Discovery of imidazo[1,2- b ]pyridazine derivatives: Selective and orally available Mps1 (TTK) kinase inhibitors exhibiting remarkable antiproliferative activity

Journal of Medicinal Chemistry

Volumn 58, Issue 4, 2015, Pages 1760-1775

  Kusakabe, Ken Ichi ^a   Ide, Nobuyuki ^a   Daigo, Yataro ^b,c   Itoh, Takeshi ^a   Yamamoto, Takahiko ^a   Hashizume, Hiroshi ^a   Nozu, Kohei ^a   Yoshida, Hiroshi ^a   Tadano, Genta ^a   Tagashira, Sachie ^a   Higashino, Kenichi ^a   Okano, Yousuke ^a   Sato, Yuji ^a   Inoue, Makiko ^a   Iguchi, Motofumi ^a   Kanazawa, Takayuki ^a   Ishioka, Yukichi ^a   Dohi, Keiji ^a   Kido, Yasuto ^a   Sakamoto, Shingo ^a   Ando, Shigeru ^a   Maeda, Masahiro ^a   Higaki, Masayo ^a   Baba, Yoshiyasu ^a   Nakamura, Yusuke ^b,d   more..

^a SHIONOGI AND CO LTD   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

^c SHIGA UNIVERSITY OF MEDICAL SCIENCE   (Japan)

^d UNIVERSITY OF CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [6 (4 CYANOPHENYL) 8 [(TETRAHYDRO 2H PYRAN 4 YL)METHYLAMINO]IMIDAZO[1,2 A]PYRAZIN 3 YL] N CYCLOPROPYLBENZAMIDE; 4 [6 (4 CYANOPHENYL) 8 [(TETRAHYDRO 2H PYRAN 4 YL)METHYLAMINO]IMIDAZO[1,2 B]PYRIDAZIN 3 YL] N CYCLOPROPYLBENZAMIDE; 4 [6 (CYCLOHEXYLOXY) 8 [(TETRAHYDRO 2H PYRAN 4 YL)METHYLAMINO]IMIDAZO[1,2 B]PYRIDAZIN 3 YL] N CYCLOPROPYLBENZAMIDE; 4 [6 BROMO 8 [(TETRAHYDRO 2H PYRAN 4 YL)METHYLAMINO]IMIDAZO[1,2 A]PYRAZIN 3 YL] N CYCLOPROPYLBENZAMIDE; 4 [8 (METHYLTHIO)IMIDAZO[1,2 A]PYRAZIN 3 YL]BENZOIC ACID; 6 BROMO 3 IODO N [(TETRAHYDRO 2H PYRAN 4 YL)METHYL]IMIDAZO[1,2 A]PYRAZIN 8 AMINE; 6 CHLORO N [(TETRAHYDRO 2H PYRAN 4 YL)METHYL]IMIDAZO[1,2 B]PYRIDAZIN 8 AMINE; ALISERTIB; ANTINEOPLASTIC AGENT; IMIDAZOLE DERIVATIVE; MONOPOLAR SPINDLE 1 KINASE; N CYCLOPROPYL 4 [8 (ISOBUTYLAMINO)IMIDAZO[1,2 A]PYRAZIN 3 YL]; N CYCLOPROPYL 4 [8 (METHYLSULFONYL)IMIDAZO[1,2 A]PYRAZIN 3 YL]BENZAMIDE; N CYCLOPROPYL 4 [8 [(TETRAHYDRO 2H PYRAN 4 YL)METHYLAMINO] 6 (1,1,1 TRIFLUORO 2 METHYLPROPAN 2 YLAMINO)IMIDAZO[1,2 B]PYRIDAZIN 3 YL]BENZAMIDE; PACLITAXEL; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PYRIDAZINE DERIVATIVE; TERT BUTYL (TETRAHYDRO 2H PYRAN 4 YL)METHYL[6 (1,1,1 TRIFLUORO 2 METHYLPROPAN 2 YLAMINO)IMIDAZO[1,2 B]PYRIDAZIN 8 YL]CARBAMATE; TERT BUTYL 3 IODO 6 (1,1,1 TRIFLUORO 2 METHYLPROPAN 2 YLAMINO)IMIDAZO[1,2 B]PYRIDAZIN 8 YL[(TETRAHYDRO 2H PYRAN 4 YL)METHYL]CARBAMATE; TERT BUTYL 6 (CYCLOHEXYLOXY) 3 IODOIMIDAZO[1,2 B]PYRIDAZIN 8 YL [(TETRAHYDRO 2H PYRAN 4 YL)METHYL]CARBAMATE; TERT BUTYL 6 (CYCLOHEXYLOXY)IMIDAZO[1,2 B]PYRIDAZIN 8 YL [(TETRAHYDRO 2H PYRAN 4 YL)METHYL]CARBAMATE; TERT BUTYL 6 CHLORO 3 IODOIMIDAZO[1,2 B]PYRIDAZIN 8 YL [(TETRAHYDRO 2H PYRAN 4 YL)METHYL]CARBAMATE; TERT BUTYL 6 CHLORO 3 [4 (CYCLOPROPYLCARBAMOYL)PHENYL]IMIDAZO[1,2 B]PYRIDAZIN 8 YL [(TETRAHYDRO 2H PYRAN 4 YL)METHYL]CARBAMATE; TERT BUTYL 6 CHLOROIMIDAZO[1,2 B]PYRIDAZIN 8 YL[(TETRAHYDRO 2H PYRAN 4 YL)METHYL]CARBAMATE; UNCLASSIFIED DRUG; CELL CYCLE PROTEIN; N-CYCLOPROPYL-4-(8-((TETRAHYDRO-2H-PYRAN-4-YL)METHYLAMINO)-6-(1,1,1-TRIFLUORO-2-METHYLPROPAN-2-YLAMINO)IMIDAZO(1,2-B)PYRIDAZIN-3-YL)BENZAMIDE; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; TTK PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER CELL LINE; CANCER INHIBITION; CANCER TISSUE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG DOSE COMPARISON; DRUG PROTEIN BINDING; DRUG SOLUBILITY; FEMALE; HIGH THROUGHPUT SCREENING; IC50; LUNG CANCER; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PLASMA CLEARANCE; RAT; STRUCTURE ACTIVITY RELATION; VOLUME OF DISTRIBUTION AT STEADY-STATE; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; CELL PROLIFERATION; CELL SURVIVAL; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG DEVELOPMENT; DRUG EFFECTS; DRUG SCREENING; HUMAN; METABOLISM; NUDE MOUSE; ORAL DRUG ADMINISTRATION; SYNTHESIS; TUMOR CELL LINE;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; CELL CYCLE PROTEINS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HUMANS; IMIDAZOLES; MICE; MICE, INBRED BALB C; MICE, NUDE; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES; PYRIDAZINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84923886632     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm501599u     Document Type: Article

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