Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 22, 2013, Pages 7025-7037

  Goto, Taiji ^a,b   Shiina, Akiko ^a   Yoshino, Toshiharu ^a   Mizukami, Kiyoshi ^a   Hirahara, Kazuki ^a   Suzuki, Osamu ^a   Sogawa, Yoshitaka ^a   Takahashi, Tomoko ^a   Mikkaichi, Tsuyoshi ^a   Nakao, Naoki ^a   Takahashi, Mizuki ^a   Hasegawa, Masashi ^a   Sasaki, Shigeki ^b  

^a DAIICHI SANKYO CO   (Japan)

^b KYUSHU UNIVERSITY   (Japan)

Author keywords

2 Phenylpyrimidine; cAMP; COPD; Crystallography; PDE4; PDE4 inhibitor; PDE4B

Indexed keywords

2 (DIMETHYLAMINO) 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO]PYRIMIDINE 5 CARBOXAMIDE; 2 [4 [(5 CARBAMOYL 2 PHENYLPYRIMIDIN 4 YL)AMINO]PHENYL]ACETIC ACID; 2 [4 [(5 CARBAMOYL 6 METHYL 2 PHENYLPYRIMIDIN 4 YL)AMINO]PHENYL]ACETIC ACID; 2 [4 [(5 CYANO 6 METHYLSULFANYL 2 PHENYLPYRIMIDIN 4 YL)AMINO]PHENYL]ACETIC ACID; 2 [4 [(5 OXO 2 PHENYL 7,8 DIHYDRO 6H PYRIDO[4,3 D]PYRIMIDIN 4 YL)AMINO]PHENYL]ACETIC ACID; 2 [4 [[5 (DIMETHYLCARBAMOYL) 2 PHENYLPYRIMIDIN 4 YL]AMINO]PHENYL]ACETIC ACID; 2 [4 [[5 (HYDROXYCARBAMOYL) 2 PHENYLPYRIMIDIN 4 YL]AMINO]PHENYL]ACETIC ACID; 2 [4 [[5 (METHYLCARBAMOYL) 2 PHENYLPYRIMIDIN 4 YL]AMINO]PHENYL]ACETIC ACID; 4 [4 (2 AMINO 2 OXO ETHYL)ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO] 2 (1H INDOL 5 YL)PYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO] 2 (3 FURYL)PYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO] 2 (3 PYRIDYL)PYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO] 2 (3 THIENYL)PYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO] 2 ISOPROPENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXO ETHYL]ANILINO] 2 PYRIMIDIN 5 YL PYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (2,2 DIMETHYLPROPYLAMINO) 2 OXOETHYL]ANILINO] 2 (1 PIPERIDYLAMINO)PYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (CYCLOPROPYLMETHYLAMINO) 2 OXO ETHYL]ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (HYDROXYAMINO) 2 OXO ETHYL]ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (ISOBUTYLAMINO) 2 OXO ETHYL]ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (METHANESULFONAMIDO) 2 OXO ETHYL]ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 (TERT BUTYLAMINO) 2 OXO ETHYL]ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 4 [4 [2 OXO 2 (PROPYLAMINO)ETHYL]ANILINO] 2 PHENYLPYRIMIDINE 5 CARBOXAMIDE; 5 CARBAMOYL 2 PHENYLPYRIMIDINE DERIVATIVE; N ISOBUTYL 2 [4 [(5 OXO 2 PHENYL 7,8 DIHYDRO 6H PYRIDO[4,3 D]PYRIMIDIN 4 YL)AMINO]PHENYL]ACETAMIDE; PHOSPHODIESTERASE IV INHIBITOR; PYRIMIDINE DERIVATIVE; ROFLUMILAST; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYTOKINE PRODUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; IN VITRO STUDY; IN VIVO STUDY; LIVER MICROSOME; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NEUTROPHILIA; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; SPLEEN CELL; STRUCTURE ACTIVITY RELATION;

MUS;

2-PHENYLPYRIMIDINE; CAMP; COPD; CRYSTALLOGRAPHY; PDE4; PDE4 INHIBITOR; PDE4B;

ANIMALS; ANTI-INFLAMMATORY AGENTS; BINDING SITES; CATALYTIC DOMAIN; CELLS, CULTURED; CRYSTALLOGRAPHY, X-RAY; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; ENZYME ACTIVATION; HUMANS; LIPOPOLYSACCHARIDES; LUNG DISEASES; MICE; PHOSPHODIESTERASE 4 INHIBITORS; PYRIDONES; PYRIMIDINES; SPLEEN; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84885847217     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2013.09.013     Document Type: Article

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