iminodiacetic acid (HL01-12-0, 69 mg, 0.39 mmol) as added under inert gas. The reaction mixture was stirred at 85° C. for 5 hrs, and then was cooled to RT. The solvent was removed under reduced pressure to get colorless oil. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.09 (d, 1H, J=1.6 Hz), 8.91 (d, 1H, J=8.4 Hz), 8.86 (d, 1H, J=2.4 Hz), 7.44 (d, 1H, J=9.6 Hz), 7.30-7.16 (m, 5H), 4.68-4.62 (m, 1H), 4.28 (d, 1H, J=18.0 Hz), 3.89 (dd, 2H, J=18.4, 5.2 Hz), 3.71-3.61 (m, 3H), 3.09 (s, 1H), 3.07 (d, 1H, J=2.8 Hz), 1.61-1.55 (m, 1H), 1.49-1.42 (m, 1H), 1.16 (dd, 6H, J=6.0, 2.0 Hz), 0.99 (d, 1H, J=6.8 Hz), 0.84 (dd, 6H, J=29.2, 6.8 Hz). MS (m/z): [M+H] calculated for C.sub.26H.sub.35BN.sub.5O.sub.6, 524.4; found, 524.30.

Example 9

(34) ##STR00052##

(35) HL01-0 (200 mg) was dissolved in DMSO (3 mL), and N-benzyl iminodiacetic acid (HL01-13-0, 122 mg, 0.547 mmol) as added under inert gas. The reaction mixture was stirred at 85° C. for 2 hrs, then was cooled to RT. The solvent was removed under reduced pressure to get colorless oil. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.12 (d, 1H, J=1.6 Hz), 9.06 (d, 1H, J=8.0 Hz), 8.87 (d, 1H, J=2.0 Hz), 8.75 (dd, 1H, J=2.4, 1.6 Hz), 7.63-7.61 (m, 1H), 7.52-7.50 (m, 2H), 7.34-7.17 (m, 7H), 4.66-4.60 (m, 1H), 4.465 (d, 1H, J=13.2 Hz), 4.26 (d, 1H, J=13.2 Hz), 4.18 (d, 1H, J=17.2 Hz), 3.85-3.77 (m, 2H), 3.68-3.63 (m, 1H), 3.15-3.00 (m, 3H), 1.66-1.60 (m, 1H), 1.56-1.45 (m, 1H), 1.35-1.26 (m, 1H), 0.89 (dd, 6H, J=11.2, 6.8 Hz). MS (m/z): [M+H] calculated for C.sub.30H.sub.35BN.sub.5O.sub.6, 572.44; found, 572.30.

Example 10

(36) ##STR00053##

(37) HL01-0 (200 mg) was dissolved in EA (5 mL), and Pinacol (61.5 mg) was added under inert gas. The reaction mixture was stirred at 85° C. for 5 hrs, and then was cooled to RT, and the solvent was removed under reduced pressure to get the oil. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.18 (d, 1H, J=1.2 Hz), 8.99-8.98 (m, 1H), 8.94 (d, 1H, J=2.8 Hz), 8.84 (d, 1H, 8.4 Hz), 8.91-8.80 (m, 1H), 7.33-7.23 (m, 5H), 4.96-4.91 (m, 1H), 3.19-3.17 (m, 2H), 2.70-2.66 (m, 1H), 1.65-1.56 (m, 1H), 1.37-1.31 (m, 1H), 1.27-1.23 (m, 1H), 1.18 (d, 12H, J=4.8 Hz), 0.88 (t, 6H, J=6.4 Hz). MS (m/z): [M+H] calculated for C.sub.25H.sub.36BN.sub.4O.sub.4, 467.28; found: 467.30.

Example 11

(38) ##STR00054##

(39) Chloroacetic acid (6 g, 0.0625 mol) was dissolved in water (20 mL) at 0° C., then neutralized with 5 N NaOH solution. Isopropylamine (1.85 g, 0.031 mol) was added to the solution and stirred at 50° C. overnight. BaCl.sub.2 2H.sub.2O (7.6 g, 0.031 mol) was dissolved in hot water (15 mL) and was added to the reaction mixture. The precipitate was filtered and dried at 60° C. for 2 hours. The solid was dissolved in the boiling water, and 5N H.sub.2SO.sub.4 was added. After removal of the precipitate, the filtrate was concentrated to give brown solid, HL01-12-0 (300 mg, 5.5%) H NMR (d6-DMSO, 400 MHz) δ 3.27 (s, 4H), 3.12 (s, 1H), 1.02 (s, 6H).

Example 12

(40) ##STR00055##

(41) Chloroacetic acid (18.9 g, 0.2 mol) was dissolved in water (30 mL) at 0° C., then neutralized with 5 N NaOH solution. Benzylamine (10.7 g, 0.1 mol) was added to the solution and stirred at 60° C. overnight. BaCl.sub.2 2H.sub.2O (25.6 g, 0.105 mol) was dissolved in hot water (30 mL) and was added to the reaction mixture. The precipitate was filtered and dried at 80° C. for 4 hours. The solid was dissolved in the boiling water, and 5N H.sub.2SO.sub.4 was added. After removal of the precipitate, the filtrate was concentrated to give white solid, HL01-13-0 (8.0 g, 36%). .sup.1H NMR (d6-DMSO, 400 MHz) δ 7.33-7.24 (m, 5H), 3.82 (s, 2H), 3.38 (s, 4H).

Example 13

(42) ##STR00056##

(43) HL01-00 (30 mg, 0.083) was dissolved in DMSO (2 mL), and N-Methyl iminodiacetic acid (12.2 mg, 0.083 mmol) was added under inert gas. The reaction mixture was stirred at 85° C. for 2 hrs, then was cooled to RT. The solvent was removed under reduced pressure and the residue purified by Prep-HPLC to get the white solid, HL01-15 (15 mg, 38.5%).sup.1H NMR (d6-DMSO, 400 MHz) δ 8.84 (s, 1H), 7.54-7.52 (m, 3H), 7.33 (d, 1H, J=8.8 Hz), 4.26-4.13 (m, 3H), 4.02-3.80 (m, 4H), 2.87 (s, 3H), 1.53-1.52 (m, 1H), 1.41-1.35 (m, 1H), 1.20-1.16 (m, 1H), 0.85 (m, 6H). MS (m/z): [M+H] calculated for C.sub.19H.sub.25BCl.sub.2N.sub.3O.sub.6, 472.12; found, 472.00.

Example 14

(44) ##STR00057##

(45) HL01-000 (30 mg) was dissolved in DMSO (2 mL), and N-Methyl iminodiacetic acid (10.7 mg, 0.073 mmol) was added under inert gas. The reaction mixture was stirred at 85° C. for 2 hrs, then was cooled to RT. The solvent was removed under reduced pressure and the residue was purified by Prep-HPLC to get the white solid, HL01-17 (10 mg, 36.3%). .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 8.80 (d, 1H, J=8.4 Hz), 8.21-8.17 (m, 3H), 8.11 (t, 1H, J=8.0 Hz), 8.00 (d, 1H, J=6.8 Hz), 7.59-7.25 (m, 4H), 5.21-5.20 (m, 1H), 4.51 (dd, 1H, J=8.4, 3.6 Hz), 4.28 (d, 1H, J=17.6 Hz), 4.12 (d, 1H, J=16.8 Hz), 4.08 (br, 1H), 3.97 (d, 1H, J=17.2 Hz), 3.92 (d, 1H, J=16.4 Hz), 2.94 (s, 3H), 1.55-1.48 (m, 1H), 1.45-1.37 (m, 1H), 1.22-1.15 (m, 1H), 1.09 (d, 3H, J=6.0 Hz), 0.82 (dd, 6H, J=16.8, 6.8 Hz). MS (m/z): [M+H] calculated for C.sub.26H.sub.34BN.sub.4O.sub.7, 525.25; found, 525.30.

Example 15

(46) ##STR00058##

(47) To a solution of HL01-00 (30 mg) in EA (2 mL) was added citric acid (16 mg, 0.083 mmol) at sealed tube. The reaction mixture was stirred at 85° C. for 1.5 hrs. The reaction mixture was cooled to RT, and the solid was filtered to get the product white solid, HL01-17. (˜15 mg, 35.7%).sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 12.18 (br, 1H), 10.72 (s, 1H), 9.13 (s, 1H), 7.66 (s, 1H), 7.57 (d, 2H, J=1.2 Hz), 4.27 (br, 2H), 2.92-2.88 (m, 1H), 2.78-2.74 (m, 1H), 2.67-2.63 (m, 1H), 2.53 (s, 1H), 1.68-1.67 (m, 1H), 1.29-1.77 (m, 3H), 0.87 (d, 6H, J=6.4 Hz).

Example 16

(48) ##STR00059##

(49) HL01-000 (30 mg) was dissolved in DMSO (2 mL) at RT, and then citrate (14 mg, 0.073 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 4 hrs, then cooled to RT, The solvent was removed to get solid (15 mg). .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 12.14 (s, 1H), 10.78 (s, 1H), 8.81-8.79 (d, 1H, J=8.4 Hz), 8.24-8.19 (m, 3H), 8.15-8.11 (t, 1H), 8.04-8.03 (d, 1H, J=7.2 Hz), 7.58-7.49 (m, 3H), 5.7 (s, 1H), 4.72-4.69 (dd, 1H), 4.27 (s, 1H), 2.90-2.67 (m, 4H), 1.62 (s, 1H), 1.30-1.14 (d, 5H), 0.83-0.82 (d, 6H, J=6.4 Hz)

Example 17

(50) ##STR00060##

(51) HL01-000 (30 mg) was dissolved in DMSO (2 mL) at RT, and then iminodiacetic acid (9.71 mg, 0.073 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT. The solvent was removed to get white crystalline solid, HL01-19 (15 mg). .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 8.78-8.76 (d, 1H, J=8.0 Hz), 8.21-8.16 (m, 3H), 8.12-8.08 (t, 2H), 8.02-8.00 (d, 1H), 7.74-7.73 (d, 1H, J=7.6 Hz), 7.58-7.49 (m, 3H), 5.16 (s, 1H), 4.41-4.38 (q, 1H), 4.15-4.07 (m, 3H), 3.79-3.72 (m, 2H), 3.19-3.13 (m, 1H), 1.65-1.62 (m, 1H), 1.56-1.48 (m, 1H), 1.11-1.04 (m, 3H), 0.86-0.85 (d, 3H=6.8 Hz), 0.80-0.78 (d, 3H, J=6.4 Hz). MS (m/z): [M+H] calculated for C.sub.25H.sub.32BN.sub.4O.sub.7, 511.35; found, 511.0.

Example 18

(52) ##STR00061##

(53) HL01-000 (30 mg) was dissolved in DMSO (2 mL) at RT, and Pinacol (8.61 mg, 0.073 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT. The solvent was removed to get solid, HL01-20 (10 mg). .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.11 (s, 1H), 8.78-8.76 (d, 1H, J=8.4 Hz), 8.23-8.19 (m, 3H), 8.13-8.10 (t, 1H), 8.03-8.01 (d, 1H, J=7.2 Hz), 7.57-7.50 (m, 4H), 5.32-5.31 (d, 1H, J=4.8 Hz), 4.55-4.51 (dd, 1H), 4.15-4.11 (dd, 1H), 1.68-1.64 (m, 1H), 1.29-1.20 (m, 2H), 1.14-1.09 (m, 12H), 0.85-0.83 (dd, 6H)

Example 19

(54) ##STR00062##

(55) HL01-000 (30 mg) was dissolved in DMSO (2 mL) at RT, and N-isopropyl iminodiacetic (8.61 mg, 0.073 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, and then cooled to RT. The solvent was removed to get pale yellow sticky solid, HL01-21. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 8.76-8.74 (d, 1H, J=8.4 Hz), 8.18-8.16 (m, 3H), 8.12-8.08 (t, 1H), 8.02-8.00 (d, 1H), 7.59-7.51 (m, 4H), 5.17 (s, 1H), 4.56-4.53 (dd, 1H), 4.33-4.28 (d, 1H), 4.08 (s, 1H), 3.99-3.89 (d, 3H), 3.83-3.80 (t, 1H), 3.71-3.67 (t, 1H), 1.59-1.37 (m, 3H), 1.23-1.10 (dd, 6H), 0.86-0.79 (m, 6H) MS (m/z): [M+H] calculated for C.sub.28H.sub.38BN.sub.4O.sub.7, 553.43; found, 553.3.

Example 20

(56) ##STR00063##

(57) HL01-000 (30 mg) was dissolved in DMSO (2 mL) at RT, and EDTA (10.65 mg, 0.037 mmol) was added, the reaction mixture was stirred at 98° C. under inert gas for another 6 hrs, then cooled to RT. The solvent was removed to get solid which was purified by RP-HPLC to give HL01-220-1 and dimer HL01-22-2. HL01-22-1 MS (m/z): [M+H] calculated for C.sub.31H.sub.41BN.sub.5O.sub.14, 670.28; found, 670.2. HL01-22-2 MS (m/z): [M+H] calculated for C.sub.52H.sub.65B.sub.2N.sub.8O.sub.14, 1047.47; found, 1047.1.

Example 21

(58) ##STR00064##

(59) HL01-000 (30 mg) was dissolved in DMSO (2 mL) at RT, and L-malic acid (9.79 mg, 0.073 mmol) was added, the reaction mixture was stirred at 98° C. under inert gas for another 6 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 12.30 (s, 1H), 10.87 (s, 1H), 8.83-8.81 (d, 1H, J=8 Hz), 8.24-8.02 (m, 5H), 7.59-7.52 (m, 3H), 5.77-5.76 (d, 1H, J=5.2 Hz), 4.76-4.73 (m, 1H), 4.41-4.39 (m, 1H), 4.32-4.29 (m, 1H), 2.68-2.57 (m, 2H), 1.63-1.56 (m, 1H), 1.31-1.26 (t, 2H), 1.19-1.18 (d, 3H, J=6.4 Hz), 0.84-0.83 (d, 6H, J=6.4 Hz)

Example 22

(60) ##STR00065##

(61) HL01-00 (30 mg) was dissolved in DMSO (2 mL) at RT, and Iminodiacetic Acid (11.03 mg, 0.083 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d6-DMSO, 400 MHz) δ 8.75-8.72 (t, 1H), 8.19 (s, 1H), 7.69-7.68 (m, 1H), 7.52-7.51 (d, 2H, J=1.2 Hz), 4.15-4.0 (m, 2H), 3.88-3.72 (m, 4H), 3.14-3.08 (m, 1H), 1.65-1.62 (m, 1H), 1.54-1.46 (m, 1H), 1.12-1.06 (m, 1H), 0.88-0.81 (dd, 6H, J=6.8, 21.6 Hz). MS (m/z): [M+H] calculated for C18H22BCl2N3O6, 458.09; found, 458.4.

Example 23

(62) ##STR00066##

(63) HL01-00 (30 mg) was dissolved in EA (2 mL) at RT, and pinacol (9.79 mg, 0.083 mmol) was added. The reaction mixture was stirred at 98° C. under inert gas for another 6 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.07 (s, 1H), 8.88-8.85 (t, 1H), 7.70 (s, 1H), 7.53 (s, 2H), 4.04-4.02 (d, 2H, J=6 Hz), 2.66-2.57 (m, 1H), 1.71-1.67 (m, 2H), 1.52-1.47 (m, 1H), 1.08 (s, 12H), 0.87-0.84 (t, 6H)

Example 24

(64) ##STR00067##

(65) HL01-00 (30 mg) was dissolved in DMSO (1 mL) at RT, and N-isopropyl iminodiacetic acid (14.53 mg, 0.083 mmol) was added. The reaction mixture was stirred at 98° C. under inert gas for another 6 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 8.78 (s, 1H), 7.68 (s, 1H), 7.49-7.47 (d, 3H, J=8 Hz), 4.32-4.28 (d, 1H, J=16.8 Hz), 4.05-3.88 (m, 4H), 3.74-3.67 (m, 3H), 1.54 (s, 1H), 1.44-1.38 (t, 2H), 1.23-1.06 (m, 7H), 0.86-0.82 (d, 6H, J=15.2 Hz). MS (m/z): [M+H] calculated for C.sub.21H.sub.29BCl.sub.2N.sub.3O.sub.6, 501.18; found, 502.1.

Example 25

(66) ##STR00068##

(67) HL01-00 (30 mg) was dissolved in DMSO (1 mL) at RT, and EDTA (24.23 mg, 0.083 mmol) was added. The reaction mixture was stirred at 98° C. under inert gas for another 6 hrs, then cooled to RT. The solvent was removed to get solid which was purified by RP-HPLC to obtain HL01-27-1 and dimer HL01-27-2. HL01-27-1 MS (m/z): [M+H] calculated for C.sub.24H.sub.32BCl.sub.2N.sub.4O.sub.10, 618.24; found, 618.4; HL01-27-2 MS (m/z): [M+H] calculated for C.sub.38H.sub.47B.sub.2Cl.sub.4N.sub.6O.sub.2, 943.24; found: 943.4.

Example 26

(68) ##STR00069##

(69) HL01-00 (30 mg) was dissolved in DMSO (1 mL) at RT, and L-malic acid (11.12 mg, 0.083 mmol) was added. The reaction mixture was stirred at 98° C. under inert gas for another 6 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.4-CD.sub.3OD, 400 MHz) δ 7.59-7.56 (t, 2H), 7.46 (dd, 1H, J=2 Hz, 8.4 Hz), 4.591-4.565 (q, 1H), 4.37 (s, 2H), 2.87-2.78 (m, 2H), 2.61-2.58 (m, 1H), 1.74-1.64 (m, 1H), 1.47-1.43 (t, 2H), 0.96-0.94 (dd, 6H, J=2.8 Hz, 6.8 Hz)

Example 27

(70) ##STR00070##

(71) HL01-00 (30 mg) was dissolved in DMSO (1 mL) at RT, and Nitrilotriacetic acid (15.85 mg, 0.083 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 8.81-8.78 (t, 1H), 7.69-7.68 (t, 1H), 7.50-7.38 (m, 3H), 4.43-4.38 (d, 1H, J=20 Hz), 4.30-4.25 (d, 1H, J=16.8 Hz), 4.21-4.00 (m, 4H), 3.91-3.86 (dd, 1H, J=5.2 Hz, 15.6 Hz), 3.68-3.63 (dd, 1H, J=6.4 Hz, 16 Hz), 3.59-3.53 (m, 1H), 1.56-1.53 (m, 1H), 1.39-1.36 (m, 1H), 1.21-1.17 (m, 1H), 0.85 (dd, 6H, J=6.4 Hz, 14 Hz). MS (m/z): [M+H] calculated for C.sub.20H.sub.25BCl.sub.2N.sub.3O.sub.8, 517.14; found, 517.3.

Example 28

(72) ##STR00071##

(73) HL01-000 (30 mg) was dissolved in DMSO (1 mL) at RT, and Nitrilotriacetic acid (13.94 mg, 0.073 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 8.83-8.78 (t, 1H), 8.22-8.18 (t, 2H), 8.12-8.08 (t, 1H), 8.03-7.98 (t, 1H), 7.59-7.48 (m, 5H), 4.53-4.50 (m, 1H), 4.46-4.42 (d, 1H, J=17.6 Hz), 4.35-4.02 (m, 4H), 3.61-3.55 (m, 1H), 3.50 (s, 2H), 1.55-1.46 (m, 1H), 1.45-1.38 (m, 2H), 1.10-1.08 (d, 3H, J=6.4 Hz), 0.85-0.79 (m, 6H). MS (m/z): [M+H] calculated for C.sub.27H.sub.34BN.sub.4O.sub.9, 569.38; found, 569.5.

Example 29

(74) ##STR00072##

(75) HL01-0 (30 mg) was dissolved in DMSO (1 mL) at RT, and Nitrilotriacetic acid (14.89 mg, 0.078 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 6 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.07-9.06 (d, 1H, J=1.2 Hz), 8.92-8.83 (m, 2H), 8.74-8.70 (m, 1H), 7.40-7.38 (d, 1H, J=10 Hz), 7.29-7.12 (m, 5H), 4.71-4.65 (m, 1H), 4.40-4.04 (m, 4H), 3.55-3.55 (m, 3H), 3.09-3.06 (m, 2H), 1.60-1.51 (m, 1H), 1.45-1.38 (m, 1H), 1.23-1.17 (m, 1H), 0.84 (dd, 6H, J=6.4 Hz, 18.4 Hz). MS (m/z): [M+H] calculated for C.sub.25H.sub.31BN.sub.5O.sub., 540.35; found, 540.3.

Example 30

(76) ##STR00073##

(77) HL01-0 (30 mg) was dissolved in DMSO (1 mL) at RT, and L(+)-tartaric acid (11.70 mg, 0.078 mmol) was added, The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT, The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ12.75 (bs, 1H), 10.77 (s, 1H), 9.38-9.35 (t, 1H), 9.12 (s, 1H), 8.90-8.89 (d, 1H, J=2.4 Hz), 8.78-8.77 (t, 1H), 7.29-7.18 (m, 5H), 5.12-5.07 (q, 1H), 4.49-4.21 (q, 2H), 3.32-3.21 (m, 2H), 2.68-2.57 (m, 1H), 1.55-1.37 (m, 1H), 1.23-1.06 (m, 2H), 0.86-0.79 (q, 6H).

Example 31

(78) ##STR00074##

(79) HL01-0 (60 mg) was dissolved in Ethyl acetate (1 mL) at RT, and N-methyldiethanolamine (18.56 mg, 0.156 mmol) was added. The reaction mixture was stirred at RT under inert gas for another 5 hrs, then solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.24-9.22 (d, 1H, J=8.4 Hz), 9.09-9.08 (d, 1H, J=1.2 Hz), 8.89-8.88 (d, 1H, J=2.4 Hz), 8.79-8.78 (m, 1H), 7.30-7.12 (m, 5H), 6.74-6.72 (d, 1H, J=10 Hz), 4.67-4.61 (m, 1H), 3.61-3.55 (m, 3H), 3.21-3.0 (m, 6H), 2.90-2.86 (m, 1H), 1.55-1.49 (m, 1H), 1.23-1.15 (m, 2H), 0.84-0.78 (dd, 6H, J=6.4, 16 Hz). 3H (N-Me) was contained in 2.5 (DMSO)

Example 32

(80) ##STR00075##

(81) HL01-0 (30 mg) was dissolved in DMSO (1 mL) at RT, and N-ethyl-iminodiacetic acid (12.57 mg, 0.078 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 9.12-9.08 (m 1H), 8.93-8.84 (m, 2H), 8.74-8.66 (m, 1H), 7.35-7.12 (m, 5H), 4.93-4.87 (q, 1H), 4.81-4.75 (q, 1H), 4.71-4.65 (q, 1H), 4.18-3.93 (m, 4H), 3.30-3.24 (q, 1H), 3.14-3.03 (m, 2H), 1.56-1.49 (m, 1H), 1.41-1.25 (m, 2H), 1.22-1.13 (m, 3H), 0.86-0.74 (m, 6H).

Example 33

(82) ##STR00076##

(83) HL01-00 (30 mg) was dissolved in ethyl acetate (1 mL) at RT, and N-methyldiethanolamine (9.87 mg, 0.083 mmol) was added, then the reaction mixture was stirred at RT under inert gas for another 5 hrs. The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ 8.94-8.91 (t, 1H), 7.72 (s, 1H), 7.56-7.45 (m, 1H), 6.51-6.48 (d, 1H, J=9.6 Hz), 3.77-3.62 (m, 6H), 3.20-3.11 (m, 3H), 2.94-2.91 (m, 1H), 2.85-2.81 (m, 1H), 2.59 (s, 3H), 1.49 (s, 1H), 1.22-1.17 (m, 2H), 0.84-0.79 (dd, 6H, J=6, 16.8 Hz). MS (m/z): [M+H] calculated for C.sub.19H.sub.29BCl.sub.2N.sub.3O.sub.4, 445.16; found, 445.4.

Example 34

(84) ##STR00077##

(85) HL01-00 (30 mg, 0.078 mmol) was dissolved in DMSO (1 mL) at RT, and N-ethyl-iminodiacetic acid (12.57 mg, 0.078 mmol) was added. The reaction mixture was stirred at 85° C. under inert gas for another 5 hrs, then cooled to RT, The solvent was removed to get solid. .sup.1H NMR (d.sub.6-DMSO, 400 MHz) δ8.78-8.66 (dt, 1H), 7.69 (s, 1H), 7.52-7.44 (m, 2H), 7.35-7.29 (m, 1H), 4.19-3.82 (m, 6H), 3.18-3.09 (m, 2H), 2.99 (s, 1H), 1.61-1.43 (m, 1H), 1.38-1.28 (m, 2H), 1.20-1.11 (m, 3H), 0.87-0.82 (m, 6H).

(86) In addition to the foregoing, the above reaction schemes, and variations thereof, can be used to prepare the compounds set forth in the following table:

(87) TABLE-US-00001 TABLE 1 Serial # Structure Name HL-40 isopropyl (S)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4-carboxylate HL-41 isopropyl 2-((S)-2-((R)- 3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4-yl)acetate HL-42 0 tert-butyl (S)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-43 tert-butyl 2-((S)-2-((R)- 3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-44 ethane-1,2-diyl (4S,4′S)-bis(2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate) HL-45 ethane-1,2-diyl bis(2- ((S)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate) HL-46 ethane-1,2-diyl bis(2- ((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4- yl)acetate) HL-47 ethane-1,2-diyl bis(2- ((S)-2-((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate) HL-48 ethane-1,2-diyl(4S,4′S)- bis(2-((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate) HL-49 ethane-1,2-diyl (4S,4′S)-bis(2-((R)-1- (2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxylate) HL-50 tert-butyl 2-((S)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-51 (S)-tert-butyl 2-((R)-1- (2-(2,5-dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-52 0 isopropyl (S)-2-((R)-1- (2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-53 isopropyl 2-((S)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-54 (S)-methyl 2-((R)-1- (2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-55 methyl 2-((S)-2-((R)-1- (2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-56 (S)-methyl 2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-57 methyl 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-58 (S)-isopropyl 2-((R)-1- ((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-59 isopropyl 2-((S)-2-((R)- 1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-60 (S)-tert-butyl 2-((R)-1- ((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-61 tert-butyl 2-((S)-2-((R)- 1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-62 00 N-((S)-1-(((R)-3- methyl-1-((R)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 2-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-63 01 N-((S)-1-(((R)-3- methyl-1-((R)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-64 02 N-((S)-1-(((R)-1-((R)-4- (isopropylcarbamoyl)- 6-oxo-1,3,2- dioxaborinan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-65 03 N-((S)-1-(((R)-1-((R)-4- (2-(isopropylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-66 04 N-((S)-1-(((R)-1-((R)-4- (tert-butylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-67 05 N-((S)-1-(((R)-1-((R)-4- (2-(tert-butylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-68 06 N,N-ethane-1,2-diyl (4R,4′R)-bis(2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxamide) HL-69 07 N,N-ethane-1,2-diyl bis(2-((R)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetamide) HL-70 08 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- N-methyl-6-oxo-1,3,2- dioxaborinane-4- carboxamide HL-71 09 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-72 0 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- N-isopropyl-6-oxo- 1,3,2-dioxaborinane-4- carboxamide HL-73 2,5-dichloro-N-(2-(((R)- 1-((R)-4-(2- (isopropylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-74 (R)-N-(tert-butyl)-2- ((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxamide HL-75 N-(2-(((R)-1-((R)-4-(2- (tert-butylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)-2,5- dichlorobenzamide HL-76 (4R,4′R)-N,N′-(ethane- 1,2-diyl)bis(2- ((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxamide) HL-77 N,N-ethane-1,2-diyl bis(2-((R)-2-((R)-1-(2- (2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4- yl)acetamide) HL-78 N,N-ethane-1,2- diyl(4R,4′R)-bis(2-((R)- 1-((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxamide) HL-79 N,N-ethane-1,2-diyl (4R,4′R)-bis(2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxamide) HL-80 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-81 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-82 0 N-((2S,3R)-3-hydroxy- 1-(((R)-1-((R)-4- (isopropylcarbamoyl)- 6-oxo-1,3,2- dioxaborinan-2-yl)-3- methylbutyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-83 N-((2S,3R)-3-hydroxy- 1-(((R)-1-((R)-4-(2- (isopropylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2-yl)-3- methylbutyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-84 N-((2S,3R)-1-(((R)-1- ((R)-4-(tert- butylcarbamoyl)-6-oxo- 1,3,2-dioxaborinan-2- yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6-phenylpicolinamide HL-85 N-((2S,3R)-1-(((R)-1- ((R)-4-(2-(tert- butylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-86 isopropyl (R)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-87 methyl (R)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-88 methyl 2-((R)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-89 isopropyl (R)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-90 isopropyl 2-((R)-2-((R)- 3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-91 tert-butyl (R)-2-(R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-92 0 tert-butyl 2-((R)-2-((R)- 3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-93 ethane-1,2-diyl (4R,4′R)-bis(2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate) HL-94 ethane-1,2-diyl (4R,4′R)-bis(2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate) HL-95 2-((R)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-96 2-((S)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-97 (S)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-98 (R)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-99 2-((R)-4- (methoxycarbonyl)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-100 2-((S)-4- (methoxycarbonyl)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-101 2-((R)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-102 0 2-((S)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-103 (S)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-104 (R)-4-(2-methoxy-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-105 2-((S)-4- (methoxycarbonyl)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-106 2-((R)-4- (methoxycarbonyl)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-107 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-108 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-109 (S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-110 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-111 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-112 0 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-113 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-114 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-115 (S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-116 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-methoxy-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-117 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-118 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-119 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamide) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-5- oxo-1,3,2-dioxaborolan- 4-yl)acetic acid HL-120 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-5- oxo-1,3,2-dioxaborolan- 4-yl)acetic acid HL-121 (S)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-6- oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-122 0 (R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-6- oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-123 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-124 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-125 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-5- oxo-1,3,2-dioxaborolan- 4-yl)acetic acid HL-126 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-5- oxo-1,3,2-dioxaborolan- 4-yl)acetic acid HL-127 (S)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-6- oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-128 (R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- methoxy-2-oxoethyl)-6- oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-129 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-130 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methoxycarbonyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-131 2-((S)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-132 0 2-((R)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-133 (R)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-134 (S)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-135 2-((R)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-136 2-((S)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-137 2-((S)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-138 2-((R)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-139 (R)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-140 (S)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-141 2-((S)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-142 0 2-((R)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-143 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-144 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-145 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-146 (S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-147 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-148 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-149 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-150 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-151 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-152 0 (S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-153 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-154 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-155 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-156 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-157 (R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-158 (S)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-159 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-160 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-161 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-162 00 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-163 01 (R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-164 02 (S)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4-(2- (methylamino)-2- oxoethyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-165 03 2-((S)-2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-166 04 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-4- (methylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 4-yl)acetic acid HL-167 05 2-((S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-168 06 2-((R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-169 07 (R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-170 08 (S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-171 09 2-((R)-4- (dimethylcarbamoyl)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-172 0 2-((S)-4- (dimethylcarbamoyl)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-173 2-((S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-174 2-((R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetic acid HL-175 (R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-176 (S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylic acid HL-177 2-((S)-4- (dimethylcarbamoyl)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-178 2,2′-(2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolane-4,4- diyl)bis(N,N- dimethylacetamide) HL-179 N-((S)-1-(((R)-1-((R)-4- (2-(dimethylamino)-2- oxoethyl)-4- (dimethylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-180 N-((S)-1-(((R)-1-((S)-4- (2-(dimethylamino)-2- oxoethyl)-4- (dimethylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-181 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-182 0 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-183 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-184 (S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-185 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(dimethylcarbamoyl)- 6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-186 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(dimethylcarbamoyl)- 6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-187 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-188 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-189 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-190 (S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-191 2-((S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(dimethylcarbamoyl)- 6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-192 0 2-((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(dimethylcarbamoyl)- 6-oxo-1,3,2- dioxaborinan-4- yl)acetic acid HL-193 (R)-2,2′-(2-(1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolane-4,4- diyl)bis(N,N- dimethylacetamide) HL-194 (R)-2,2′-(2-(1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolane-4,4- diyl)bis(N,N- dimethylacetamide) HL-195 (R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-N,N- dimethyl-6-oxo-1,3,2- dioxaborinane-4- carboxamide HL-196 (S)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 4-(2-(dimethylamino)- 2-oxoethyl)-N,N- dimethyl-6-oxo-1,3,2- dioxaborinane-4- carboxamide HL-197 2-((S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-198 2-((R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-199 (R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-200 (S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-201 2-((R)-4- (dimethylcarbamoyl)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinan-4- yl)acetic acid HL-202 0 2-((S)-4- (dimethylcarbamoyl)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinan-4- yl)acetic acid HL-203 2-((S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-204 2-((R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetic acid HL-205 (R)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-206 (S)-4-(2- (dimethylamino)-2- oxoethyl)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylic acid HL-207 2-((S)-4- (dimethylcarbamoyl)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinan-4- yl)acetic acid HL-208 2-((R)-4- (dimethylcarbamoyl)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinan-4- yl)acetic acid HL-209 2,2′-(2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolane- 4,4-diyl)bis(N,N- dimethylacetamide) HL-210 2,2′-(2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolane- 4,4-diyl)bis(N,N- dimethylacetamide) HL-211 N-((2S,3R)-1-(((R)-1- ((R)-4-(2- (dimethylamino)-2- oxoethyl)-4- (dimethylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-212 0 N-((2S,3R)-1-(((R)-1- ((S)-4-(2- (dimethylamino)-2- oxoethyl)-4- (dimethylcarbamoyl)-6- oxo-1,3,2-dioxaborinan- 2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-213 methyl (4R,5R)-5- hydroxy-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-214 methyl (4R,5S)-5- hydroxy-2-((R)-3- methyl-1-((S)-3-phenyl- 2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-215 methyl (R)-2-hydroxy- 2-((R)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-216 methyl (R)-2-hydroxy- 2-((R)-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-217 methyl (4R,5R)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-hydroxy-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-218 methyl (4R,5S)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-hydroxy-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-219 methyl (4R,5S)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-hydroxy-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-220 methyl (R)-2-((R)-2- ((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4-yl)-2- hydroxyacetate HL-222 methyl (4R,5R)-5- hydroxy-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-223 0 methyl (4R,5S)-5- hydroxy-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-224 methyl (R)-2-hydroxy- 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-225 methyl (R)-2-hydroxy- 2-((R)-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-226 methyl (4R,5R)-5- amino-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-227 methyl (4R,5S)-5- amino-2-((R)-3-methyl- 1-((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-228 methyl (R)-2-amino-2- ((R)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-229 methyl (R)-2-amino-2- ((R)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-230 methyl (4R,5R)-5- amino-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-231 methyl (4R,5S)-5- amino-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-232 methyl (R)-2-amino-2- ((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-233 0 methyl (R)-2-amino-2- ((R)-2-((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-234 methyl (4R,5R)-5- amino-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-235 methyl (4R,5S)-5- amino-2-((R)-1- ((2S,3R)-3-hydroxy-2- (6-phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-236 methyl (R)-2-amino-2- ((R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-237 methyl (R)-2-amino-2- ((R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-238 methyl (4R,5R)-2-((R)- 3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5- (methylamino)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-239 methyl (4R,5S)-2-((R)- 3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5- (methylamino)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-240 methyl (R)-2-((R)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4-yl)-2- (methylamino)acetate HL-241 methyl (R)-2-((R)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4-yl)-2- (methylamino)acetate HL-242 methyl (4R,5R)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-(methylamino)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-243 0 methyl (4R,5S)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-(methylamino)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-244 methyl (R)-2-((R)-2- ((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4-yl)-2- (methylamino)acetate HL-245 methyl (R)-2-((R)-2- ((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4-yl)-2- (methylamino)acetate HL-246 methyl (4R,5R)-2-((R)- 1-((2S,3R)-3-hydroxy- 2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5- (methylamino)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-247 methyl (4R,5S)-2-((R)- 1-((2S,3R)-3-hydroxy- 2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5- (methylamino)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-248 methyl (R)-2-((R)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6 phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)-2- (methylamino)acetate HL-249 methyl (R)-2-((R)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)-2- (methylamino)acetate HL-250 methyl (4R,5R)-5- (dimethylamino)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-251 methyl (4R,5S)-5- (dimethylamino)-2- ((R)-1-((2S,3R)-3- hydroxy-2-(6 phenylpicolinamido) butanamido)-3- methylbutyl)-6-oxo- 1,3,2-dioxaborinane-4- carboxylate HL-252 methyl (R)-2- (dimethylamino)-2- ((R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-253 0 methyl (R)-2- (dimethylamino)-2- ((R)-2-((R)-1-((2S,3R)- 3-hydroxy-2-(6- phenylpicolinamido) butanamido)-3- methylbutyl)-5-oxo- 1,3,2-dioxaborolan-4- yl)acetate HL-254 methyl (4R,5R)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-(dimethylamino)-6- oxo-1,3,2- dioxaborinane-4- carboxylate HL-255 methyl (4R,5S)-2-((R)- 1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-(dimethylamino)-6- oxo-1,3,2- dioxaborinane-4- carboxylate HL-256 methyl (R)-2-((R)-2- ((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4-yl)-2- (dimethylamino)acetate HL-257 methyl (R)-2-((R)-2- ((R)-1-(2-(2,5- dichlorobenzamido) acetamido)-3-methylbutyl)- 5-oxo-1,3,2- dioxaborolan-4-yl)-2- (dimethylamino)acetate HL-258 methyl (4R,5R)-5- (dimethylamino)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-259 methyl (4R,5S)-5- (dimethylamino)-2- ((R)-3-methyl-1-((S)-3- phenyl-2-(pyrazine-2- carboxamido)propanamido) butyl)-6-oxo-1,3,2- dioxaborinane-4- carboxylate HL-260 methyl (R)-2- (dimethylamino)-2- ((R)-2-(R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-261 methyl (R)-2- (dimethylamino)-2- ((R)-2-((R)-3-methyl-1- ((S)-3-phenyl-2- (pyrazine-2- carboxamido)propanamido) butyl)-5-oxo-1,3,2- dioxaborolan-4- yl)acetate HL-262 N-((S)-1-(((R)-1-((R)- 5,6-dimethyl-4,8-dioxo- 1,3,6,2-dioxazaborocan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-263 00 2,5-dichloro-N-(2-(((R)- 1-((R)-5,6-dimethyl- 4,8-dioxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-264 01 N-((2S,3R)-1-(((R)-1- ((R)-5,6-dimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-265 02 N-((S)-1-(((R)-1-((R)- 5,6-dimethyl-4,8-dioxo- 1,3,6,2-dioxazaborocan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-266 03 2,5-dichloro-N-(2-(((R)- 1-((R)-5,6-dimethyl- 4,8-dioxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-267 04 N-((2S,3R)-1-(((R)-1- ((R)-5,6-dimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-268 05 N-((S)-1-(((R)-3- methyl-1-((5R,7R)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-269 06 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5R,7R)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-270 07 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5R,7R)-5,6,7- trimethyl-4,8-dioxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-271 08 N-((S)-1-(((R)-3- methyl-1-((5R,7S)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-272 09 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5R,7S)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-273 0 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5R,7S)-5,6,7- trimethyl-4,8-dioxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-274 N-((S)-1-(((R)-3- methyl-1-((5R,7R)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-275 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5R,7R)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-276 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5R,7R)-5,6,7- trimethyl-4,8-dioxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-277 N-((S)-1-(((R)-3- methyl-1-((5R,7S)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-278 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5R,7S)- 5,6,7-trimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-279 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5R,7S)-5,6,7- trimethyl-4,8-dioxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-280 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5- dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-281 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5-dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-282 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5-dioxa-11- aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6 phenylpicolinamide HL-283 0 N-((S)-1-(((R)-3- methyl-1-((1R,7R)-11- methyl-2,6-dioxo-3,5- dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-284 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7R)- 11-methyl-2,6-dioxo- 3,5-dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-285 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7R)-11-methyl- 2,6-dioxo-3,5-dioxa-11- aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-286 N-((S)-1-(((R)-3- methyl-1-((1S,7S)-11- methyl-2,6-dioxo-3,5- dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-287 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1S,7S)-11- methyl-2,6-dioxo-3,5- dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-288 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1S,7S)-11-methyl-2,6- dioxo-3,5-dioxa-11-aza- 4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-289 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5- dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-290 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5-dioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-291 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5-dioxa-11- aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-292 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5,9- trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-293 0 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5,9-trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-294 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5,9-trioxa- 11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-295 N-((S)-1-(((R)-3- methyl-1-((1R,7R)-11- methyl-2,6-dioxo-3,5,9- trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-296 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7R)- 11-methyl-2,6-dioxo- 3,5,9-trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-297 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7R)-11-methyl- 2,6-dioxo-3,5,9-trioxa- 11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-298 N-((S)-1-(((R)-3- methyl-1-((1S,7S)-11- methyl-2,6-dioxo-3,5,9- trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-299 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1S,7S)-11- methyl-2,6-dioxo-3,5,9- trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-300 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1S,7S)-11-methyl-2,6- dioxo-3,5,9-trioxa-11- aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-301 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5,9- trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-302 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5,9-trioxa-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-303 0 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5,9-trioxa- 11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-304 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-305 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5-dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-306 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-307 N-((S)-1-(((R)-3- methyl-1-((1R,7R)-11- methyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-308 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7R)- 11-methyl-2,6-dioxo- 3,5-dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-309 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7R)-11-methyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-310 N-((S)-1-(((R)-3- methyl-1-((1S,7S)-11- methyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-311 2,5-dichloro-N-(2- (((R)-3-methyl-1- ((1S,7S)-11-methyl-2,6- dioxo-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-312 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1S,7S)-11-methyl-2,6- dioxo-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-313 0 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-314 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5-dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-315 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-316 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5- dioxa-9-thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-317 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5-dioxa-9-thia-11-aza- 4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-318 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5-dioxa-9- thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-319 N-((S)-1-(((R)-3- methyl-1-((1S,7S)-11- methyl-2,6-dioxo-3,5- dioxa-9-thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-320 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1S,7S)-11- methyl-2,6-dioxo-3,5- dioxa-9-thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-321 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1S,7S)-11-methyl-2,6- dioxo-3,5-dioxa-9-thia- 11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-322 N-((S)-1-(((R)-3- methyl-1-((1R,7R)-11- methyl-2,6-dioxo-3,5- dioxa-9-thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-323 0 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7R)- 11-methyl-2,6-dioxo- 3,5-dioxa-9-thia-11-aza- 4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-324 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7R)-11-methyl- 2,6-dioxo-3,5-dioxa-9- thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-325 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-3,5- dioxa-9-thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-326 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo- 3,5-dioxa-9-thia-11-aza- 4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-327 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-3,5-dioxa-9- thia-11-aza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-328 N-((S)-1-(((R)-3- methyl-1-((1R,7R)-10- methyl-2,6-dioxo-3,5- dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-329 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7R)- 10-methyl-2,6-dioxo- 3,5-dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-330 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7R)-10-methyl- 2,6-dioxo-3,5-dioxa-10- aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-331 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-10- methyl-2,6-dioxo-3,5- dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-332 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 10-methyl-2,6-dioxo- 3,5-dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-333 0 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-10-methyl- 2,6-dioxo-3,5-dioxa-10- aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-334 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-10- methyl-2,6-dioxo-3,5- dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-335 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 10-methyl-2,6-dioxo- 3,5-dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-336 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-10-methyl- 2,6-dioxo-3,5-dioxa-10- aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-337 N-((S)-1-(((R)-3- methyl-1-((1S,7S)-10- methyl-2,6-dioxo-3,5- dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-338 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1S,7S)-10- methyl-2,6-dioxo-3,5- dioxa-10-aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-339 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-10-methyl- 2,6-dioxo-3,5-dioxa-10- aza-4- borabicyclo[5.2.1]decan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-340 N-((S)-1-(((R)-1- ((1R,7S)-9,11-dimethyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-341 2,5-dichloro-N-(2-(((R)- 1-((1R,7S)-9,11- dimethyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-342 N-((2S,3R)-1-(((R)-1- ((1R,7S)-9,11-dimethyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- an-4-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-343 0 N-((S)-1-(((R)-1- ((1R,7R)-9,11- dimethyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-344 2,5-dichloro-N-(2-(((R)- 1-((1R,7R)-9,11- dimethyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-345 N-((2S,3R)-1-(((R)-1- ((1R,7R)-9,11- dimethyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxo-3- phenylpropan-2-yl)-6- phenylpicolinamide HL-346 N-((S)-1-(((R)-1- ((1S,7S)-9,11-dimethyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-347 2,5-dichloro-N-(2-(((R)- 1-((1S,7S)-9,11- dimethyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-348 N-((2S,3R)-1-(((R)-1- ((1S,7S)-9,11-dimethyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-349 N-((S)-1-(((R)-1- ((1R,7S)-9,11-dimethyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-350 2,5-dichloro-N-(2-(((R)- 1-((1R,7S)-9,11- dimethyl-2,6-dioxo-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-351 N-((2S,3R)-1-(((R)-1- ((1R,7S)-9,11-dimethyl- 2,6-dioxo-3,5-dioxa- 9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-352 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-353 0 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-354 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-9-phenyl-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-355 N-((S)-1-(((R)-3- methyl-1-((1R,7R)-11- methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-356 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7R)- 11-methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-357 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7R)-11-methyl- 2,6-dioxo-9-phenyl-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-358 N-((S)-1-(((R)-3- methyl-1-((1S,7S)-11- methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-359 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1S,7S)-11- methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-360 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1S,7S)-11-methyl-2,6- dioxo-9-phenyl-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-361 N-((S)-1-(((R)-3- methyl-1-((1R,7S)-11- methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-362 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((1R,7S)- 11-methyl-2,6-dioxo-9- phenyl-3,5-dioxa-9,11- diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-2- oxoethyl)benzamide HL-363 00 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((1R,7S)-11-methyl- 2,6-dioxo-9-phenyl-3,5- dioxa-9,11-diaza-4- borabicyclo[5.3.1]undecan- 4-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-364 01 N-((S)-1-(((R)-1-(4,8- dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-365 02 (R)-2,5-dichloro-N-(2- ((1-(4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-366 03 N-((2S,3R)-1-(((R)-1- (4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-367 04 N-((S)-1-(((R)-3- methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-368 05 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-369 06 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-5-methyl-4,8- dioxo-1,3,6,2- trioxaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-370 07 N-((S)-1-(((R)-3- methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-371 08 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-372 09 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-5-methyl-4,8- dioxo-1,3,6,2- trioxaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-373 0 N-((S)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-374 2,5-dichloro-N-(2-(((R)- 1-((5R,7S)-5,7- dimethyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-375 N-((2S,3R)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-376 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-377 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-378 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-379 N-((S)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-380 2,5-dichloro-N-(2-(((R)- 1-((5R,7S)-5,7- dimethyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-381 N-((2S,3R)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-382 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-383 0 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4,8-dioxo- 1,3,6,2-trioxaborocan-2- yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-384 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- trioxaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-385 N-((S)-1-(((R)-1-(4,8- dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-386 (R)-2,5-dichloro-N-(2- ((1-(4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-387 N-((2S,3R)-1-(((R)-1- (4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-388 N-((S)-1-(((R)-3- methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-389 2,5-dichloro-N-((S)-1- (((R)-3-methyl-1-((R)- 5-methyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)benzamide HL-390 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-5-methyl-4,8- dioxo-1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-391 N-((S)-1-(((R)-3- methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-392 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-393 0 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-5-methyl-4,8- dioxo-1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-394 N-((S)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-395 2,5-dichloro-N-(2-(((R)- 1-((5R,7S)-5,7- dimethyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-396 N-((2S,3R)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-397 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-398 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-399 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-400 N-((S)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-401 2,5-dichloro-N-(2-(((R)- 1-((5R,7S)-5,7- dimethyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-402 N-((2S,3R)-1-(((R)-1- ((5R,7S)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-403 0 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-404 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-405 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4,8-dioxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-406 N-((S)-1-(((R)-3- methyl-1-(4-oxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-407 (R)-2,5-dichloro-N-(2- ((3-methyl-1-(4-oxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-408 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1-(4- oxo-1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-409 N-((S)-1-(((R)-3- methyl-1-((R)-7- methyl-4-oxo-1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-410 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-7- methyl-4-oxo-1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-411 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-7-methyl-4-oxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-412 N-((S)-1-(((R)-3- methyl-1-((R)-7- methyl-4-oxo-1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-413 0 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-414 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-5-methyl-4,8- dioxo-1,3,6,2- dioxathiaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-415 N-((S)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-416 2,5-dichloro-N-(2-(((R)- 1-((5S,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-417 N-((2S,3R)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-418 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-419 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-420 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-421 N-((S)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-422 2,5-dichloro-N-(2-(((R)- 1-((5S,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-423 0 N-((2S,3R)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-424 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 1-oxo-3-phenylpropan- 2-yl)pyrazine-2- carboxamide HL-425 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-426 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxathiaborocan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-427 N-((S)-1-(((R)-3- methyl-1-(4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-428 (R)-2,5-dichloro-N-(2- ((3-methyl-1-(4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-2- oxoethyl)benzamide HL-429 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1-(4- oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-430 N-((S)-1-(((R)-3- methyl-1-((R)-7- methyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-431 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-7- methyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-432 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-7-methyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-433 0 N-((S)-1-(((R)-3- methyl-1-((R)-7- methyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-434 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((R)-5- methyl-4,8-dioxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-2- oxoethyl)benzamide HL-435 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((R)-5-methyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-436 N-((S)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-437 2,5-dichloro-N-(2-(((R)- 1-((5S,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-438 N-((2S,3R)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-439 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-440 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-441 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-442 N-((S)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-443 0 2,5-dichloro-N-(2-(((R)- 1-((5S,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-444 N-((2S,3R)-1-(((R)-1- ((5S,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-445 N-((S)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-446 2,5-dichloro-N-(2-(((R)- 1-((5R,7R)-5,7- dimethyl-4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-447 N-((2S,3R)-1-(((R)-1- ((5R,7R)-5,7-dimethyl- 4-oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-448 N-((S)-1-(((R)-3- methyl-1-(6-methyl-4- oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-449 (R)-2,5-dichloro-N-(2- ((3-methyl-1-(6-methyl- 4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-450 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1-(6- methyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-451 N-((S)-1-(((R)-1-((R)- 6,7-dimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-452 2,5-dichloro-N-(2-(((R)- 1-((R)-6,7-dimethyl-4- oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-453 0 N-((2S,3R)-1-(((R)-1- ((R)-6,7-dimethyl-4- oxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-454 N-((S)-1-(((R)-1-((R)- 6,7-dimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-455 2,5-dichloro-N-(2-(((R)- 1-((R)-5,6-dimethyl- 4,8-dioxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-456 N-((2S,3R)-1-(((R)-1- ((R)-5,6-dimethyl-4,8- dioxo-1,3,6,2- dioxazaborocan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-457 N-((S)-1-(((R)-3- methyl-1-((5S,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-458 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5S,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-2- oxoethyl)benzamide HL-459 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5S,7R)-5,6,7- trimethyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-460 N-((S)-1-(((R)-3- methyl-1-((5R,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-461 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5R,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-2- oxoethyl)benzamide HL-462 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5R,7R)-5,6,7- trimethyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-463 00 N-((S)-1-(((R)-3- methyl-1-((5S,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-464 01 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5S,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-2- oxoethyl)benzamide HL-465 02 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5S,7R)-5,6,7- trimethyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-466 03 N-((S)-1-(((R)-3- methyl-1-((5R,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-467 04 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5R,7R)- 5,6,7-trimethyl-4-oxo- 1,3,6,2-dioxazaborocan- 2-yl)butyl)amino)-2- oxoethyl)benzamide HL-468 05 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5R,7R)-5,6,7- trimethyl-4-oxo-1,3,6,2- dioxazaborocan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-469 06 N-((S)-1-(((R)-3- methyl-1-((2R,3R)- 2,3,4-trimethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-470 07 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((2R,3R)- 2,3,4-trimethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)butyl)amino)-2- oxoethyl)benzamide HL-471 08 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((2R,3R)-2,3,4- trimethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-472 09 N-((S)-1-(((R)-3- methyl-1-((2R,3R,5S)- 2,3,4,5-tetramethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-473 0 2,5-dichloro-N-(2-(((R)- 3-methyl-1- ((2R,3R,5S)-2,3,4,5- tetramethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)butyl)amino)-2- oxoethyl)benzamide HL-474 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((2R,3R,5S)-2,3,4,5- tetramethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-475 N-((S)-1-(((R)-1- ((2S,3R,5R)-4-ethyl- 2,3,5-trimethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-476 2,5-dichloro-N-((S)-1- (((R)-1-((2S,3R,5R)-4- ethyl-2,3,5-trimethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)benzamide HL-477 N-((S)-1-(((R)-1- ((2S,3R,5R)-4-ethyl- 2,3,5-trimethyl-6- oxotetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)-6- phenylpicolinamide HL-478 N-((S)-1-(((R)-3- methyl-1-(6-methyl-4,9- dioxo-1,3,6,2- dioxazaboronan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-479 (R)-2,5-dichloro-N-(2- ((3-methyl-1-(6-methyl- 4,9-dioxo-1,3,6,2- dioxazaboronan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-480 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1-(6- methyl-4,9-dioxo- 1,3,6,2-dioxazaboronan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-481 N-((S)-1-(((R)-1-((R)- 5,6-dimethyl-4,9-dioxo- 1,3,6,2-dioxazaboronan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-482 2,5-dichloro-N-(2-(((R)- 1-((R)-5,6-dimethyl- 4,9-dioxo-1,3,6,2- dioxazaboronan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-483 0 N-((2S,3R)-1-(((R)-1- ((R)-5,6-dimethyl-4,9- dioxo-1,3,6,2- dioxazaboronan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-484 N-((S)-1-(((R)-3- methyl-1-((5R,7S)- 5,6,7-trimethyl-4,9- dioxo-1,3,6,2- dioxazaboronan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-485 2,5-dichloro-N-(2-(((R)- 3-methyl-1-((5R,7S)- 5,6,7-trimethyl-4,9- dioxo-1,3,6,2- dioxazaboronan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-486 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1- ((5R,7S)-5,6,7- trimethyl-4,9-dioxo- 1,3,6,2-dioxazaboronan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-487 N-((S)-1-(((R)-1-((R)- 6,8-dimethyl-4,9-dioxo- 1,3,6,2-dioxazaboronan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-488 2,5-dichloro-N-(2-(((R)- 1-((R)-6,8-dimethyl- 4,9-dioxo-1,3,6,2- dioxazaboronan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-489 N-((2S,3R)-1-(((R)-1- ((R)-6,8-dimethyl-4,9- dioxo-1,3,6,2- dioxazaboronan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-490 N-((S)-1-(((R)-1-((S)- 6,7-dimethyl-4,9-dioxo- 1,3,6,2-dioxazaboronan- 2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-491 2,5-dichloro-N-(2-(((R)- 1-((S)-6,7-dimethyl-4,9- dioxo-1,3,6,2- dioxazaboronan-2-yl)- 3-methylbutyl)amino)- 2-oxoethyl)benzamide HL-492 N-((2S,3R)-1-(((R)-1- ((S)-6,7-dimethyl-4,9- dioxo-1,3,6,2- dioxazaboronan-2-yl)- 3-methylbutyl)amino)- 3-hydroxy-1-oxobutan- 2-yl)-6- phenylpicolinamide HL-493 0 N-((S)-1-(((R)-3- methyl-1-(7-methyl- 4,10-dioxo-1,3,7,2- dioxazaborecan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-494 (R)-2,5-dichloro-N-(2- ((3-methyl-1-(7-methyl- 4,10-dioxo-1,3,7,2- dioxazaborecan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-495 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1-(7- methyl-4,10-dioxo- 1,3,7,2-dioxazaborecan- 2-yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-496 N-((S)-1-(((R)-1-((R)- 6,7-dimethyl-4,10- dioxo-1,3,7,2- dioxazaborecan-2-yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-497 2,5-dichloro-N-(2-(((R)- 1-((R)-6,7-dimethyl- 4,10-dioxo-1,3,7,2- dioxazaborecan-2-yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-498 N-((2S,3R)-1-(((R)-1- ((R)-6,7-dimethyl-4,10- dioxo-1,3,7,2- dioxazaborecan-2-yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide HL-499 N-((S)-1-(((R)-3- methyl-1-(7-methyl-4- oxo-1,3,7,2- dioxazaborecan-2- yl)butyl)amino)-1-oxo- 3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-500 (R)-2,5-dichloro-N-(2- ((3-methyl-1-(7-methyl- 4-oxo-1,3,7,2- dioxazaborecan-2- yl)butyl)amino)-2- oxoethyl)benzamide HL-501 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1-(7- methyl-4-oxo-1,3,7,2- dioxazaborecan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-502 N-((S)-1-(((R)-3- methyl-1-(7-methyl- 1,3,7,2-dioxazaborecan- 2-yl)butyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-503 0 (R)-2,5-dichloro-N-(2- ((3-methyl-1-(7-methyl- 1,3,7,2-dioxazaborecan- 2-yl)butyl)amino)-2- oxoethyl)benzamide HL-504 N-((2S,3R)-3-hydroxy- 1-(((R)-3-methyl-1-(7- methyl-1,3,7,2- dioxazaborecan-2- yl)butyl)amino)-1- oxobutan-2-yl)-6- phenylpicolinamide HL-505 N-((S)-1-(((R)-1-(4- ethyltetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)-3- methylbutyl)amino)-1- oxo-3-phenylpropan-2- yl)pyrazine-2- carboxamide HL-506 (R)-2,5-dichloro-N-(2- ((1-(4-ethyltetrahydro- 2H-4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)-3- methylbutyl)amino)-2- oxoethyl)benzamide HL-507 N-((2S,3R)-1-(((R)-1- (4-ethyltetrahydro-2H- 4l4,8l4- [1,3,2]oxazaborolo[2,3- b][1,3,2]oxazaborol-8- yl)-3- methylbutyl)amino)-3- hydroxy-1-oxobutan-2- yl)-6- phenylpicolinamide
Stability Study

(88) Compounds were tested for their stability, under three different conditions (see Table 2), by the following procedures: 1. Room Temperature and Dry: compounds were left at the room temperature (20° C.) under inert dry gas; 2. 30° C. and 65% Humidity: compounds sealed with double bags were put into a stability chamber. Temperature was set at 30° C. while the humidity was controlled at 65%. 3. 37° C. pH=7.4 solution: compounds were dissolved in PBS solution and then the entire solution was submerged under a 37° C. water bath.

(89) TABLE-US-00002 TABLE 2 Stability study of designed chiral specific boron derivatives. Room Temp 30° C./ 37° C. H.sub.2O/ Compound Dry 65% Humidity pH 7.4 HL01-0 − HL01-11 + + + HL01-15 + + + HL01-17 + − Decompose Instant Note: “+” meaning stable, “−” meaning quickly degradable, as determined by RP-HPLC.
Cell Viability Assay
1. Cell Line

(90) The multiple myeloma cell line MM1.S was obtained from the ATCC. Cells were cultured in standard RPMI-1640 media (Hyclone) supplemented with 10% heat-inactivated fetal bovine serum (Gibco), 1% penicillin/streptomycin (Gibco) and grown in a humidified incubator with 5% CO.sub.2 at 37° C.

(91) Eight thousand MM1.S cells per well were seeded in tissue culture-treated 96-well plate (Nunc) and incubated overnight.

(92) 2. Compound Treatment

(93) Eighteen hours after seeding, MM1.S cells were treated with a series of concentrations of five different compounds (Bortezomib, HL01-01, HL01-11, HL01-15, HL1-147) or DMSO vehicle control for 72 hrs in a humidified incubator with 5% CO.sub.2, at 37° C. The concentrations of five different compounds were 0.3, 1, 3.16, 10, 31.6, 100, 316, and 1000 nM. Each well had the same DMSO concentration of 0.05%.

(94) 3. Cell Viability Assay (MTS Assay)

(95) The effects of compounds on cell viability were assessed using CellTiter 96®A Queous One solution Reagent (Promega; G3580).

(96) After being treated with various compounds for 72 hrs, cells in the 96-well plate were centrifuged 1000 rpm for 3 minutes, and 180 ul supernatant were removed from each well. Cells were incubated with 20 ul CellTiter 96®A Queous One solution Reagent and put into incubator with 5% CO.sub.2, at 37° C. for an additional 4 hrs. The absorbance was measured at 490 nm with Automatic Microplate reader (Infinite M1000 pro, Tecan). There was a liner relationship (r.sup.2=0.99) between absorbance and cell number in each plate format. Four sets of experiments for each drug combinations were carried out. Cell viability (Percentage of Cell Survival) was calculated by the following formula: cell viability (%)=(average absorbance of treated group-average absorbance of blank)/(average absorbance of untreated group−average absorbance of blank)×100%. IC50 values were calculated using Prism software.

(97) Results

(98) The cytotoxic effects of compounds including Bortezomib, HL01-11, and HL01-15 on MM1.S cell were assessed using the MTS assay. It was found that all compounds could dose-dependently decrease the cell viability in MM1.S cell. As represented by the cell line assay shown in FIG. 1. Bortezomib and HL01-11 exhibited strong cytotoxic effects on MM1.S cells and both compounds had similar IC.sub.50 values nearly 2 nM. The effect of HL01-15 was weaker than the other compounds. The IC.sub.50 value of HL01-15 was 6.85 nM, as set forth in Table 3:

(99) TABLE-US-00003 TABLE 3 Compound IC.sub.50 (nM) Bortezomib 1.76 HL01-01 1.96 HL01-11 1.62 HL01-15 6.85 HL01-17 (Ixazomib) 9.45

(100) Five compounds exhibited cytotoxicity in MM1.S cells. MM1.S cells were treated with various concentrations of Bortezomib, HL01-11, and HL01-15 for 72 h. Cell viability was assessed using the MTS assay. Mean SEM (n=4).

(101) Although the disclosure has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.