6-(Phenylmethoxy)-9H-purin-2-amine

O6-Benzylguanine, a guanine analog, is the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (MGMT/AGT) inhibitor. O6-Benzylguanine acts as an AGT substrate, which transfers its benzyl group to the AGT cysteine residue, thereby irreversibly inactivating AGT and preventing DNA repair. O6-Benzylguanine induces tumor cell apoptosis. Antineoplastic activity[1][2].

6-O-benzylguanine has been used in trials studying the treatment of HIV Infection, Adult Gliosarcoma, Adult Glioblastoma, Stage I Adult Hodgkin Lymphoma, and Stage II Adult Hodgkin Lymphoma, among others.|O6-Benzylguanine is a guanine analogue with antineoplastic activity. O6-benzylguanine binds the DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT), transferring the benzyl moiety to the active-site cysteine and resulting in inhibition of AGT-mediated DNA repair. Co-administration of this agent potentiates the effects of other chemotherapeutic agents that damage DNA. (NCI04)

Benzyl alcohol (37.5 g, 0.347 mol) and sodium hydroxide (2.96 g, 0.074 mol) were mixed and heated, and sodium hydroxide was dissolved. After cooling, 2-amino-6-chloropurine (6.00 g, 0.035 mol) was added, and the reaction was completed by heating and stirring at 80-90 C for 5 hr. Methyl tert- butyl ether (120 ml) was added to the reaction mixture, and the mixture was extracted twice with queous sodium hydroxide solution (70 ml). The obtained aqueous alkali layers were combined, washed with toluene, and after removing toluene, neutralized with 35percent hydrochloric acid to pH 6-8. The precipitated crystals were collected by filtration. The obtained crystals were dried under reduced pressure to give 2- amino-6-benzyloxypurine (7.60 g, 0.032 mol, yield 92percent) as crude crystals.6OBenzylguanine (3). Sodium hydride (1.2 g, 35.4 mmol, 55percent suspension in mineral oil) was added to benzyl alcohol(50 mL) with vigorous stirring under argon. Then, 2amino6chloropurin (2.0 g, 11.8 mmol) was added to the suspensionobtained. The reaction mixture was heated to 60 C and stirredfor 12 h. After cooling, glacial acetic acid (1.4 mL, 24.3 mmol)was added to the suspension. The resulting mixture was extracted with 2 M solution of sodium hydroxide (5×5 mL). The organic phase was diluted with diethyl ether (100 mL) and again extracted with 2 M solution of sodium hydroxide (10×10 mL). Theaqueous layers were combined, washed with diethyl ether(50 mL), glacial acetic acid was added to neutralize the solution(pH 7). Then, the solution was allowed to stand for 12 h at 4 C.A precipitate formed was filtered and washed with water. Afterrecrystallization (ethanol—water (1 : 1)), the crystals were driedin vacuo. The yield was 1.76 g (62percent), yellow crystals, m.p.201—202 C. 1H NMR (DMSOd6, 300 MHz), : 12.25 (br.s, 1 H, N(9)HGua); 7.82 (s, 1 H, C(8)HGua); 7.56—7.21 (m, 5 H, Ph); 6.29 (s, 2 H, NH2Gua); 5.48 (s, 2 H, CH2Ph(Bn)). 13C NMR(DMSOd6, 75 MHz), : 159.7, 159.6, 156.1, 138.5, 136.8, 128.1, 126.5, 112.8, 66.7. Found (percent): C, 56.0; H, 4.8; N, 27.5.C12H11N5O•H2O. Calculated (percent): C, 55.6; H, 5.1; N, 27.0. MS(ESI), found: m/z 243.1033 [M + H]+. C12H12N5O. Calculated:M = 242.1042.General procedure: Sodium or sodium hydride (7-10 mmol) was dissolved inthe appropriate alcohol (5-10 mL). Following the dissolutionand the hydrogen production, 2-amino-6-chloropurine (3) (1-3 mmol) was added and the mixture was refluxed for 4 hthen stirred at room temperature overnight. The reaction was acidified to pH 6 with glacial acetic acid and extracted withdiethylether (3 X 10 mL). The combined organic layers weredried over anhydrous MgSO4, and the solvent was removedunder vacuum. When necessary, the crude product was purifiedwith flash or circular chromatography with a mixture ofdichloromethane/methanol as eluent.2-Amino-6-benzyloxypurine, 10; Benzyl alcohol (37.5 g, 347 mmol) and sodium hydroxide (2.96 g, 74 mmol) were mixed and sodium hydroxide was dissolved on heating at 80°C. After cooling, 2-amino- 6-chloropurine (6.0 g, 35 mmol) was added, and the mixture was heated at 90

An irreversible inhibitor of the mammalian DNA repair protein, O6-alkylguanine-DNA alkyltransferase.Assists in the protection against carcinogenic and therapeutic alkylating agents.

Molecular Weight:241.25
XLogP3:1.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:241.09635999
Monoisotopic Mass:241.09635999
Topological Polar Surface Area:89.7
Heavy Atom Count:18
Complexity:271
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes