Lomeguatrib

Base Information

• Chemical Name: Lomeguatrib
• CAS No.: 192441-08-0
• Deprecated CAS: 793035-44-6
• Molecular Formula: C10H8BrN5OS
• Molecular Weight: 326.17
• European Community (EC) Number: 803-287-8
• UNII: S79265T71M
• DSSTox Substance ID: DTXSID60172838
• Nikkaji Number: J1.604.400H
• Wikidata: Q27288769
• NCI Thesaurus Code: C66028
• Pharos Ligand ID: SSNXXZ8CT3AY
• ChEMBL ID: CHEMBL339133
• Mol file: 192441-08-0.mol

Synonyms:6-((4-bromo-2-thienyl)methoxy)purin-2-amine;lomeguatrib

Chemical Property of Lomeguatrib

Chemical Property:

• Vapor Pressure: 1.5E-18mmHg at 25°C
• Refractive Index: 1.797
• Boiling Point: 683.8 °C at 760 mmHg
• PKA: 9.42±0.10(Predicted)
• Flash Point: 367.3 °C
• PSA: 117.95000
• Density: 2.07 g/cm³
• LogP: 2.91930
• Storage Temp.: room temp
• Solubility.: DMSO: soluble10mg/mL, clear
• XLogP3: 2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 324.96329
• Heavy Atom Count: 18
• Complexity: 299

Purity/Quality:

98%Min ^*data from raw suppliers

Lomeguatrib ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=C(SC=C1Br)COC2=NC(=NC3=C2NC=N3)N
• Description: Lomeguatrib (192441-08-0) is a potent (IC50?= 9 nM) inhibitor of O6-Methylguanine-DNA Methyltransferase (MGMT), an important DNA repair protein.1?It is currently being investigated in cancers that have acquired resistant to the chemotherapeutic temozolomide2-5, as well as other chemotherapeutics6,7.
• Uses: O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein which removes an alkyl group from the O6 position on guanine in an autoinactivating reaction. Although important in normal DNA repair, this reaction confers resistance to treatments that use O6-alkylating agents to produce cytotoxicity, e.g., in cancer. Lomeguatrib is a modified quanine base which acts as a pseudosubstrate inactivator of MGMT (IC50 = ~3 nM). A non-toxic compound, lomeguatrib completely inactivates MGMT in human prostate and colorectal tumors when given as a single 120 mg oral dose and in primary central nervous system cancers at 160 mg. Lomeguatrib is an inhibitor of O6-methylguanine-DNA methyltransferase (MGMT). Lomeguatrib attenuates MGMT activity in vitro and in vivo. Lomeguatrib enhances the antitumor activity of temozolomide in both human melanoma and MCF-7 xenografts.

Technology Process of Lomeguatrib

There total 2 articles about Lomeguatrib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 70.0%

(4-bromothiophen-2-yl)methanol (79757-77-0) + 2-amino-N,N,N-trimethyl-9H-purine-6-ylammonium chloride (34798-95-3) → 6-((4-bromothiophen-2-yl)methoxy)-9H-purin-2-amine (192441-08-0)

Guidance literature:

(4-bromothiophen-2-yl)methanol; With sodium hydride; dimethyl sulfoxide; for 1h;

2-amino-N,N,N-trimethyl-9H-purine-6-ylammonium chloride; In dimethyl sulfoxide; for 1h; Further stages.;

DOI:10.1021/jm010006e

Reference yield:

4-Bromothiophen-2-aldehyde (18791-75-8) → 6-((4-bromothiophen-2-yl)methoxy)-9H-purin-2-amine (192441-08-0)

Guidance literature:

Multi-step reaction with 2 steps

1.1: 89 percent / NaBH₄ / propan-2-ol / 1 h

2.1: NaH; DMSO / 1 h

2.2: 70 percent / dimethylsulfoxide / 1 h

With sodium tetrahydroborate; sodium hydride; dimethyl sulfoxide; In isopropyl alcohol;

DOI:10.1021/jm010006e

Reference yield: 37.7%

6-((4-bromothiophen-2-yl)methoxy)-9H-purin-2-amine (192441-08-0) + 8-bromooctyl-2,3,4,6-tetra-O-benzoyl-β-D-glucopyranoside (382607-65-0) → 8-[O6-(4-bromothenyl)-guan-9-yl]-octyl-β-D-tetra-O-benzoylglucoside (382607-77-4)

Guidance literature:

6-((4-bromothiophen-2-yl)methoxy)-9H-purin-2-amine; With lithium hydride; In N,N-dimethyl-formamide; at 20 - 80 ℃; for 1h;

8-bromooctyl-2,3,4,6-tetra-O-benzoyl-β-D-glucopyranoside; In N,N-dimethyl-formamide; Further stages.; Heating;

DOI:10.1021/jm010006e

upstream raw materials:

(4-bromothiophen-2-yl)methanol

2-amino-N,N,N-trimethyl-9H-purine-6-ylammonium chloride

4-Bromothiophen-2-aldehyde

Downstream raw materials:

6-[O⁶-(4-bromothenyl)-guan-9-yl]-hexyl-β-D-tetra-O-benzoylglucoside

8-[O⁶-(4-bromothenyl)-guan-9-yl]-octyl-β-D-tetra-O-benzoylglucoside

10-[O⁶-(4-bromothenyl)-guan-9-yl]-decyl-β-D-tetra-O-benzoylglucoside

8-[O⁶-(4-bromothenyl)-guan-9-yl]-octyl-β-D-glucoside

Refernces

• 1、 Reinhard,Hull,Von der Lieth,Eichhorn,Kliem,Kaina,Wiessler. "Monosaccharide-linked inhibitors of O6-methylguanine-DNA methyltransferase (MGMT): Synthesis, molecular modeling, and structure-activity relationships". . p. 4050 - 4061. Retrieved 2007/10/03.