Novel Hits in the Correction of δf508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein: Synthesis, Pharmacological, and ADME Evaluation of Tetrahydropyrido[4,3-d]pyrimidines for the Potential Treatment of Cystic Fibrosis

Journal of Medicinal Chemistry

Volumn 58, Issue 24, 2015, Pages 9697-9711

  Pesci, Elisabetta ^a,e   Bettinetti, Laura ^a,f   Fanti, Paola ^a,d   Galietta, Luis J V ^b   La Rosa, Salvatore ^a,c   Magnoni, Letizia ^a   Pedemonte, Nicoletta ^b   Sardone, Gian Luca ^a   Maccari, Laura ^a,g  

^a Siena Biotech SpA   (Italy)

^b G GASLINI INSTITUTE   (Italy)

^c Children's Tumor Foundation   (United States)

^d TePe Srl   (Italy)

^e GSK   (Italy)

^f UNIVERSITY OF VERONA   (Italy)

^g Lead Discovery Siena Srl   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

(2 {4 [6 (4 METHOXY BENZYL) 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 YL] PIPERAZIN 1 YL} ETHYL) DIMETHYL AMINE; (6 BENZYL 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) [3 (4 METHYL PIPERAZIN 1 YL) PROPYL] AMINE; (6 BENZYL 2 PYRIDIN 3 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) [3 (4 METHYL PIPERAZIN 1 YL) PROPYL] AMINE; (6 BENZYL 2 PYRIDIN 4 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) [3 (4 METHYLPIPERAZIN 1 YL) PROPYL] AMINE; 1 (6 BENZYL 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERIDIN 3 OL; 1 (6 BENZYL 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERIDINE 4 CARBOXYLIC ACID AMIDE; 1 (6 BENZYL 2 PYRIDIN 3 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERIDINE 4 CARBOXYLIC ACID AMIDE; 2 [4 (6 BENZYL 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERAZIN 1 YL] ACETAMIDE; 2 [4 (6 BENZYL 2 PYRIDIN 3 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERAZIN 1 YL] ACETAMIDE; 4 CHLORO 6 (4 CHLOROBENZYL) 2 PYRIDIN 2 YL 5,6 , 7 , 8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDINE; 4 CHLORO 6 (4 FLUOROBENZYL) 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDINE; 4 CHLORO 6 (4 METHOXYBENZYL) 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDINE; 6 (4 CHLOROBENZYL) 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 OL; 6 (4 FLUOROBENZYL) 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 OL; 6 (4 METHOXYBENZYL) 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 OL; 6 BENZYL 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 OL; 6 BENZYL 2 PYRIDIN 4 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 0L; 6 BENZYL 4 CHLORO 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDINE; 6 BENZYL 4 CHLORO 2 PYRIDIN 3 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDINE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; PYRIMIDINE DERIVATIVE; TETRAHYDROPYRIDO[4,3 D ]PYRIMIDINE; TRIFLUOROMETHANESULFONIC ACID 6 (4 METHOXYBENZYL) 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 YL ESTER; TRIFLUOROMETHANESULFONIC ACID 6 BENZYL 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 YL ESTER; TRIFLUOROMETHANESULFONIC ACID 6 BENZYL 2 PYRIDIN 3 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 YL ESTER; TRIFLUOROMETHANESULFONIC ACID 6 BENZYL 2 PYRIDIN 4 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D]PYRIMIDIN 4 YL ESTER; UNCLASSIFIED DRUG; UNINDEXED DRUG; {2 [4 (6 BENZYL 2 PYRIDIN 2 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERAZIN 1 YL] ETHYL} DIMETHYL AMINE; {2 [4 (6 BENZYL 2 PYRIDIN 3 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERAZIN 1 YL] ETHYL} DIMETHYL AMINE; {2 [4 (6 BENZYL 2 PYRIDIN 4 YL 5,6,7,8 TETRAHYDROPYRIDO[4,3 D] PYRIMIDIN 4 YL) PIPERAZIN 1 YL] ETHYL} DIMETHYL AMINE; ARTIFICIAL MEMBRANE; PYRIDINE DERIVATIVE;

A549 CELL LINE; ARTICLE; CONTROLLED STUDY; CYSTIC FIBROSIS; HUMAN; HUMAN CELL; HYDROGENATION; NUCLEOPHILICITY; PHYSICAL CHEMISTRY; PROTEIN SYNTHESIS; STEREOCHEMISTRY; TREATMENT OUTCOME; ANIMAL; ARTIFICIAL MEMBRANE; CELL LINE; CELL MEMBRANE PERMEABILITY; CHEMISTRY; CYTOLOGY; DOG; GENETICS; LIVER MICROSOME; METABOLISM; MUTATION; RESPIRATORY TRACT MUCOSA; SOLUBILITY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANIMALS; CELL LINE; CELL MEMBRANE PERMEABILITY; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DOGS; HUMANS; MEMBRANES, ARTIFICIAL; MICROSOMES, LIVER; MUTATION; PYRIDINES; PYRIMIDINES; RESPIRATORY MUCOSA; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84953300816     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00771     Document Type: Article

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