Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists.

Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Research Abstract Details 

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Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Abstract Text:

Ippei Sato,Koichiro Morihira,Hiroshi Inami,Hirokazu Kubota,Tatsuaki Morokata,Keiko Suzuki,Noritaka Hamada,Yosuke Iura,Aiko Nitta,Takayuki Imaoka,Toshiya Takahashi,Makoto Takeuchi,Mitsuaki Ohta,Shin-Ichi Tsukamoto,Ippei Sato,Koichiro Morihira,Hiroshi Inami,Hirokazu Kubota,Tatsuaki Morokata,Keiko Suzuki,Noritaka Hamada,Yosuke Iura,Aiko Nitta,Takayuki Imaoka,Toshiya Takahashi,Makoto Takeuchi,Mitsuaki Ohta,Shin-ichi Tsukamoto,Ippei Sato,Koichiro Morihira,Hiroshi Inami,Hirokazu Kubota,Tatsuaki Morokata,Keiko Suzuki,Noritaka Hamada,Yosuke Iura,Aiko Nitta,Takayuki Imaoka,Toshiya Takahashi,Makoto Takeuchi,Mitsuaki Ohta,Shin-ichi Tsukamoto,

A novel class of potent CCR3 receptor antagonists were designed and synthesized starting from N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide (1),which was found by subjecting our chemical library to high throughput screening (HTS). The CCR3 inhibitory activity of the synthesized compounds against eotaxin-induced Ca(2+) influx was evaluated using CCR3-expressing preB cells. Systematic chemical modifications of 1 revealed that the 6-fluoro-2-naphthylmethyl moiety was essential for CCR3 inhibitory activity in this new series of CCR3 antagonists. Further structural modifications of the benzamide and piperidine moieties of 1 led to the identification of N-{8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3- yl}biphenyl-2-carboxamide (31) as a potent CCR3 antagonist with an IC(50) value of 0.020muM.

Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Publishing Authors By Initials

I Sato,K Morihira,H Inami,H Kubota,T Morokata,K Suzuki,N Hamada,Y Iura,A Nitta,T Imaoka,T Takahashi,M Takeuchi,M Ohta,S Tsukamoto,I Sato,K Morihira,H Inami,H Kubota,T Morokata,K Suzuki,N Hamada,Y Iura,A Nitta,T Imaoka,T Takahashi,M Takeuchi,M Ohta,S Tsukamoto,I Sato,K Morihira,H Inami,H Kubota,T Morokata,K Suzuki,N Hamada,Y Iura,A Nitta,T Imaoka,T Takahashi,M Takeuchi,M Ohta,S Tsukamoto,

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Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry

VOLUME: 16

Page Numbers: 144-56

Journal Abbreviation: Bioorg. Med. Chem.

ISSN: 1464-3391

DAY: 5

MONTH: 10

YEAR: 2007

Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Information

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LANGUAGE: eng

NlmUniqueID: 9413298

Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Keywords Mesh Terms:

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Grant and Affiliation Information for Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists.

AFFILIATION: Drug Discovery Research, Astellas Pharma Inc., 21Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.

Country: England

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MEDLINETA: Bioorg Med Chem

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