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 and Medicinal Chemistry

Volumn 20, Issue 20, 2012, Pages 6171-6180

  Kawakita, Youichi ^a   Miwa, Kazuhiro ^a   Seto, Masaki ^a   Banno, Hiroshi ^a   Ohta, Yoshikazu ^a   Tamura, Toshiya ^a   Yusa, Tadashi ^a   Miki, Hiroshi ^a   Kamiguchi, Hidenori ^a   Ikeda, Yukihiro ^a   Tanaka, Toshimasa ^a   Kamiyama, Keiji ^a   Ishikawa, Tomoyasu ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

EGFR; HER2; Pyrrolo 3,2 d pyrimidine

Indexed keywords

2 (TERT BUTYLSULFONYL) N [2 [4 [[3 CHLORO 4 [3 (TRIFLUOROMETHYL)PHENOXY]PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 (ISOPROPYLSULFONYL)ACETAMIDE; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; N [2 [4 [[3 CHLORO 4 (3 CHLOROPHENOXY)PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 (METHYLSULFONYL)ACETAMIDE; N [2 [4 [[3 CHLORO 4 (3 CHLOROPHENOXY)PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 (METHYLSULFONYL)PROPANAMIDE; N [2 [4 [[3 CHLORO 4 (3 CHLOROPHENOXY)PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 METHYL 2 (METHYLSULFONYL)PROPANAMIDE; N [2 [4 [[3 CHLORO 4 (3 CHLOROPHENOXY)PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 METHYL 2 (METHYLSULFONYL)PROPANAMIDE 4 TOLUENESULFONATE; N [2 [4 [[3 CHLORO 4 (3 CHLOROPHENOXY)PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 METHYL 2 (METHYLSULFONYL)PROPANAMIDE BENZENESULFONATE; N [2 [4 [[3 CHLORO 4 [3 (TRIFLUOROMETHYL)PHENOXY]PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 (ISOPROPYLSULFONYL)ACETAMIDE; N [2 [4 [[3 CHLORO 4 [3 (TRIFLUOROMETHYL)PHENOXY]PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 (METHYLSULFONYL)ACETAMIDE; N [2 [4 [[3 CHLORO 4 [3 (TRIFLUOROMETHYL)PHENOXY]PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 (METHYLSULFONYL)PROPANAMIDE; N [2 [4 [[3 CHLORO 4 [3 (TRIFLUOROMETHYL)PHENOXY]PHENYL]AMINO] 5H PYRROLO[3,2 D]PYRIMIDIN 5 YL]ETHYL] 2 METHYL 2 (METHYLSULFONYL)PROPANAMIDE; TAK 285; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER INHIBITION; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG DESIGN; DRUG EFFICACY; DRUG METABOLISM; DRUG PENETRATION; DRUG POTENCY; DRUG SOLUBILITY; DRUG SYNTHESIS; FEMALE; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALIGNANT NEOPLASTIC DISEASE; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; RAT; STOMACH CANCER; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DRUG DESIGN; HALF-LIFE; HUMANS; MICE; PROTEIN KINASE INHIBITORS; PYRIMIDINES; PYRROLES; RATS; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; STOMACH NEOPLASMS; SULFONES; TRANSPLANTATION, HETEROLOGOUS;

RATTUS;

EID: 84866910818     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.08.002     Document Type: Article

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