Discovery of novel 2-((pyridin-3-yloxy)methyl)piperazines as α7 nicotinic acetylcholine receptor modulators for the treatment of inflammatory disorders

Journal of Medicinal Chemistry

Volumn 57, Issue 10, 2014, Pages 3966-3983

  Clark, Roger B ^a,b   Lamppu, Diana ^a,c   Libertine, Lyn ^a,d   McDonough, Amy ^a,e   Kumar, Anjali ^a,f   LaRosa, Greg ^a,h   Rush, Roger ^a,g   Elbaum, Daniel ^a,i  

^a Critical Therapeutics Inc   (United States)

^b Tetraphase Pharmaceuticals Inc   (United States)

^c SHIRE   (United States)

^d RXi Pharmaceuticals Corporation   (United States)

^e Bate Biology Carnegie Hall   (United States)

^f Flexion Therapeutics   (United States)

^g Idenix Pharmaceuticals Inc   (United States)

^h PFIZER INC   (United States)

ⁱ DEC Associ LLC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 BIS(TERT BUTOXYCARBONYL)PIPERAZINE 2 CARBOXYLIC ACID; 2 (2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL)OXAZOLO[4,5 B]PYRIDINE; 2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZINE DERIVATIVE; 2 [2 [(PYRIDIN 3 YLOXY)METHYL)PIPERAZIN 1 YL ) 6 [TRIFLUOROMETHOXY]BENZO[D]THIAZOLE; 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL)OXAZOLO[4,5 B]PYRIDINE; 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL] 6 (TRIFLUOROMETHYL)BENZO[D]THIAZOLE; 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]OXAZOLE; 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]THIAZOLE; 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]OXAZOLO[4,5 B]PYRIDINE; 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]THIAZOLO[4,5 B]PYRIDINE; 4 FLUORO 2 [2 [(PYRIDIN 3 YLOXY]METHYL]PIPERAZIN 1 YL)BENZO[D]THIAZOLE; 4,6 DIFLUORO 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]THIAZOLE; 5 BROMO 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL)BENZO[D]OXAZOLE; 5 BROMO 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]OXAZOLE; 5 BROMO 2 [2 [(PYRIDIN 3 YLOXY]METHYL]PIPERAZIN 1 YL)BENZO[D]OXAZOLE; 5 METHOXY 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL)BENZO[D]OXAZOLE; 5 METHOXY 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]THIAZOLE; 6 CHLORO 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]THIAZOLE; 6 CHLORO 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]THIAZOLO[4,5 B]PYRIDINE; 6 FLUORO 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]THIAZOLE; 6 METHOXY 2 (2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL)BENZO[D]THIAZOLE; 6 METHOXY 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL)BENZO[D]OXAZOLE; 6 METHOXY 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]THIAZOLE; 6 METHYL 2 [2 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZIN 1 YL]BENZO[D]THIAZOLE; ANTIINFLAMMATORY AGENT; BUNGAROTOXIN RECEPTOR; PIPERAZINE DERIVATIVE; TERT BUTYL 3 OXOTETRAHYDRO 1H OXAZOLO[3,4 A]PYRAZINE 7 (3H)CARBOXYLATE; TERT BUTYL 3 [(PYRIDIN 3 YLOXY)METHYL]PIPERAZINE 1 CARBOXYLATE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG SAFETY; DRUG SYNTHESIS; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MOUSE; NONHUMAN; PNEUMONIA; RAT; STRUCTURE ACTIVITY RELATION;

ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR; ANIMALS; ANTI-INFLAMMATORY AGENTS; DRUG DISCOVERY; MALE; MICE; MICE, INBRED BALB C; NICOTINIC AGONISTS; PC12 CELLS; PIPERAZINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84901253158     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5004599     Document Type: Article

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