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    • 6. 发明申请
    • EPOTHILONE DERIVATIVES AND METHODS FOR MAKING AND USING THE SAME
    • EPOTHILONE衍生物及其制备和使用方法
    • WO0192255A3
    • 2002-02-28
    • PCT/US0115763
    • 2001-05-15
    • KOSAN BIOSCIENCES INCSANTI DANIELFARDIS MARIAASHLEY GARY
    • SANTI DANIELFARDIS MARIAASHLEY GARY
    • C07D417/06C07D417/14C07D491/04C07D493/04A61K31/335A61P35/00
    • C07D417/06C07D417/14C07D491/04C07D493/04
    • The present invention relates to 16-membered macrocyclic compounds. In one aspect of the present invention, compounds of the formula (I), are provided wherein: R , R , R , and R are each independently hydrogen, methyl or ethyl; R is hydrogen, hydroxyl, oxo, or NRR' where R and R' are independently hydrogen, C1-C10 aliphatic, aryl or alkylaryl; R is hydrogen, oxo, or C1-C10 aliphatic, or optionally R and R together form a carbon-carbon double bond; R is hydrogen, hydroxyl, oxo, C1-C10 aliphatic, C1-C10 alkylester, or halide; R is hydrogen or C1-C10 aliphatic that is optionally substituted C1-C5 aliphatic, C1-C5 alkoxy, aryl, or a functional group selected from the group consisting of acetal, alcohol, aldehyde, amide, amine, carbamate, carboalkoxy, carbonate, carbodiimide, carboxylic acid, dioxolane and halogen, or optionally, R and R together form a 1,3-dioxane that is optionally substituted at the 2-position; R and R are both hydrogen or together form a carbon-carbon double bond or an epoxide; Ar is aryl; and, W is O or NR where R is hydrogen, C1-C10 aliphatic, aryl or alkylaryl provided that at least one of R , R , and R is not hydrogen. These compounds are cytotoxic agents and can be used to treat cancer and non-cancer disorders characterized by cellular hyperproliferation.
    • 本发明涉及16元大环化合物。 在本发明的一个方面,提供式(I)化合物,其中:R 1,R 2,R 3和R 10各自独立地为氢,甲基或乙基; R 4是氢,羟基,氧代或NRR',其中R和R'独立地是氢,C 1 -C 10脂族,芳基或烷基芳基; R 5是氢,氧代或C 1 -C 10脂族基,或任选地R 4和R 5一起形成碳 - 碳双键; R 6是氢,羟基,氧代,C 1 -C 10脂族,C 1 -C 10烷基酯或卤化物; R 7是氢或C 1 -C 10脂族基,其是任选取代的C 1 -C 5脂族,C 1 -C 5烷氧基,芳基或选自缩醛,醇,醛,酰胺,胺,氨基甲酸酯,烷氧羰基的官能团 ,碳酸酯,碳二亚胺,羧酸,二氧戊环和卤素,或任选地,R 6和R 7一起形成任选在2-位取代的1,3-二恶烷; R 8和R 9均为氢或一起形成碳 - 碳双键或环氧化物; Ar为芳基; 并且W是O或NR 11,其中R 11是氢,C 1 -C 10脂族,芳基或烷基芳基,条件是R 4,R 5和R 6中的至少一个不是氢 。 这些化合物是细胞毒性剂,可用于治疗以细胞过度增殖为特征的癌症和非癌症疾病。
    • 7. 发明申请
    • MOTILIDE COMPOUNDS
    • 胶体化合物
    • WO0160833A3
    • 2002-01-24
    • PCT/US0105218
    • 2001-02-15
    • KOSAN BIOSCIENCES INCASHLEY GARYBURLINGAME MARKCARRERAS CHRISTOPHERSANTI DANIEL
    • ASHLEY GARYBURLINGAME MARKCARRERAS CHRISTOPHERSANTI DANIEL
    • A61K31/7048A61P1/00A61P1/04A61P1/10A61P1/14A61P1/16A61P17/00C07H17/08A61K31/70
    • C07H17/08
    • The present invention provides novel macrolide compounds of the formulas (I, II, III or IV) wherein: R is hydroxyl or methoxy; R is selected from the group consisting of hydrogen, hydroxyl, halide, NH2, OR , (a, b, c, and d) where R is C1-C10 alkenyl, C2-C10 alkynyl, aryl or heteroaryl and R and R are each independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, or aryl; R and R are each independently selected from the group consisting of hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl or R and R together form a cycloalkyl or a cycloaryl moiety; R is hydrogen or methyl; R is hydrogen, hydroxyl, oxo, or together with R and the carbons to which they are attached form a cyclic carbonate; R is hydrogen, hydroxyl, OR where R is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, or together with R5 and the carbons to which they are attached form a cyclic carbonate; R7 is methyl, C3-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, alkylaryl, alkenylaryl, alkynylaryl, amidoalkylaryl, amidoalkenylaryl, or amidoalkynylaryl; R is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, alkylaryl, alkenylaryl, alkynylaryl, amidoalkylaryl, amidoalkenylaryl, or amidoalkynylaryl; and, x is a single or a double bond.
    • 本发明提供式(I,II,III或IV)的新型大环内酯化合物,其中:R是羟基或甲氧基; R 1选自氢,羟基,卤素,NH 2,OR 9,(a,b,c和d)其中R 9是C 1 -C 10链烯基,C 2 -C 10炔基, 芳基或杂芳基,R 10和R 11各自独立地为氢,C 1 -C 10烷基,C 2 -C 10烯基,C 2 -C 10炔基或芳基; R 2和R 3各自独立地选自氢,C 1 -C 10烷基,C 2 -C 10烯基,C 2 -C 10炔基,芳基,烷芳基,烯基芳基,炔基芳基或R 2, 3>一起形成环烷基或环芳基部分; R 4是氢或甲基; R 5是氢,羟基,氧代或与R 6一起,并且与它们相连的碳形成环状碳酸酯; R 6是氢,羟基,OR 12,其中R 12是C 1 -C 10烷基,C 2 -C 10烯基,C 2 -C 10炔基,或与R 5一起,并且与它们相连的碳形成环状碳酸酯 ; R 7是甲基,C 3 -C 10烷基,C 2 -C 10烯基,C 2 -C 10炔基,烷基芳基,烯基芳基,炔基芳基,酰氨基烷基芳基,酰胺基烯基芳基或酰胺基炔基芳基; R 8是C 1 -C 10烷基,C 2 -C 10烯基,C 2 -C 10炔基,烷基芳基,烯基芳基,炔基芳基,酰氨基烷基芳基,酰氨基烯基芳基或酰胺基炔基芳基; x是单键或双键。