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    • 8. 发明授权
    • Farnesyl transferase inhibitors, their preparation, the pharmaceutical
compositions which contain them and their use in the preparation of
medicaments
    • 法呢基转移酶抑制剂,它们的制备,含有它们的药物组合物及其在制备药物中的用途
    • US6124465A
    • 2000-09-26
    • US346540
    • 1999-07-02
    • Jean-Dominique BourzatAlain Commer.cedilla.onNorbert DereuPatrick MaillietFabienne Sounigo-ThompsonJean-Paul MartinMarc CapetMichel Cheve
    • Jean-Dominique BourzatAlain Commer.cedilla.onNorbert DereuPatrick MaillietFabienne Sounigo-ThompsonJean-Paul MartinMarc CapetMichel Cheve
    • C07D209/56C07D233/56C07D401/08C07D209/80C07F9/28
    • C07D209/56
    • Novel products of formula (I), their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments. ##STR1## In the formula (I), the following substituents are among the preferred: Ar represents a substituted or condensed phenyl radical or a polycyclic or heterocyclic aromatic radical, R represents a radical of general formula --(CH.sub.2).sub.m --X.sub.1 --(CH.sub.2).sub.n --Z in which X.sub.1 =single bond, O, S; m=0, 1; n=0, 1, 2; it being possible for the CH.sub.2 radicals to be substituted; Z represents carboxyl, COOR.sub.6 (R.sub.6 =alkyl), CON(R.sub.7)(R.sub.8) (R.sub.7 =hydrogen or alkyl and R.sub.8 =hydrogen, hydroxyl, arylsulphonyl, heterocyclyl, optionally substituted amino, optionally substituted alkyloxy or optionally substituted alkyl), PO(OR.sub.9).sub.2 (R.sub.9 =hydrogen or alkyl), an --NH--CO--T (T=hydrogen or optionally substituted alkyl) radical, or else--a ##STR2## radical, R.sub.1 and R.sub.2 =hydrogen or halogen or alkyl, alkyloxy, which is optionally substituted, alkylthio, alkyloxycarbonyl or else R.sub.1 and R.sub.2, at the ortho position with respect to one another, form an optionally substituted heterocycle containing 1 or 2 heteroatoms, R.sub.3 and R.sub.4 =hydrogen or halogen or alkyl, alkenyl, alkyloxy, alkylthio. carboxyl or alkyloxycarbonyl, R.sub.5 =hydrogen, alkyl, alkylthio, X=O or S or --NH--, --CO--, methylene, vinyldiyl, alkene-1,1-diyl or cycloalkane-1,1-diyl, and Y=O or S, in the racemic form, as well as the optical isomers (diastereomers and enantiomers) and the salts of the product of formula (I). The compounds of formula (I) are farnesyl transferase inhibitors which exhibit notable antitumor and antileukemic properties.
    • 式(I)的新产品,其制备方法,含有它们的药物组合物及其在制备药物中的用途。 在式(I)中,以下取代基是优选的:Ar表示取代或稠合的苯基或多环或杂环芳族基,R表示通式 - (CH 2)m -X1(CH 2)n Z 其中X1 =单键,O,S; m = 0,1, n = 0,1,2; CH2基可以被取代; Z代表羧基,COOR6(R6 =烷基),CON(R7)(R8)(R7 =氢或烷基,R8 =氢,羟基,芳基磺酰基,杂环基,任选取代的氨基,任选取代的烷氧基或任选取代的烷基),PO OR 9)2(R 9 =氢或烷基),-NH-CO-T(T =氢或任选取代的烷基)基团,或者 - 基团,R 1和R 2 =氢或卤素或烷基,烷氧基, 取代的烷硫基,烷氧基羰基,或者R1和R2相对于彼此的邻位,形成含有1或2个杂原子的任选取代的杂环,R 3和R 4 =氢或卤素或烷基,烯基,烷氧基,烷硫基。 羧基或烷氧基羰基,R5 =氢,烷基,烷硫基,X = O或S或-NH-,-CO-,亚甲基,乙烯基二烯基,烯-1,1-二基或环烷烃-1,1-二基,Y = O 或S,外消旋形式,以及光学异构体(非对映体和对映体)和式(I)的产物的盐。 式(I)化合物是具有显着的抗肿瘤和抗白血病性质的法呢基转移酶抑制剂。
    • 10. 发明授权
    • Peptide antagonists of neurotensin
    • 神经降压肽的肽拮抗剂
    • US5840682A
    • 1998-11-24
    • US737695
    • 1996-11-19
    • Francois-Frederic ClercMarie-Christine DubroeucqGerard HelynckJean LeboulJean-Paul Martin
    • Francois-Frederic ClercMarie-Christine DubroeucqGerard HelynckJean LeboulJean-Paul Martin
    • C12P21/02A61K38/00A61P1/00A61P1/04A61P9/00A61P11/00A61P25/00A61P25/18A61P25/28A61P35/00A61P37/08C07C27/22C07K5/10C07K7/02C07K7/06C07K7/08C07K7/18C07K14/655C12R1/04A61K38/12
    • C07K14/6555C07C27/22C07K7/02C07K7/083C07K7/18A61K38/00Y02P20/55
    • The invention is directed to a compound of formula ##STR1## in which R represents a hydroxyl, alkyloxy, phenylalkyloxy or --NH--CH.sub.2 --COOH radical, R.sub.1 represents a hydrogen atom, an adamantylacetyl, adamantylcarbonyl, norbornylacetyl, norbornylphenoxycarbonyl, benzoyl, nicotinoyl, 4-phenylbenzoyl, 4-tert-butylbenzoyl or 2-pyrrolidinecarbonyl radical or a protective group for an amine functional group, R.sub.2 represents an Arg or Lys residue, R.sub.3 represents an Arg or Lys residue, R.sub.4 represents a Pro residue, m, n and p, which are the identical or different, represent a number equal to 0 or 1, R.sub.5 and R.sub.6 are identical and represent a hydroxyl or methoxy radical and R.sub.7 represents a hydrogen, chlorine, bromine or iodine atom or a nitro radical, or the compound wherein one or a number of peptide bonds between two amino acid residues are replaced by --CH.sub.2 --NH bonds or the peptide bond between the R.sub.2 and R.sub.3 amino acid residues is replaced by a CH.dbd.CH bond, provided that when R.sub.1 is a hydrogen atom, then the sum of m+n+p is at least equal to 1. The invention is also directed to a pharmaceutical composition comprising the compound of formula I and the preparation of the compound.
    • PCT No.PCT / FR95 / 00643 Sec。 371日期1996年11月19日 102(e)日期1996年11月19日PCT提交1995年5月17日PCT公布。 WO95 / 32218 PCT公开号 日期:1995年11月30日本发明涉及式(I)的化合物,其中R表示羟基,烷氧基,苯基烷氧基或-NH-CH2-COOH基,R1表示氢原子,金刚烷基乙酰基,金刚烷基羰基, 降冰片基乙酰基,降冰片基苯氧基羰基,苯甲酰基,烟酰基,4-苯基苯甲酰基,4-叔丁基苯甲酰基或2-吡咯烷羰基或胺官能团的保护基,R2表示Arg或Lys残基,R3表示Arg或Lys残基,R4表示 相同或不同的Pro残基,m,n和p表示等于0或1的数,R5和R6相同,表示羟基或甲氧基,R7表示氢,氯,溴或碘原子 或硝基,或其中两个氨基酸残基之间的一个或多个肽键被-CH 2 -NH键取代或R2和R3氨基酸残基之间的肽键被CH = CH键取代的化合物, 只要R1是啊 然后m + n + p的总和至少等于1.本发明还涉及包含式I化合物和化合物的制备的药物组合物。