IMINOXYCARBOXYLATES AND DERIVATIVES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS
    1.
    发明申请
    IMINOXYCARBOXYLATES AND DERIVATIVES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS 审中-公开
    作为紫苏酮生物合成酶抑制剂的甲氧基羧酸酯和衍生物

    公开(公告)号:WO1996002507A1

    公开(公告)日:1996-02-01

    申请号:PCT/US1995008367

    申请日:1995-06-28

    Abstract: The present invention relates to a compound of the formula: W-X-Q-Y-CH(R )-O-N=C(R )-A-COM, or a pharmaceutically acceptable salt thereof wherein W is optionally substituted aryl or heteroaryl; X is a valence bond, or methylene, divalent alkylene, alkenylene, alkynylene or alkyloxy; Q is a valence bond, or -O-, -S-, > NR or > NCOR ; Y is optionally substituted phenyl, biphenyl, naphthyl, tetrahydronaphthyl, indolyl, pyridyl, or benzo[b]thienyl, thienyl, thiazolyl, or thiazolylphenyl; R is alkyl, cycloalkyl, alkoxyalkyl, aryl or arylalkyl, heteroaryl or heteroarylalkyl; R is hydrogen, alkyl or hydroxyalkyl; A is a valence bond or is selected from alkylene, alkenylene, alkynylene, cycloalkylene, phenylene, pyridylene, thienylene and furylene; and M is a pharmaceutically acceptable, metabolically cleavable group, -OR , -NR R , -NH-tetrazoyl, -NH-2-, 3-, or 4-pyridyl, and -NH-2-, 4-, or 5-thiazolyl which inhibit leukotriene biosynthesis and are useful in the treatment of inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting lipoxygenase activity and leukotriene biosynthesis.

    Abstract translation: 本发明涉及下式化合物:W-X-Q-Y-CH(R 1)-O-N = C(R 2)-A-COM或其药学上可接受的盐,其中W为任选取代的芳基或杂芳基; X是价键,或亚甲基,二价亚烷基,亚烯基,亚炔基或烷氧基; Q是价键,或-O - , - S-,> NR 4或NCOR 5。 Y是任选取代的苯基,联苯基,萘基,四氢萘基,吲哚基,吡啶基或苯并[b]噻吩基,噻吩基,噻唑基或噻唑基苯基; R 1是烷基,环烷基,烷氧基烷基,芳基或芳基烷基,杂芳基或杂芳基烷基; R 2是氢,烷基或羟烷基; A是价键或选自亚烷基,亚烯基,亚炔基,亚环烷基,亚苯基,亚吡啶基,亚噻吩基和亚芳基; 并且M是药学上可接受的代谢可裂解基团-OR 6,-NR 6 R 7,-NH-三唑基,-NH-2-,3-或4-吡啶基和-NH- 抑制白细胞三烯生物合成的2-,4-或5-噻唑基并且可用于治疗炎性疾病状态。 还公开了白三烯生物合成抑制组合物和抑制脂氧合酶活性和白三烯生物合成的方法。

    BIS-HETEROARYLYLMETHOXYPHENYLKETONE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS
    2.
    发明申请
    BIS-HETEROARYLYLMETHOXYPHENYLKETONE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS 审中-公开
    作为紫苏酮生物合成酶抑制剂的双异氟醚甲基酮衍生物

    公开(公告)号:WO1997012866A1

    公开(公告)日:1997-04-10

    申请号:PCT/US1996015278

    申请日:1996-09-25

    Abstract: Compounds having formula (I) or a pharmaceutically acceptable salt thereof wherein W is selected from the group consisting of optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R and R are one or more groups independently selected from hydrogen, alkyl, haloalkyl, alkoxy, and halogen; Z is selected from the group consisting of N-OH, N-O-A-COM, CH-COM, and CH-CH=N-O-A-COM wherein A is selected from the group consisting of alkylene, alkenylene, cycloalkylene, and optionally substituted alkylphenyl wherein the alkyl portion is of one to six carbon atoms, and M is selected from the group consisting of a pharmaceutically acceptable, metabolically cleavable group, -OR , and -NR R , inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.

    Abstract translation: 具有式(I)化合物或其药学上可接受的盐,其中W选自任选取代的喹啉基,任选取代的苯并噻唑基,任选取代的苯并恶唑基,任选取代的苯并咪唑基,任选取代的喹喔啉基,任选取代的吡啶基,任选取代的嘧啶基,和 任选取代的噻唑基; R 1和R 2是一个或多个独立地选自氢,烷基,卤代烷基,烷氧基和卤素的基团; Z选自N-OH,NOA-COM,CH-COM和CH-CH = NOA-COM,其中A选自亚烷基,亚烯基,亚环烷基和任选取代的烷基苯基,其中烷基 部分为1至6个碳原子,M选自药学上可接受的,代谢可裂解基团-OR 3和-NR 4 R 5,抑制白三烯生物合成,并且可用于 治疗过敏和炎症疾病状态。 还公开了白三烯生物合成抑制组合物和抑制白三烯生物合成的方法。

    SYMMETRICAL BISHETEROARYL-METHOXYPHENYL-IMINOXYALKYL-CARBOXYLATES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS
    3.
    发明申请
    SYMMETRICAL BISHETEROARYL-METHOXYPHENYL-IMINOXYALKYL-CARBOXYLATES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS 审中-公开
    对称双羟基 - 甲氧基苯基 - 甲氧基羰基羧酸酯,它们的制备及其作为紫苏酮生物合成的抑制剂

    公开(公告)号:WO1997012865A1

    公开(公告)日:1997-04-10

    申请号:PCT/US1996015241

    申请日:1996-09-24

    Abstract: Compounds having formula (I) or a pharmaceutically acceptable salt thereof wherein W and Y at each occurrence are the same and W is selected from the group consisting of optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; Y is selected from optionally substituted phenylene and optionally substituted (c) wherein the alkylene portion is of one to six carbon atoms; A is selected from alkylene, alkenylene, cycloalkylene, and optionally substituted (d) wherein the alkylene portion is of one to six carbon atoms: and M is selected from hydrogen, a pharmaceutically acceptable cation, a metabolically cleavable group, -OR , and -NR R , inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis in a mammal.

    Abstract translation: 具有式(I)的化合物或其药学上可接受的盐,其中W和Y在每次出现时相同,W选自任选取代的喹啉基,任选取代的苯并噻唑基,任选取代的苯并恶唑基,任选取代的苯并咪唑基,任选取代的喹喔啉基 ,任选取代的吡啶基,任选取代的嘧啶基和任选取代的噻唑基; Y选自任选取代的亚苯基和任选取代的(c),其中亚烷基部分具有1至6个碳原子; A选自亚烷基,亚烯基,亚环烷基和任选取代的(d),其中亚烷基部分具有1-6个碳原子:M选自氢,可药用阳离子,代谢断裂基团-OR 3 和-NR 4 R 5抑制白三烯生物合成,并且可用于治疗过敏性和炎性疾病状态。 还公开了白三烯生物合成抑制组合物和抑制哺乳动物中白细胞三烯生物合成的方法。

    SYMMETRICAL bis-HETEROARYLMETHOXYPHENYLALKYL CARBOXYLATES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS
    5.
    发明申请
    SYMMETRICAL bis-HETEROARYLMETHOXYPHENYLALKYL CARBOXYLATES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS 审中-公开
    作为紫苏酮生物合成酶抑制剂的对称双 - 二叔丁氧基苯甲醛羧酸酯

    公开(公告)号:WO1997012867A1

    公开(公告)日:1997-04-10

    申请号:PCT/US1996015345

    申请日:1996-09-25

    Abstract: Compounds having formula (I), wherein W is the same at each occurrence and is selected from optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R and R are independently selected from hydrogen, alkyl, haloalkyl, alkoxy, halogen; R is a valence bond or is selected from hydrogen and alkyl; X is a valence bond or is selected from alkylene, alkenylen, and alkynylene; and Z is selected from (a) COM, (b) CH=N-O-A-COM, (c) CH2-O-N=A-COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) -OR , (c) -NR R , (d) -NR SO2R , (e) -NH-Tetrazolyl, and (f) glycinyl inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.

    Abstract translation: 具有式(I)的化合物,其中W在每次出现时相同,并且选自任选取代的喹啉基,任选取代的苯并噻唑基,任选取代的苯并恶唑基,任选取代的苯并咪唑基,任选取代的喹喔啉基,任选取代的吡啶基,任选取代的嘧啶基, 噻唑基; R 1和R 2独立地选自氢,烷基,卤代烷基,烷氧基,卤素; R 3是价键或选自氢和烷基; X是价键或选自亚烷基,烯基和亚炔基; 并且Z选自(a)COM,(b)CH = NOA-COM,(c)CH2-ON = A-COM其中A选自亚烷基和亚环烷基,M选自(a)药学上可接受的代谢 可裂解基团,(b)-OR 6,(c)-NR 7 R 8,(d)-NR 6 SO 2 R 9,(e)-NH-四唑基和(f) 甘氨酰抑制白三烯生物合成,可用于治疗过敏性和炎性疾病状态。 还公开了白三烯生物合成抑制组合物和抑制白三烯生物合成的方法。

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