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公开(公告)号:US5405990A
公开(公告)日:1995-04-11
申请号:US94952
申请日:1993-07-22
IPC分类号: A61K31/17 , A61K31/195 , A61K31/27 , A61K31/41 , A61K39/395 , A61K45/00 , A61K47/48 , A61P35/00 , A61P43/00 , C07C237/20 , C07C237/40 , C07C269/04 , C07C271/54 , C07C275/24 , C07C275/40 , C07C275/42 , C07C309/66 , C07C309/69 , C07C309/72 , C07C311/51 , C07C317/50 , C07C323/58 , C07D257/04 , C07C261/00 , C07C321/00 , C07F9/02
CPC分类号: C07D257/04 , A61K47/48761 , B82Y5/00 , C07C237/20 , C07C271/54 , C07C275/24 , C07C275/40 , C07C309/66 , C07C311/51
摘要: Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs are substrates for carboxypeptidase G2 (CPG2) and yield more active cytotoxic drugs than known products of CPG2 catalyzed reactions.
摘要翻译: 通用型I的前药被公开用于抗体定向酶前药治疗(ADEPT)。 前药是羧肽酶G2(CPG2)的底物,并且比已知的CPG2催化反应产物产生更多的活性细胞毒性药物。
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公开(公告)号:US5587161A
公开(公告)日:1996-12-24
申请号:US361424
申请日:1994-12-21
IPC分类号: A61K31/17 , A61K31/195 , A61K31/27 , A61K31/41 , A61K39/395 , A61K45/00 , A61K47/48 , A61P35/00 , A61P43/00 , C07C237/20 , C07C237/40 , C07C269/04 , C07C271/54 , C07C275/24 , C07C275/40 , C07C275/42 , C07C309/66 , C07C309/69 , C07C309/72 , C07C311/51 , C07C317/50 , C07C323/58 , C07D257/04 , C07C261/00 , C07F9/02 , C07K16/00
CPC分类号: C07D257/04 , A61K47/48761 , B82Y5/00 , C07C237/20 , C07C271/54 , C07C275/24 , C07C275/40 , C07C309/66 , C07C311/51
摘要: Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs substrates for carboxypeptidase G2 (CPG2) and yield more cytotoxic drugs than known products of CPG2 catalysed
摘要翻译: 通用型I的前药被公开用于抗体定向酶前药治疗(ADEPT)。 用于羧肽酶G2(CPG2)的前体药物底物,并且比已催化的CPG2的产物产生更多的细胞毒性药物
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公开(公告)号:US06852755B1
公开(公告)日:2005-02-08
申请号:US09937714
申请日:2000-03-29
IPC分类号: A61K48/00 , A61K31/606 , A61K31/609 , A61K38/46 , A61K47/48 , A61P35/00 , A61P43/00 , C07C229/60 , C07C237/36 , A61K31/235 , A61K31/255 , C07C229/14 , C07C303/00 , C07C313/00
CPC分类号: B82Y5/00 , A61K47/6899 , A61K47/6957 , C07C229/60 , C07C237/36
摘要: This invention pertains to nitrogen mustard compounds (Formula (II)) and prodrugs therefor (Formula (I)), methods for their preparation, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in therapy and treatment, for example, of cancer, wherein: R1 and R2 are independently —Cl, —Br, —I, —OSO2CH3, or —OSO2Ph; R1a, R2a, R1b, and R2b are independently —H, a C1-4alkyl group, or a C1-4haloalkyl group; R3 is —F, —Cl, —Br, —I, —OCHF2, —C≡CH, —OCF3, —CH3, —CF3, —SF5, —SCF3, or —CF2CF3; R4 is —H or as defined for R3−, R5 is —H or —F; R7 is —H, —C(CH3)3, or —CH2—CH—CH2; Z is —CH2—T—W; T is —CH2—, —O—, —S—, —(S═O)—, or —(SO2)—; W is one of: (1) —COOH; (2)—(C═O)OR8; (3) —(C═O)NR9R9; (4) —SO2NHR10−, (5) SO2OR11; (6)—PO3R11R11; (7) a tetrazol-5-yl group; (8) —CONH—SO2R12; and, (9)-M-Het.
摘要翻译: 本发明涉及氮芥化合物(式(II))及其前药(式(I)),其制备方法,包含这些化合物的药物组合物,以及这些化合物和组合物在体外和体内的用途, 在治疗和治疗中,例如癌症,其中:R 1和R 2独立地是-Cl,-Br,-I,-OSO 2 CH 3或-OSO 2 Ph; R 1a,R 2a,R 1b和R 2b独立地是-H,C 1-4烷基或C 1-4卤代烷基; R 3是-F,-Cl,-Br,-I,-OCHF 2,-C = CH,-OCF 3,-CH 3,-CF 3,-SF 5,-SCF 3或-CF 2 CF 3; R 4是-H或如对R 3-3所定义,R 5是-H或-F; R 7是-H,-C(CH 3)3或-CH 2 -CH-CH 2; Z是-CH 2 -T-W; T是-CH 2 - , - O - , - S - , - (S = O) - 或 - (SO 2) - ; W是以下之一:(1)-COOH; (2) - (C = O)OR 8; (3) - (C = O)NR 9 R 9; (4)-SO 2 NHR 10,(5)SO 2 OR 11; (6)-PO 3 R 11 R 11; (7)四唑-5-基; (8)-CONH-SO 2 R 12; 和(9)-M-Het。
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4.
公开(公告)号:US5811454A
公开(公告)日:1998-09-22
申请号:US537890
申请日:1995-12-21
申请人: Caroline J. Springer
发明人: Caroline J. Springer
IPC分类号: A61K39/395 , A61K31/165 , A61K31/195 , A61K47/48 , A61P35/00 , A61P43/00 , C07C229/60 , C07C231/02 , C07C237/36 , C07C309/73 , A61K31/235 , C07C229/14
CPC分类号: A61K47/48761 , B82Y5/00 , C07C229/60 , C07C237/36
摘要: The invention provides a compound which is a 3-fluorobenzamide of the formula (A) ##STR1## wherein R-NH is the residue of an .alpha.-amino acid R-NH.sub.2 or oligopeptide R-NH.sub.2, and M is a nitrogen mustard group of the formula ##STR2## wherein Y and L, which may be the same or different in a molecule, are leaving groups; or a pharmaceutically acceptable salt thereof. The compounds are useful as prodrugs for treating cancer.
摘要翻译: PCT No.PCT / GB94 / 00941 Sec。 371 1995年12月21日第 102(e)日期1995年12月21日PCT提交1994年5月3日PCT公布。 公开号WO94 / 25429 日本公报1994年11月10日本发明提供了一种化合物,其为式(A)的3-氟苯甲酰胺其中R-NH是α-氨基酸R-NH 2或寡肽R-NH 2的残基, 并且M是式“IMAGE”的氮芥基,其中在分子中可以相同或不同的Y和L是离去基团; 或其药学上可接受的盐。 该化合物可用作治疗癌症的前药。
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公开(公告)号:US5359120A
公开(公告)日:1994-10-25
申请号:US681536
申请日:1991-05-06
申请人: Caroline J. Springer
发明人: Caroline J. Springer
IPC分类号: A61K31/195 , A61K31/215 , A61K38/00 , A61P35/00 , A61P43/00 , C07C237/30 , C07C237/36 , C07C309/65 , C07C309/66 , C07C309/73 , C07K1/113 , C07K5/02 , C07K14/00 , A61K31/165 , A61K31/255
CPC分类号: C07C237/30 , C07C309/66
摘要: The invention provides compounds of the formula XX: M-Ar-CONH-R, where Ar represents an aromatic ring system, R-NH is the residue of an .alpha.-amino acid R-NH.sub.2 or oligopeptide R-NH.sub.2 and contains at least one carboxylic acid group in the form of a tertiary butyl ester and M represents a nitrogen mustard group of formula (a), where Y and L, which may be the same or different in a molecule, are leaving groups. The compounds are useful intermediates for the production of nitrogen mustard prodrugs.
摘要翻译: PCT No.PCT / GB89 / 01042 Sec。 371日期1991年5月6日 102(e)日期1991年5月6日PCT提交1989年9月5日PCT公布。 出版物WO90 / 02729 1990年3月22日。本发明提供式XX化合物:M-Ar-CONH-R,其中Ar表示芳族环系,R-NH是α-氨基酸R-NH 2或寡肽R的残基 -NH 2,并且含有至少一种叔丁酯形式的羧酸基团,M代表式(a)的氮芥基,其中在分子中可以相同或不同的Y和L为离去基团 。 这些化合物是制备氮芥前体药物的有用中间体。
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6.
公开(公告)号:US07235585B2
公开(公告)日:2007-06-26
申请号:US10526173
申请日:2003-09-01
IPC分类号: A01N47/10 , C07C261/00
CPC分类号: B82Y5/00 , A61K47/67 , A61K47/6899 , C07C275/32
摘要: This invention pertains to certain enzyme (CPG2) activated self-immolative nitrogen mustard prodrugs, which are useful in enzyme prodrug therapy (EPT), such as ADEPT and GDEPT, for the treatment of proliferative conditions, such as cancer, and which have the following formula: wherein: RN is independently C1-7alkyl; X1 is independently —I, —Br, or —Cl; X2 is independently —I, —Br, or —Cl; the group —N(CH2CH2X1)(CH2CH2X2) is independently attached at the 2-position or at the 4-position; each RG is independently —H or an ester substituent; n is independently an integer from 0 to 4; each RP, if present, is independently a phenyl substituent; m is independently an integer from 0 to 4; each RM, if present, is independently a mustard substituent; and pharmaceutically acceptable salts, solvates, amides, and esters thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds; such compounds and compositions for use in methods of treatment of the human or animal body by therapy; the use of such compounds and compositions for the manufacture of medicaments for the treatment of proliferative conditions; and the like.
摘要翻译: 本发明涉及可用于酶前体药物治疗(EPT)如ADEPT和GDEPT中用于治疗增殖性疾病如癌症的某些酶(CPG2)活化的自褪色氮芥前药,并且具有以下 式:其中:R N独立地为C 1-7烷基; X 1独立地是-I,-Br或-Cl; X 2独立地是-I,-Br或-Cl; 基团-N(CH 2 CH 2)2 X 1)(CH 2 CH 2) 在2位或4位独立地连接; 每个R“独立地是-H或酯取代基; n独立地为0至4的整数; 如果存在的话,每个R“独立地是苯基取代基; m独立地为0至4的整数; 如果存在的话,每个R“M'独立地是芥子取代基; 和其药学上可接受的盐,溶剂合物,酰胺和酯。 本发明还涉及包含这些化合物的药物组合物; 用于治疗人或动物体的方法中的这种化合物和组合物; 使用这些化合物和组合物来制造用于治疗增殖性病症的药物; 等等。
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公开(公告)号:US5387707A
公开(公告)日:1995-02-07
申请号:US838281
申请日:1992-04-10
申请人: John Mann , Caroline J. Springer
发明人: John Mann , Caroline J. Springer
IPC分类号: C07B61/00 , C07C231/12 , C07C237/36 , C07C303/30 , C07C309/66 , C07C303/00 , C07C309/15
CPC分类号: C07C237/36 , C07C309/66
摘要: 4-[(2-chloroethyl)-(2-hydroxyethyl)-amino]benzoyl amino acids of formula (IV), wherein X represents a group (a), where Pro represents hydrogen or a straight or branched chain C.sub.1-6 alkyl group, and salts thereof, and processes for their production. The compounds are useful for the production of nitrogen mustard prodrugs ##STR1##
摘要翻译: PCT No.PCT / GB90 / 01371 Sec。 371日期:1992年4月10日 102(e)日期1992年4月10日PCT提交1990年9月5日PCT公布。 出版物WO91 / 03460 日期1991年3月21日4 - 式(IV)的[(2-氯乙基) - (2-羟乙基) - 氨基]苯甲酰氨基酸,其中X表示基团(a),其中Pro表示氢或直链或支链 C 1-6烷基及其盐,及其制备方法。 (Ⅳ)化合物可用于制备氮芥芥酸酯前体药物
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