CYT997

Lexibulin(CYT-997) is a potent tubulin polymerisation inhibitor with IC50 of 10-100 nM in cancer cell lines; with potent cytotoxic and vascular disrupting activity in vitro and in vivo.IC50 value: 10-100 nM(cell assay) [1]Target: tubulin polymerisation inhibitor in vitro: CYT997 prevented the in vitro polymerization of tubulin with an IC50 of ～3 μmol/L (compared with the half-maximal inhibitory concentration of 2 μmol/L for colchicine under identical conditions) as determined using the c

1-ethyl-3-[2-methoxy-4-[5-methyl-4-[[(1S)-1-(3-pyridinyl)butyl]amino]-2-pyrimidinyl]phenyl]urea is a member of ureas.|Lexibulin is an orally bioavailable small-molecule with tubulin-inhibiting, vascular-disrupting, and potential antineoplastic activities. Lexibulin inhibits tubulin polymerization in tumor blood vessel endothelial cells and tumor cells, blocking the formation of the mitotic spindle and leading to cell cycle arrest at the G2/M phase; this may result in disruption of the tumor vasculature and tumor blood flow, and tumor cell death.

N-Ethyl-N'-[2-methoxy-4-(5-methyl-4-{[(1S)-1-pyridin-3-ylbutyl]amino}pyrimidin-2- yl)phenyl]urea Under a nitrogen atmosphere a mixture of 2-chloro-5-methyl-N-[(1S)-1-pyridin-3- ylbutyl] pyrimidin-4-amine (277 mg, 1.0 mmol) 4-{[(ethylamino) carbonyl] amino}-3- methoxyphenylboronic acid pinacol diester (416 mg, 1.3 mmol), tetrakis (triphenylphosphine) palladium (0) (116 mg, 0.1 mmol) in toluene-n-propanol (12 mL, 3: 1) was treated with 2M aqueous sodium carbonate solution (750 uL, 1.5 mmol). The resulting mixture was stirred vigorously whilst being heated at 100 °C for 17 hours. Once cool ethyl acetate (25 mL) was added and the mixture washed with Ha0 (6 x 15 mL), brine (20 mL) and dried (Na2SO4). Removal of solvent in vacuo then yielded crude product, which was purified by column chromatography using dichloromethane-methanol- aqueous ammonia (93: 7: 1) as eluent to furnish the product (110 mg, 57percent). lH-n. m. r. (CDCl3) 8 0.99 (t, 3H, /=7. 4 Hz, CH3), 1.18 (t, 3H, /= 7.2 Hz, CH3), 1.33-1. 60 (m, 2H, CH2), 1.82-2. 02 (m, 2H, CH2), 2.11 (s, 3H, Ar-Me), 3.25-3. 39 (m, 2H, CH2), 3.87 (s, 3H, OMe), 4. 80-4. 96 (m, 2H, 2 x NH), 5.26-5. 36 (m, 1H, CH), 6.98 (br s, 1H, Ar-NHCONH), 7.22-7. 28 (m, 1H, ArH), 7. 67-7.72 (m, 2H, ArH), 7.83-7. 88 (m, 1H, ArH), 8.05 (d, 1H, J = 0.8 Hz, ArH), 8.10 (d, 1H, J = 8.2 Hz, ArH), 8.47 (dd, 1H, J = 6. 6, 1. 8 Hz, ArH), 8. 69 (d, 1H, j= 2.0 Hz, ArH).N-Ethyl-N'-[2-methoxy-4-(5-methyl-4-{[(1S)-1-pyridin-3-ylbutyl]amino}pyrimidin-2- yl)phenyl]urea Under a nitrogen atmosphere a mixture of 2-chloro-5-methyl-N-[(1S)-1-pyridin-3- ylbutyl] pyrimidin-4-amine (277 mg, 1.0 mmol) 4-{[(ethylamino) carbonyl] amino}-3- methoxyphenylboronic acid pinacol diester (416 mg, 1.3 mmol), tetrakis (triphenylphosphine) palladium (0) (116 mg, 0.1 mmol) in toluene-n-propanol (12 mL, 3: 1) was treated with 2M aqueous sodium carbonate solution (750 uL, 1.5 mmol). The resulting mixture was stirred vigorously whilst being heated at 100 °C for 17 hours. Once cool ethyl acetate (25 mL) was added and the mixture washed with Ha0 (6 x 15 mL), brine (20 mL) and dried (Na2SO4). Removal of solvent in vacuo then yielded crude product, which was purified by column chromatography using dichloromethane-methanol- aqueous ammonia (93: 7: 1) as eluent to furnish the product (110 mg, 57percent). lH-n. m. r. (CDCl3) 8 0.99 (t, 3H, /=7. 4 Hz, CH3), 1.18 (t, 3H, /= 7.2 Hz, CH3), 1.33-1. 60 (m, 2H, CH2), 1.82-2. 02 (m, 2H, CH2), 2.11 (s, 3H, Ar-Me), 3.25-3. 39 (m, 2H, CH2), 3.87 (s, 3H, OMe), 4. 80-4. 96 (m, 2H, 2 x NH), 5.26-5. 36 (m, 1H, CH), 6.98 (br s, 1H, Ar-NHCONH), 7.22-7. 28 (m, 1H, ArH), 7. 67-7.72 (m, 2H, ArH), 7.83-7. 88 (m, 1H, ArH), 8.05 (d, 1H, J = 0.8 Hz, ArH), 8.10 (d, 1H, J = 8.2 Hz, ArH), 8.47 (dd, 1H, J = 6. 6, 1. 8 Hz, ArH), 8. 69 (d, 1H, j= 2.0 Hz, ArH).

Molecular Weight:434.5
XLogP3:3.6
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:9
Exact Mass:434.24302422
Monoisotopic Mass:434.24302422
Topological Polar Surface Area:101
Heavy Atom Count:32
Complexity:565
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes