934593-90-5

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor composed of a HIF-1α subunit and HIF-1β subunit. Whereas the HIF-1β subunit is constitutively expressed, the HIF-1α subunit is regulated by cellular oxygen levels and therefore plays an important role in maintaining cellular oxygen homeostasis. Under normoxic conditions, HIF-1α is selectively hydroxylated on proline residues 402 and 577 and targeted for destruction by the ubiquitin-proteasome system. Under hypoxic conditions, HIF-1α accumulates and dimerizes with HIF-1β to promote the transcription of a number of genes involved in angiogenesis, glycolysis, growth factor signaling, tumor invasion, and metastasis. CAY10585 is a novel small molecule inhibitor of HIF-1α accumulation and gene transcriptional activity. In a gene reporter assay using human Hep3B and AGS cell lines, CAY10585 prevented HIF-1 transcriptional activity with IC₅₀ values of 2.6 and 0.7 μM, respectively. It blocks HIF-1α accumulation in Hep3B cells in a concentration and time-dependent manner, with complete inhibition at a concentration of 30 μM within 12 hours. CAY10585 also significantly suppresses transcription of the HIF-1 target genes VEGF and erythropoietin at 10 μM.

CAY10585 is a class of hypoxia-inducible factor (HIF-1) responsible for radiation resistance and poor prognosis in cancer therapy.

Synthesis of methyl 3-[2-(4-adamantane-1-yl-phenoxy)-acetamido]-4-hydroxy-benzoate (Cas: 934593-90-5) from 2-(4-(1-adamantane)phenoxy)acetic acid (143.2 mg, 0.5 mmol) and methyl 3-amino-4-hydroxybenzoate (125.4 mg, 0.75 mmol) The general procedure was as follows: first, 2-(4-(1-adamantyl)phenoxy)acetic acid was dissolved in 5 mL of THF, oxalyl chloride (178.5 mg, 0.11 mL, 1.5 mmol) and a catalytic amount of DMF were added. the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. Subsequently, methyl 3-amino-4-hydroxybenzoate and pyridine (0.05 mL) were added and the reaction continued at room temperature. Upon completion of the reaction, extraction was carried out with ethyl acetate and NaCl solution and the organic layer was dried and concentrated with anhydrous MgSO4. The residue was purified by silica gel column chromatography (n-hexane:EtOAc:MeOH = 6:3:1) to afford the target compound (183.2 mg, yield: 84.1%) as a white solid.1H-NMR (DMSO-d6, 300 MHz) δ: 11.10 (1H,s, OH), 9.24 (1H,s, NH), 8.69 (1H, m aromatic-H), 7.60-7.64 (1H, m, aromatic-H), 7.30 (2H, d, J = 8.4 Hz, aromatic-H), 6.94-6.99 (3H, m, aromatic-H), 4.74 (2H, s, CH2), 3.79 (3H, s, CH3), 2.04 (3H, m, adamantane-H), 1.83 (6H, m adamantane-H), 1.72 (6H, m, adamantane-H).

Store at -20°C

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