- Optimization of imidazole 5-lipoxygenase inhibitors and selection and synthesis of a development candidate
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Structural modification of imidazole 5-lipoxygenase (5-LO) inhibitors for optimizing inhibitory potency, pharmacokinetic behavior and toxicity (ocular) profile led to 4-{3-[4-(2-methyl-1H-imidazol-1-yl)phenylthio]}phenyl-3,4,5,6- tetrahydro-2H-pyran-4-car
- Mano, Takashi,Stevens, Rodney W.,Ando, Kazuo,Kawai, Makoto,Kawamura, Kiyoshi,Nakao, Kazunari,Okumura, Yoshiyuki,Okumura, Takako,Sakakibara, Minoru,Miyamoto, Kimitaka,Tamura, Tetsuya
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p. 965 - 973
(2007/10/03)
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- Imidazole lipoxygenase inhibitors
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PCT No. PCT/IB96/00744 Sec. 371 Date Jun. 29, 1998 Sec. 102(e) Date Jun. 29, 1998 PCT Filed Jul. 24, 1996 PCT Pub. No. WO97/11079 PCT Pub. Date Mar. 27, 1997The present invention provides a compound of formula (I): and a pharmaceutically acceptable salt thereof, wherein Ar is phenylene optionally substituted with halo, hydroxy, cyano, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 halo-substituted alkyl or C1-C4 halo-substituted alkoxy, X is -A-X1- or -X2-A-, where A is a direct bond or C1-C4 alkylene, and X1 is oxy, thio, sulfinyl or sulfonyl; Ar is phenylene, pyridylene or thienylene optionally substituted with halo, hydroxy, cyano, nitro, amino, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 halo-substituted alkyl, C1-C4 halo-substituted alkoxy, C1-C4 alkylamino or di(C1-C4)alkylamino; Y is CN or CONR1R2 wherein R1 and R2 are independently hydrogen or C1-C4 alkyl; and R is hydrogen or C1-C6 alkyl; W is C2-C3 alkylene, one carbon atom of which may be replaced by an oxygen atom. Further the invention provides a pharmaceutical composition for treating an inflammatory disease, allergy or cardiovascular diseases or the like in a mammalian subject which comprises a compound of formula (I) and a pharmaceutically acceptable carrier.
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- 5-lipoxygenase inhibitors
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Novel compounds having the ability to inhibit 5-lipoxygenase enzyme and having the following formula I: STR1 and the pharmaceutically acceptable salts thereof, wherein Ar1 is a heterocyclic moiety which is selected from imidazolyl, pyrrolyl, py
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