pyrrolopyrimidine and Stomach-Neoplasms

pyrrolopyrimidine has been researched along with Stomach-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for pyrrolopyrimidine and Stomach-Neoplasms

Article	Year
Design and synthesis of pyrrolo[3,2-d]pyrimidine HER2/EGFR dual inhibitors: improvement of the physicochemical and pharmacokinetic profiles for potent in vivo anti-tumor efficacy. Bioorganic & medicinal chemistry, 2012, Oct-15, Volume: 20, Issue:20 During the course of our studies on a novel HER2/EGFR dual inhibitor (TAK-285), we found an alternative potent pyrrolo[3,2-d]pyrimidine compound (1a). To enhance the pharmacokinetic (PK) profile of this compound, we conducted chemical modifications into its N-5 side chain and conversion of the chemically modified compounds into their salts. Among them, 2cb, the tosylate salt of compound 2c, showed potent HER2/EGFR kinase inhibitory activity (IC(50): 11/11 nM) and cellular growth inhibitory activity (BT-474 cell GI(50): 56 nM) with a good drug metabolism and PK (DMPK) profile. Furthermore, 2cb exhibited significant in vivo antitumor efficacy in both mouse and rat xenograft models with transplanted 4-1ST gastric cancer cell lines (mouse, T/C=0%, 2cb po bid at 100 mg/kg; rat, T/C: -1%, 2cb po bid at 25 mg/kg). Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Design; ErbB Receptors; Half-Life; Humans; Mice; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Rats; Receptor, ErbB-2; Stomach Neoplasms; Sulfones; Transplantation, Heterologous	2012

Article

Year

Design and synthesis of pyrrolo[3,2-d]pyrimidine HER2/EGFR dual inhibitors: improvement of the physicochemical and pharmacokinetic profiles for potent in vivo anti-tumor efficacy.

Bioorganic & medicinal chemistry, 2012, Oct-15, Volume: 20, Issue:20

During the course of our studies on a novel HER2/EGFR dual inhibitor (TAK-285), we found an alternative potent pyrrolo[3,2-d]pyrimidine compound (1a). To enhance the pharmacokinetic (PK) profile of this compound, we conducted chemical modifications into its N-5 side chain and conversion of the chemically modified compounds into their salts. Among them, 2cb, the tosylate salt of compound 2c, showed potent HER2/EGFR kinase inhibitory activity (IC(50): 11/11 nM) and cellular growth inhibitory activity (BT-474 cell GI(50): 56 nM) with a good drug metabolism and PK (DMPK) profile. Furthermore, 2cb exhibited significant in vivo antitumor efficacy in both mouse and rat xenograft models with transplanted 4-1ST gastric cancer cell lines (mouse, T/C=0%, 2cb po bid at 100 mg/kg; rat, T/C: -1%, 2cb po bid at 25 mg/kg).

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Design; ErbB Receptors; Half-Life; Humans; Mice; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Rats; Receptor, ErbB-2; Stomach Neoplasms; Sulfones; Transplantation, Heterologous

2012