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    • 87. 发明授权
    • Salts of oxazaphosphorine derivatives
    • 恶唑烷衍生物的盐
    • US4716242A
    • 1987-12-29
    • US704465
    • 1985-02-22
    • Jurgen EngelAxel KleemannUlf NiemeyerPeter HilgardJoerg Pohl
    • Jurgen EngelAxel KleemannUlf NiemeyerPeter HilgardJoerg Pohl
    • C07F9/24A61K31/675A61P35/00A61P35/02C07F9/22C07F9/6584C07F9/40
    • C07F9/65846
    • There are provided new antitumor salts of oxazaphosphorine derivatives of the formula ##STR1## where R.sub.1, R.sub.2, and R.sub.3 are the same or different and represent hydrogen, methyl, ethyl, 2-chloroethyl, or 2-methanesulfonyloxyethyl and wherein at least two of these residues are 2-chloroethyl and/or 2-methanesulfonyl-oxyethyl and A is the group --S--alk--SO.sub.3 H or --N(OH)--CONH--alk--CO.sub.2 H and alk represents a C.sub.2 -C.sub.6 -alkylene residue optionally containing a mercapto group, whereby alk also can be --CH.sub.2 -- in case there is a carboxy group attached to the alk group, with homocysteinethiolactone or .alpha.-amino-.epsilon.-caprolactam or a basic compound of the formula: ##STR2## wherein R.sub.4 is a hydroxy group, an amino group or a C.sub.1 -C.sub.6 -alkoxy group, R.sub.5 is hydrogen or a difluoromethyl group, R.sub.6 is hydrogen, an indolyl-(3)-methyl residue, imidazolyl-(4)-methyl residue, a C.sub.1 -C.sub.10 -alkyl group or a C.sub.1 -C.sub.10 -alkyl group which is substituted by a hydroxy group, a C.sub.1 -C.sub.6 -alkoxy group, a mercapto group, a C.sub.1 -C.sub.6 -alkylmercapto group, a phenyl group, a hydroxy phenyl group, an amino-C.sub.1 -C.sub.6 -alkylmercapto group, an amino-C.sub.1 -C.sub.6 -alkoxy group, an amino group, an aminocarbonyl group, a ureido group (H.sub.2 NCONH--), a guanidino group or a C.sub.1 -C.sub.6 -alkoxycarbonyl group, or wherein R.sub.6 together with the structured portion >CR.sub.5 (NR.sub.7 R.sub.8) forms the proline residue, the 4-hydroxy-proline residue or the 2-oxo-3-amino-3-difluoromethyl-piperidine and the residues R.sub.7 and R.sub.8 represent hydrogen or C.sub.1 -C.sub.6 -alkyl residues.
    • 提供了新的式(ⅩⅧ)的恶唑烷磷衍生物的抗肿瘤盐,其中R 1,R 2和R 3相同或不同,代表氢,甲基,乙基,2-氯乙基或2-甲磺酰氧基乙基,其中这些 残基是2-氯乙基和/或2-甲磺酰氧基乙基,A是-S-烷基-SO 3 H或-N(OH)-CONH-烷基-CO 2 H,烷基代表任选含有巯基的C 2 -C 6亚烷基 其中烷基也可以是-CH 2 - ,如果存在与烷基连接的羧基,具有同半胱氨酸硫内酯或α-氨基 - ε-己内酰胺或下式的碱性化合物:其中R 4是羟基 基团,氨基或C1-C6-烷氧基,R5是氢或二氟甲基,R6是氢,吲哚基 - (3) - 甲基残基,咪唑基 - (4) - 甲基残基,C1-C10- 烷基或被羟基,C1-C6-烷氧基,巯基,C1-C6烷基巯基取代的C1-C10-烷基 基团,苯基,羟基苯基,氨基-C 1 -C 6烷基巯基,氨基-C 1 -C 6烷氧基,氨基,氨基羰基,脲基(H 2 NCONH-),胍基 或C 1 -C 6烷氧基羰基,或其中R 6与结构部分> CR 5(NR 7 R 8)一起形成脯氨酸残基,4-羟基 - 脯氨酸残基或2-氧代-3-氨基-3-二氟甲基 - 哌啶和 残基R7和R8表示氢或C1-C6烷基残基。