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公开(公告)号:US20050197401A1
公开(公告)日:2005-09-08
申请号:US11044980
申请日:2005-01-27
申请人: Said Sebti , Andrew Hamilton , Rishi Jain
发明人: Said Sebti , Andrew Hamilton , Rishi Jain
IPC分类号: A61K31/195 , A61K47/48 , C07C237/42
CPC分类号: B82Y5/00 , A61K47/54 , A61K47/6949
摘要: Growth factor binding compounds having a plurality of acyclic isophthalic acid groups attached to a non-peptide organic scaffold and pharmaceutical compositions of the same are disclosed. Methods of administering and using the growth factor binding compounds or the growth factor binding compositions are also taught. These novel growth factor binding compounds are useful for treating angiogenesis, excessive cellular proliferation, tumor growth, and a combination thereof as well as inhibiting growth factor binding to cells and phosphorylation.
摘要翻译: 公开了具有连接到非肽有机支架上的多个无环间苯二甲酸基团和其药物组合物的生长因子结合化合物。 还教导了施用和使用生长因子结合化合物或生长因子结合组合物的方法。 这些新的生长因子结合化合物可用于治疗血管发生,过度的细胞增殖,肿瘤生长及其组合以及抑制生长因子结合细胞和磷酸化。
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公开(公告)号:US5965539A
公开(公告)日:1999-10-12
申请号:US584654
申请日:1996-01-11
申请人: Said Sebti , Andrew Hamilton
发明人: Said Sebti , Andrew Hamilton
IPC分类号: A61K38/00 , C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K5/103 , C07K5/107 , A61K38/05
CPC分类号: C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K5/1013 , C07K5/1016 , A61K38/00
摘要: Compounds which inhibit prenyl transferases, particularly farnysyltransferase and geranylgeranyl transferase I, processes for preparing the compounds, pharmaceutical compositions containing the compounds, and methods of use.
摘要翻译: 抑制异戊烯转移酶,特别是法尼基转移酶和香叶基香叶基转移酶I的化合物,制备化合物的方法,含有这些化合物的药物组合物和使用方法。
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公开(公告)号:US5705686A
公开(公告)日:1998-01-06
申请号:US371682
申请日:1995-01-12
申请人: Said Sebti , Andrew Hamilton
发明人: Said Sebti , Andrew Hamilton
IPC分类号: A61K38/00 , C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K5/103 , C07K5/107 , C07K14/54 , C07K14/61 , A61K38/05 , C07C211/00 , C07C321/00
CPC分类号: C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K14/5437 , C07K14/61 , C07K5/1013 , C07K5/1016 , A61K38/00
摘要: A compound of the formula C.sup.1 R where C.sup.1 is 3-mercapto-2-amino-propylamino and R is an aryl group. The compounds are useful for inhibiting p21ras farnesyltransferase.
摘要翻译: 式C1R的化合物,其中C1是3-巯基-2-氨基 - 丙基氨基,R是芳基。 该化合物可用于抑制p21ras法呢基转移酶。
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公开(公告)号:US5602098A
公开(公告)日:1997-02-11
申请号:US62287
申请日:1993-05-18
申请人: Said Sebti , Andrew Hamilton , Churl M. Seong
发明人: Said Sebti , Andrew Hamilton , Churl M. Seong
IPC分类号: A61K38/00 , C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K5/103 , C07K5/107 , C07K14/54 , C07K14/61 , A61K38/06
CPC分类号: C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K14/5437 , C07K14/61 , C07K5/1013 , C07K5/1016 , A61K38/00
摘要: Peptidomimetics of the formula C-AMBA-X where C is cysteine, X is, for example, methionine or phenylalanine and AMBA is a hydrophobic spacer, notably 3-aminomethylbenzoic acid. These compounds are effective inhibitors of p21 ras farnesyltransferase. Other modifications including alternative spacers for AMBA, and replacement of the A.sub.1 A.sub.2 X component of known CA.sub.1 A.sub.2 X tetrapeptides by a non-peptide aryl or heterocyclic component are also disclosed as are various phosphonylated and arylated derivatives of peptides and peptidomimetics. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also referred to.
摘要翻译: 式C-AMBA-X的肽模拟物,其中C是半胱氨酸,X是例如甲硫氨酸或苯丙氨酸,AMBA是疏水间隔物,特别是3-氨基甲基苯甲酸。 这些化合物是p21 ras法呢基转移酶的有效抑制剂。 还公开了包括用于AMBA的替代间隔物和通过非肽芳基或杂环组分置换已知CA1A2X四肽的A1A2X组分的其它修饰物,肽和肽模拟物的各种膦酰化和芳基化衍生物。 还公开了通过功能化肽和肽模拟物的末端氨基和羧酸基团制备的前药。 这种官能化衍生物表现出增加的细胞摄取。 还提及其它结构修饰。
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公开(公告)号:US20080312287A1
公开(公告)日:2008-12-18
申请号:US11886105
申请日:2006-03-17
IPC分类号: A61K31/4439 , C07D403/02 , A61K31/4178 , A61P35/00 , A61P33/06 , C07D401/02
CPC分类号: C07D233/24 , C07D233/42 , C07D401/12 , C07D401/14 , C07D405/14 , C07D409/12 , C07D413/14
摘要: Formula (I): Where R1 is an optionally substituted C3-C12 hydrocarbyl group (preferably a cyclic alkyl group), an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R is a C(O)yR′ group (preferably forming an optionally substituted C2-C5 acyl group), or a S(O)xR′ group, where y is 0 or 1 and x is 0, 1 or 2 and R′ is H or an optionally substituted C1-C12 alkyl group, or R′ is an optionally substituted C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R5, R6, R7, R8, R9 and R10 are each independently selected from H, an optionally substituted C1-C12 hydrocarbyl group, including a C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group, or R5 and R6, R7 and R8 or R9 and R10 together form a keto (C═O) group; RN is H, an optionally substituted C1-C12 hydrocarbyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group, or an optionally substituted heteroaromatic group; A is Formula (II): a Formula (III): group, or a Formula (IV) or Formula (V) group, where Z is N, O or S; Ra is H, a C1-C12 optionally substituted hydrocarbyl group or an optionally substituted aromatic group; n is from 0 to 3; and pharmaceutically acceptable salts thereof. Compounds according to the invention are useful in one or more aspects to inhibit farnesyl transferase, or to treat malaria, neoplasia, a hyperproliferative disease state or arthritis, including rheumaroid arthritis or osteoarthritis.
摘要翻译: 式(I):其中R1是任选取代的C 3 -C 12烃基(优选环状烷基),任选取代的杂环基,任选取代的芳基或任选取代的杂芳基; R是C(O)y R'基团(优选形成任选取代的C 2 -C 5酰基)或S(O)x R'基团,其中y是0或1,x是0,1或2,R' 是H或任选取代的C 1 -C 12烷基,或R'是任选取代的C 5 -C 12环烷基,任选取代的杂环基,任选取代的芳基或任选取代的杂芳基; R5,R6,R7,R8,R9和R10各自独立地选自H,任选取代的C 1 -C 12烃基,包括C 5 -C 12环烷基,任选取代的杂环基,任选取代的芳族基团或任选取代的 杂芳基或R5和R6,R7和R8或R9和R10一起形成酮(CO)基团; RN为H,任选取代的C 1 -C 12烃基,任选取代的杂环基,任选取代的芳族基团或任选取代的杂芳族基团; A是式(II):式(III):基团,或式(IV)或式(V)基团,其中Z是N,O或S; Ra是H,C1-C12任选取代的烃基或任选取代的芳族基团; n为0〜3; 及其药学上可接受的盐。 根据本发明的化合物在一个或多个方面可用于抑制法呢基转移酶或治疗疟疾,瘤形成,过度增生性疾病状态或关节炎,包括风湿性关节炎或骨关节炎。
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公开(公告)号:US20070060521A1
公开(公告)日:2007-03-15
申请号:US11512049
申请日:2006-08-28
申请人: Richard Jove , William Dalton , Said Sebti , Hua Yu , Richard Heller , Mark Jaroszeski , Richard Gilbert , Andrew Hamilton
发明人: Richard Jove , William Dalton , Said Sebti , Hua Yu , Richard Heller , Mark Jaroszeski , Richard Gilbert , Andrew Hamilton
CPC分类号: A61K31/277 , A61K31/00 , A61K31/4155 , A61K31/428 , A61K31/4406 , A61K31/498 , A61K31/517 , A61K38/1709 , A61K38/208 , A61K48/00 , G01N2500/10 , A61K2300/00
摘要: Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.
摘要翻译: 信号转导和转录激活因子(STAT)蛋白具有细胞信号传导的基本作用,并被大量的细胞因子和生长因子激活。 STAT家族STAT3的一个成员在肿瘤发生中起关键作用。 本发明一般涉及STAT3信号通路在人类癌症治疗中的破坏。 STAT3激活显示存在于多种肿瘤细胞系和肿瘤中,以促进肿瘤形成,抑制细胞凋亡,降低对化学治疗剂的敏感性。 抑制STAT3信号传导在肿瘤细胞系中特异性诱导凋亡,并增加对化学治疗剂的敏感性。 本发明更具体地涉及方法,组合物,施用此类组合物的方法,以及鉴定用于抑制STAT3细胞内信号传导治疗人类癌症的组合物的方法。
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公开(公告)号:US20050004009A1
公开(公告)日:2005-01-06
申请号:US10784309
申请日:2004-02-20
申请人: James Turkson , Richard Jove , Said Sebti , Andrew Hamilton
发明人: James Turkson , Richard Jove , Said Sebti , Andrew Hamilton
CPC分类号: C07K7/06 , A61K38/00 , C07K5/06191 , C07K5/0827
摘要: The subject invention concerns compositions and methods for blocking cancer cell growth or proliferation and/or inducing cancer cell death. Compositions of the present invention are peptidomimetics that inhibit STAT function. Peptidomimetics of the invention include compounds of the formula RY*L (where Y* represents phosphotyrosine), with the R group at the Y-1 position. Peptidomimetics of the invention disrupt Stat3 activation and function. Peptidomimetics of the invention significantly inhibit tumor cell growth and induce tumor cell death.
摘要翻译: 本发明涉及用于阻断癌细胞生长或增殖和/或诱导癌细胞死亡的组合物和方法。 本发明的组合物是抑制STAT功能的肽模拟物。 本发明的肽模拟物包括式RY * L(其中Y *表示磷酸酪氨酸)的化合物,其中R基团在Y-1位。 本发明的肽模拟物破坏Stat3的活化和功能。 本发明的肽模拟物显着抑制肿瘤细胞生长并诱导肿瘤细胞死亡。
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公开(公告)号:US6011175A
公开(公告)日:2000-01-04
申请号:US582076
申请日:1996-01-02
申请人: Said Sebti , Andrew Hamilton
发明人: Said Sebti , Andrew Hamilton
IPC分类号: A61K38/00 , C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K5/103 , C07K5/107 , C07K14/54 , C07K14/61 , C07C321/02
CPC分类号: C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K14/5437 , C07K14/61 , C07K5/1013 , C07K5/1016 , A61K38/00
摘要: A compound of the formulaC.sup.0 BwhereinC.sup.0 stands for ##STR1## A representing O or 2H, and R.sub.0 representing SH, NH.sub.2, or C.sub.x H.sub.y --SO.sub.2 --NH--, wherein C.sub.x H.sub.y is a straight chain saturated or unsaturated hydrocarbon, with x being between 1 and 20 and y between 3 and 41, inclusive; andB stands for --NHR, where R is an aryl group.The compounds are useful for inhibiting p21ras farnesyltransferase.
摘要翻译: 式C0B的化合物,其中C0代表A代表O或2H,R 0表示SH,NH 2或C x H y -SO 2 -NH-,其中C x H y是直链饱和或不饱和烃,x在1和20之间,y 3至41岁(含); 而B代表-NHR,其中R是芳基。 该化合物可用于抑制p21ras法呢基转移酶。
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公开(公告)号:US5856310A
公开(公告)日:1999-01-05
申请号:US464203
申请日:1995-06-05
申请人: Said Sebti , Andrew Hamilton , Churl Min Seong
发明人: Said Sebti , Andrew Hamilton , Churl Min Seong
IPC分类号: A61K38/00 , C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K5/103 , C07K5/107 , C07K14/54 , C07K14/61
CPC分类号: C07C323/25 , C07C323/59 , C07C323/60 , C07C329/06 , C07D207/34 , C07D215/38 , C07D217/22 , C07D263/48 , C07D277/38 , C07D307/66 , C07K14/5437 , C07K14/61 , C07K5/1013 , C07K5/1016 , A61K38/00
摘要: Peptidomimetics of the formula C-AMBA-X where C is cysteine, X is, for example, methionine or phenylalanine and AMBA is a hydrophobic spacer, notably 3-aminomethylbenzoic acid. These compounds are effective inhibitors of p21ras farnesyltransferase. Other modifications including alternative spacers for AMBA, and replacement of the A.sub.1 A.sub.2 X component of known CA.sub.1 A.sub.2 X tetrapeptides by a non-peptide aryl or heterocyclic component are also disclosed as are various phosphorylated and arylated derivatives of peptides and peptidomimetics. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also referred to.
摘要翻译: 式C-AMBA-X的肽模拟物,其中C是半胱氨酸,X是例如甲硫氨酸或苯丙氨酸,AMBA是疏水间隔物,特别是3-氨基甲基苯甲酸。 这些化合物是法尼基转移酶p21ras的有效抑制剂。 还公开了包括用于AMBA的替代间隔物和通过非肽芳基或杂环组分置换已知CA1A2X四肽的A1A2X组分的其它修饰物,肽和肽模拟物的各种磷酸化和芳基化衍生物。 还公开了通过功能化肽和肽模拟物的末端氨基和羧酸基团制备的前药。 这种官能化衍生物表现出增加的细胞摄取。 还提及其它结构修饰。
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公开(公告)号:US20060084596A1
公开(公告)日:2006-04-20
申请号:US11226112
申请日:2005-09-14
申请人: Said Sebti , Andrew Hamilton
发明人: Said Sebti , Andrew Hamilton
CPC分类号: C07K7/56 , A61K38/00 , C07K14/001
摘要: Growth factor binding molecules having a plurality of peptide loops attached to a non-peptide organic scaffold, preferably having pseudo-six amino acid peptide loops with four amino acid sidechains. The growth factor binding molecules specifically bind various growth factors and are suitable for treating a subject having tumors or restinosis. In one embodiment a platelet-derived growth factor binding molecule is disclosed that is used to inhibit tumor growth and angiogenesis in solid tumors.
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