公开(公告)号：US06525074B2

公开(公告)日：2003-02-25

申请号：US09757251

申请日：2001-01-09

Applicant: S. Jane deSolms ,  Suzanne C. MacTough ,  Anthony W. Shaw

Inventor： S. Jane deSolms ,  Suzanne C. MacTough ,  Anthony W. Shaw

IPC: C07D49818

CPC classification number: C07D403/04 ,  C07D413/04 ,  C07D419/04

Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

公开(公告)号：US06316436B1

公开(公告)日：2001-11-13

申请号：US09455627

申请日：1999-12-07

Applicant: S. Jane deSolms ,  Anthony W. Shaw

Inventor： S. Jane deSolms ,  Anthony W. Shaw

IPC: A61K3155

CPC classification number: C07D498/18

Abstract: The present invention is directed to compounds which inhibit prenyl-protein transferase and particularly, the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Abstract translation: 本发明涉及抑制异戊烯基 - 蛋白转移酶，特别是癌基因蛋白Ras的法呢基化的化合物。 本发明还涉及含有本发明化合物的化疗组合物和抑制法呢基蛋白转移酶的方法和癌基因蛋白Ras的法呢基化。

公开(公告)号：US5932590A

公开(公告)日：1999-08-03

申请号：US985337

申请日：1997-12-04

Applicant: Terrence M. Ciccarone ,  S. Jane deSolms

Inventor： Terrence M. Ciccarone ,  S. Jane deSolms

IPC: C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D217/20 ,  A61K31/47

CPC classification number: C07D401/06 ,  C07D401/12 ,  C07D401/14

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

公开(公告)号：US5652257A

公开(公告)日：1997-07-29

申请号：US526244

申请日：1995-09-21

Applicant: Neville J. Anthony ,  S. Jane deSolms ,  Robert P. Gomez ,  Samuel L. Graham ,  John H. Hutchinson ,  Gerald E. Stokker

Inventor： Neville J. Anthony ,  S. Jane deSolms ,  Robert P. Gomez ,  Samuel L. Graham ,  John H. Hutchinson ,  Gerald E. Stokker

IPC: A61K38/00 ,  C07D233/54 ,  C07K5/02 ,  C07K5/06 ,  C07K5/062 ,  A61K31/415 ,  C07D233/02 ,  C07D233/04 ,  C07D233/30

CPC classification number: C07D233/64 ,  C07K5/0205 ,  C07K5/06026 ,  A61K38/00

Abstract: The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogues differ from those previously described as inhibitors of Ras farnesyl transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract translation: 本发明包括通过体内法尼基化修饰的蛋白Ras的CAAX基序的类似物。 这些CAAX类似物抑制Ras的法呢基化。 此外，这些CAAX类似物与先前描述为Ras法呢基转移酶抑制剂的不同之处在于它们不具有硫醇部分。 缺乏硫醇在改善动物药代动力学行为方面提供独特的优势，防止硫醇依赖的化学反应，如快速自身氧化和内源性硫醇形成二硫键，并减少全身毒性。 本发明还包含含有这些法呢基转移酶抑制剂的化疗组合物及其生产方法。

公开(公告)号：US5624936A

公开(公告)日：1997-04-29

申请号：US600792

申请日：1996-02-13

Applicant: S. Jane deSolms

Inventor： S. Jane deSolms

IPC: A61K38/00 ,  C07K5/078 ,  C07D401/06 ,  A61K31/47

CPC classification number: C07K5/06139 ,  A61K38/00

Abstract: The present invention comprises analogs of the CA.sup.1 A.sup.2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA.sup.1 A.sup.2 X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA.sup.1 A.sup.2 X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A.sup.2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract translation: 本发明包括通过体内法尼基化修饰的蛋白Ras的CA1A2X基序的类似物。 这些CA1A2X类似物抑制法呢基蛋白转移酶和某些蛋白质的法呢基化。 此外，这些CA1A2X类似物与先前描述为法呢基 - 蛋白转移酶抑制剂的不同之处在于它们不具有硫醇部分。 缺乏硫醇在改善动物药代动力学行为方面提供独特的优势，防止硫醇依赖的化学反应，如快速自身氧化和内源性硫醇形成二硫键，并减少全身毒性。 本发明的化合物还在基序的A2位置加入环胺部分。 本发明还包含含有这些法呢基转移酶抑制剂的化疗组合物及其生产方法。

公开(公告)号：US06566385B2

公开(公告)日：2003-05-20

申请号：US09757217

申请日：2001-01-09

Applicant: S. Jane deSolms ,  Gerald E. Stokker ,  Anthony W. Shaw

Inventor： S. Jane deSolms ,  Gerald E. Stokker ,  Anthony W. Shaw

IPC: A61K314178

CPC classification number: C07D405/04 ,  C07D413/04

Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

公开(公告)号：US06297239B1

公开(公告)日：2001-10-02

申请号：US09167180

申请日：1998-10-06

Applicant: S. Jane deSolms ,  John H. Hutchinson ,  Anthony W. Shaw ,  Samuel L. Graham ,  Terrence M. Ciccarone

Inventor： S. Jane deSolms ,  John H. Hutchinson ,  Anthony W. Shaw ,  Samuel L. Graham ,  Terrence M. Ciccarone

IPC: A61K314174

CPC classification number: C07D233/64 ,  C07D231/12 ,  C07D233/56 ,  C07D233/90 ,  C07D249/08 ,  C07D401/12

Abstract: The present invention is directed to compounds which inhibit a prenyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting a prenyl-protein transferase and the prenylation of the oncogene protein Ras.

Abstract translation: 本发明涉及抑制异戊烯基 - 蛋白转移酶（FTase）和癌基因蛋白Ras的法呢基化的化合物。 本发明还涉及含有本发明化合物的化学治疗组合物和抑制异戊烯基 - 蛋白质转移酶和致癌基因蛋白Ras的异戊烯基化的方法。

公开(公告)号：US06284755B1

公开(公告)日：2001-09-04

申请号：US09456153

申请日：1999-12-07

Applicant: S. Jane deSolms ,  Samuel L. Graham ,  Anthony W. Shaw ,  Terrence M. Ciccarone ,  Gerald E. Stokker

Inventor： S. Jane deSolms ,  Samuel L. Graham ,  Anthony W. Shaw ,  Terrence M. Ciccarone ,  Gerald E. Stokker

IPC: A01N4346

CPC classification number: C07D233/64 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D471/04

Abstract: The present invention is directed to azepan-2-one compounds which inhibit prenyl-protein transferase, particularly farnesyl-protein transferase (Ftase), and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

Abstract translation: 本发明涉及抑制异戊烯基 - 蛋白质转移酶，特别是法呢基蛋白转移酶（Ftase）的酪蛋白-2-酮化合物和致癌基因蛋白Ras的异戊烯基化。 本发明还涉及含有本发明化合物的化疗组合物和抑制异戊烯基 - 蛋白质转移酶和癌基因蛋白Ras的异戊烯化的方法。

公开(公告)号：US06054466A

公开(公告)日：2000-04-25

申请号：US195578

申请日：1998-11-18

Applicant: Terrence M. Ciccarone ,  S. Jane deSolms

Inventor： Terrence M. Ciccarone ,  S. Jane deSolms

IPC: C07D471/04 ,  A61K31/435

CPC classification number: C07D471/04

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

公开(公告)号：US5939439A

公开(公告)日：1999-08-17

申请号：US995744

申请日：1997-12-22

Applicant: Neville J. Anthony ,  Samuel L. Graham ,  Lekhanh O. Tran ,  Ian M. Bell ,  S. Jane deSolms ,  Robert P. Gomez ,  Michelle Sparks Kuo ,  William C. Lumma, Jr. ,  Debra S. Perlow ,  Anthony W. Shaw ,  John S. Wai ,  Steven D. Young

Inventor： Neville J. Anthony ,  Samuel L. Graham ,  Lekhanh O. Tran ,  Ian M. Bell ,  S. Jane deSolms ,  Robert P. Gomez ,  Michelle Sparks Kuo ,  William C. Lumma, Jr. ,  Debra S. Perlow ,  Anthony W. Shaw ,  John S. Wai ,  Steven D. Young

IPC: C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D417/14 ,  C07D471/04 ,  C07D401/04 ,  A61K31/44

CPC classification number: C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D417/14 ,  C07D471/04

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.