Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 2, 2003, Pages 277-280

  Stelmach, John E ^a   Liu, Luping ^a   Patel, Sangita B ^a   Pivnichny, James V ^a   Scapin, Giovanna ^a   Singh, Suresh ^a   Hop, Cornelis E C A ^a   Wang, Zhen ^a   Strauss, John R ^a   Cameron, Patricia M ^a   Nichols, Elizabeth A ^a   O'Keefe, Stephen J ^a   O'Neill, Edward A ^a   Schmatz, Dennis M ^a   Schwartz, Cheryl D ^a   Thompson, Chris M ^a   Zaller, Dennis M ^a   Doherty, James B ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 (2,6 DICHLOROPHENYL) 2 (2,4 DIFLUOROPHENYLTHIO)PYRIMIDO[1,6 B]PYRIDAZIN 6 ONE; DIHYDROQUINOLINE DERIVATIVE; IMIDAZOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; ENZYME INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE P38; QUINAZOLINE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BLOOD; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; NONHUMAN; RAT; ANIMAL; AREA UNDER THE CURVE; BIOAVAILABILITY; BIOSYNTHESIS; CHEMICAL STRUCTURE; CONFORMATION; DRUG ANTAGONISM; DRUG EFFECT; IN VITRO STUDY; LIVER MICROSOME; METABOLISM; MONOCYTE; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANIMALS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; DRUG DESIGN; ENZYME INHIBITORS; MICROSOMES, LIVER; MITOGEN-ACTIVATED PROTEIN KINASES; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MONOCYTES; P38 MITOGEN-ACTIVATED PROTEIN KINASES; QUINAZOLINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR NECROSIS FACTOR-ALPHA;

EID: 18744397820     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00752-7     Document Type: Article

References (19)

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17. 3 gave 9s.
18. Analogue 15i was prepared via the Stille coupling of 12c with the corresponding N-t-butyl analogue of 13.
19. HPLC/MS/MS analysis of 15c incubated with rat hepatocytes indicated oxidative N-dealkylation of the piperidine and oxidation/conjugation of the C-5 phenyl and the C-4 benzylic carbon proximal to the urea moiety.