公开(公告)号：US07435737B2

公开(公告)日：2008-10-14

申请号：US11635319

申请日：2006-12-07

Applicant: Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

Inventor： Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

IPC: A61K31/496

CPC classification number: C07D401/12 ,  C07D215/42 ,  C07D215/54 ,  C07D405/12 ,  C07D409/12

Abstract: Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

公开(公告)号：US07238809B2

公开(公告)日：2007-07-03

申请号：US11415842

申请日：2006-05-02

Applicant: Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

Inventor： Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

IPC: C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

CPC classification number: C07D401/12 ,  C07D215/42 ,  C07D215/54 ,  C07D405/12 ,  C07D409/12

Abstract: Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

公开(公告)号：US5936065A

公开(公告)日：1999-08-10

申请号：US462424

申请日：1995-06-05

Applicant: Thomas S. Arrhenius ,  Mariano J. Elices ,  Federico C. A. Gaeta

Inventor： Thomas S. Arrhenius ,  Mariano J. Elices ,  Federico C. A. Gaeta

IPC: A61K38/00 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  A61P11/00 ,  A61P17/00 ,  A61P25/00 ,  A61P29/00 ,  C07K5/02 ,  C07K5/06 ,  C07K5/072 ,  C07K5/08 ,  C07K5/083 ,  C07K5/087 ,  C07K5/09 ,  C07K5/093 ,  C07K5/097 ,  C07K5/10 ,  C07K5/103 ,  C07K5/107 ,  C07K5/11 ,  C07K7/06 ,  C07K14/78

CPC classification number: C07K7/06 ,  C07K14/78 ,  C07K5/0205 ,  C07K5/0207 ,  C07K5/021 ,  C07K5/06034 ,  C07K5/06113 ,  C07K5/0804 ,  C07K5/0808 ,  C07K5/081 ,  C07K5/0812 ,  C07K5/0815 ,  C07K5/0819 ,  C07K5/0821 ,  C07K5/1005 ,  C07K5/1008 ,  C07K5/101 ,  C07K5/1013 ,  C07K5/1016 ,  C07K5/1019 ,  A61K38/00

Abstract: The present invention contemplates a compound defined by the following formula: ##STR1## that inhibits the binding between the VLA-4 and the fibronectin CS-1 compound. Pharmaceutical compositions containing a contemplated compound and methods for treating immunoinflammatory conditions using the compound are also disclosed.

Abstract translation: 本发明考虑由下式限定的化合物：其抑制VLA-4与纤连蛋白CS-1化合物之间的结合。 还公开了含有预期化合物的药物组合物和使用该化合物治疗免疫炎性病症的方法。

公开(公告)号：US5656638A

公开(公告)日：1997-08-12

申请号：US554788

申请日：1995-11-07

Applicant: Federico C. A. Gaeta ,  Elaine C. Stracker ,  Patricia A. Peterli-Roth

Inventor： Federico C. A. Gaeta ,  Elaine C. Stracker ,  Patricia A. Peterli-Roth

IPC: C07D333/70 ,  C07D495/04 ,  A61K31/38

CPC classification number: C07D333/70 ,  C07D495/04

Abstract: Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds characterized by the following structure: ##STR1## and its pharmaceutically acceptable salts. Z is selected from the group consisting of oxygen, sulfur, sulfone, sulfinyl and --NR--, where R selected from the group consisting of hydrogen, alkyl, aryl, and aralkyl. R.sub.1 is --Y.sub.n R.sub.6, where n is an integer between 0 and 10 and each Y.sub.n for n greater than 0 independently is methylene, methine, or quaternary carbon, and R.sub.6, for any value of n, is alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, alkylcarbonyl, arylcarbonyl, heteroalkylcarbonyl, heteroaralkylcarbonyl, aralkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, or arylsulfinyl. R.sub.2 is hydrogen, alkyl, aryl, hydroxyl, alkoxyl, aryloxyl, halogen, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl, or arylsulfonyl. R.sub.3 and R.sub.4 are selected independently from the group consisting of hydrogen, amino, alkylamino, arylamino, heterocycleamino, aralkylamino, heterocylcealkylamino, dialkylamino, diarylamino, arylalkylamino, nitro, halogen, hydroxyl, aryloxyl, alkoxyl, lower alkyl, aryl, heteroaryl, aralkyl, cyano, carboxyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, and heteroaralkyl. Finally, R.sub.5 is selected from the group consisting of iminyl, hydroximinyl, alkyliminyl, aryliminyl, aralkyliminyl, alkoximinyl, aryloximinyl, heterocycleiminyl, cyclic iminyl, bis(alkylthio)methyl, bis(arylthio)methyl, bis(alkoxy)methyl, bis(aryloxy)methyl, carboxaldehyde, hydroxymethyl, alkoxymethyl, aryloxymethyl, aralkoxymethyl, heterocycleoxymethyl, heterocyclealkoxymethyl, and --HC.dbd.NNHR.sub.7 where R.sub.7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heterocycle, heterocyclealkyl, and --C(.dbd.X.sub.1)(X.sub.2).sub.p R.sub.8 where p is 0 or 1, X.sub.1 is oxygen or sulfur, X.sub.2 is selected from the group consisting of oxygen, sulfur, and --NR.sub.9 --, where R.sub.8 and R.sub.9 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, and heterocycle.

公开(公告)号：US07824849B2

公开(公告)日：2010-11-02

申请号：US11413838

申请日：2006-04-27

Applicant: Federico C. A. Gaeta

Inventor： Federico C. A. Gaeta

IPC: C12Q1/00

CPC classification number: C12N9/1241 ,  A61K38/00 ,  A61K39/0011 ,  A61K2039/5154 ,  A61K2039/5158 ,  A61K2039/55522 ,  C12N9/1276

Abstract: The invention provides dendritic cell (DC) preparations that present a telomerase reverse transcriptase (TRT) peptide in the context of an MHC class I or MHC class II molecule. The DCs may be pulsed with a TRT polypeptide, or may comprise a recombinant polynucleotide encoding TRT. The invention also describes the use of such compositions for the prevention and treatment of cancers and other diseases.

Abstract translation: 本发明提供了在MHC I类或II类分子的上下文中提供端粒酶逆转录酶（TRT）肽的树突状细胞（DC）制剂。 DC可以用TRT多肽脉冲，或者可以包含编码TRT的重组多核苷酸。 本发明还描述了这种组合物用于预防和治疗癌症和其它疾病的用途。

公开(公告)号：US07514225B2

公开(公告)日：2009-04-07

申请号：US11182360

申请日：2005-07-15

Applicant: Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

Inventor： Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

IPC: G01N33/53 ,  C12N5/00 ,  C07K16/24 ,  C07K14/52

CPC classification number: C07D401/12 ,  C07D215/42 ,  C07D215/54 ,  C07D405/12 ,  C07D409/12

Abstract: Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

Abstract translation: 提供了MIF的抑制剂，其可用于治疗各种疾病，包括治疗与MIF活性相关的病理状况。 MIF的抑制剂具有以下结构：包括其立体异构体，前药和药学上可接受的盐，其中n，R 1，R 2，R 3，R 4，X，Y和Z如本文所定义。 还提供了含有与药学上可接受的载体组合的MIF抑制剂的组合物，以及使用该组合物的方法。

公开(公告)号：US07432374B2

公开(公告)日：2008-10-07

申请号：US11687611

申请日：2007-03-16

Applicant: Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

Inventor： Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

IPC: C07D215/42 ,  C07D215/54 ,  C07D401/06 ,  C07D403/06

CPC classification number: C07D401/12 ,  C07D215/42 ,  C07D215/54 ,  C07D405/12 ,  C07D409/12

Abstract: Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

Abstract translation: 提供了MIF的抑制剂，其可用于治疗各种疾病，包括治疗与MIF活性相关的病理状况。 MIF的抑制剂具有以下结构：包括其立体异构体，前药和药学上可接受的盐，其中n，R 1，R 2，R 3， >，R 4，X，Y和Z如本文所定义。 还提供了含有与药学上可接受的载体组合的MIF抑制剂的组合物，以及使用该组合物的方法。

公开(公告)号：US07202248B2

公开(公告)日：2007-04-10

申请号：US11344938

申请日：2006-01-31

Applicant: Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

Inventor： Federico C. A. Gaeta ,  Andrew Baird ,  Jerry Anchin ,  Wenbin Ying ,  Robert Florkiewicz ,  Jagadish Sircar ,  Sunil Kumar K. C.

IPC: A61K31/496

CPC classification number: C07D401/12 ,  C07D215/42 ,  C07D215/54 ,  C07D405/12 ,  C07D409/12

Abstract: Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

Abstract translation: 提供了MIF的抑制剂，其可用于治疗各种疾病，包括治疗与MIF活性相关的病理状况。 MIF的抑制剂具有以下结构：

公开(公告)号：US5703116A

公开(公告)日：1997-12-30

申请号：US424813

申请日：1995-04-18

Applicant: Federico C. A. Gaeta ,  Adam Antoni Galan ,  Elaine C. Stracker

Inventor： Federico C. A. Gaeta ,  Adam Antoni Galan ,  Elaine C. Stracker

IPC: C07D495/04 ,  A61K31/38 ,  C07D333/56

CPC classification number: C07D495/04

Abstract: Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds that are derivatives of benzo�b!thiophenes. Such compounds are characterized by the following structure: ##STR1## In this compound, R.sub.1 is selected from the group consisting of --OR.sub.7, --NR.sub.8 R.sub.9, --NHNR.sub.10 R.sub.11, --NHNHC(X.sub.2)NHR.sub.12, --NHSO.sub.2 NR.sub.8 R.sub.9, --NHNHC(O)R.sub.12, --NHNHSO.sub.2 R.sub.12 and --NHC(O)NR.sub.8 R.sub.9. R.sub.7 -R.sub.12 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl and heteroaralkyl. X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen and sulfur. R.sub.2 is hydrogen or halogen. R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, --NR.sub.8 R.sub.9, nitro, cyano, alkoxyl, lower alkyl, aryl and aryloxyl.

Abstract translation: 用于治疗癌症和其它疾病的方法和组合物，其中端粒酶活性的抑制可以改善疾病症状或预防或治疗该疾病涉及作为苯并[b]噻吩衍生物的化合物。 这种化合物的特征在于以下结构：在该化合物中，R 1选自-OR 7，-NR 8 R 9，-NHNR 10 R 11，-NHNHC（X 2）NHR 12，-NHSO 2 NR 8 R 9，-NHNHC（O）R 12， -NHNHSO 2 R 12和-NHC（O）NR 8 R 9。 R7-R12独立地选自氢，烷基，芳基，芳烷基，杂芳基和杂芳烷基。 X1和X2独立于氧和硫组成的组中选择。 R2是氢或卤素。 R3-R6独立地选自氢，卤素，羟基，-NR8R9，硝基，氰基，烷氧基，低级烷基，芳基和芳氧基。

公开(公告)号：US5604207A

公开(公告)日：1997-02-18

申请号：US345072

申请日：1994-11-28

Applicant: Shawn A. DeFrees ,  Federico C. A. Gaeta ,  John J. Gaudino ,  Zhongli Zheng ,  Masaji Hayashi

Inventor： Shawn A. DeFrees ,  Federico C. A. Gaeta ,  John J. Gaudino ,  Zhongli Zheng ,  Masaji Hayashi

IPC: C07H13/06 ,  A61K31/70 ,  A61K31/7024 ,  A61K38/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  C07H3/04 ,  C07H3/06 ,  C07H13/08 ,  C07H13/10 ,  C07H15/04 ,  A61K31/715 ,  A61K31/73

CPC classification number: A61K31/702 ,  A61K31/70 ,  C07H13/08 ,  C07H13/10 ,  C07H15/04 ,  C07H3/04 ,  C07H3/06

Abstract: The inventive compounds are analogues of sialyl Le.sup.x that inhibit cellular adhesion between a selectin and cells that express sialyl Le.sup.x on their surfaces, and their synthetic intermediates. An inventive compound has structure A, ##STR1## wherein Z is hydrogen, C.sub.1 -C.sub.6 acyl or ##STR2## Y is C(O), SO.sub.2, HNC(O), OC(O) or SC(O); R.sup.1 is an aryl, a substituted aryl or a phenyl C.sub.1 -C.sub.3 alkylene group, wherein an aryl group has one five- or six-membered aromatic ring, a fused five/six-membered aromatic ring, or two fused six-membered aromatic rings, which rings are hydrocarbyl, monooxahydrocarbyl, monothiahydrocarbyl, monoazahydrocarbyl or diazahydrocarbyl rings, and a substituted aryl group is an aryl group having a halo, trifluoromethyl, nitro, C.sub.1 -C.sub.18 alkyl, C.sub.1 -C.sub.18 alkoxy, amino, mono-C.sub.1 -C.sub.18 alkylamino, di-C.sub.1 -C.sub.18 alkylamino, benzylamino, C.sub.1 -C.sub.18 alkylbenzylamino, C.sub.1 -C.sub.18 thioalkyl or C.sub.1 -C.sub.18 alkyl carboxamido substituent, or R.sup.1 Y is allyloxycarbonyl or chloroacetyl;R.sup.2 is hydrogen, C.sub.1 -C.sub.18 straight chain, branched chain or cyclic hydrocarbyl, C.sub.1 -C.sub.6 alkyl C.sub.1 -C.sub.5 alkylene .omega.-carboxylate, .omega.-tri(C.sub.1 -C.sub.4 alkyl/phenyl)silyl C.sub.2 -C.sub.4 alkylene, monosaccharide or disaccharide,or OR.sup.2 together form a C.sub.1 -C.sub.18 straight chain, branched chain or cyclic hydrocarbyl carbamate;R.sup.3 is hydrogen or C.sub.1 -C.sub.6 acyl;R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl or benzyl;R.sup.5 is hydrogen, benzyl, methoxybenzyl, dimethoxybenzyl or C.sub.1 -C.sub.6 acyl;R.sup.7 is methyl or hydroxymethyl; andX is C.sub.1 -C.sub.6 acyloxy, C.sub.2 -C.sub.6 hydroxylacyloxy, hydroxy, halo or azido.

Abstract translation: 本发明化合物是唾液酸Lex的类似物，其抑制选择蛋白与表达唾液酸Lex的细胞之间的细胞粘附及其合成中间体。 本发明化合物具有结构A，其中Z是氢，C 1 -C 6酰基或Y是C（O），SO 2，HNC（O），OC（O）或SC（O））。 R 1是芳基，取代的芳基或苯基C 1 -C 3亚烷基，其中芳基具有一个五元或六元芳香环，稠合五元/六元芳环或两个稠合六元芳环 ，其中环是烃基，单恶唑烃基，一硫代烃基，单肼基或二氮杂烃基环，取代的芳基是具有卤素，三氟甲基，硝基，C 1 -C 18烷基，C 1 -C 18烷氧基，氨基，单C 1 -C 18烷基氨基 ，二-C1-C18烷基氨基，苄基氨基，C1-C18烷基苄基氨基，C1-C18硫代烷基或C1-C18烷基甲酰氨基取代基，或R1Y是烯丙氧基羰基或氯乙酰基; R2是氢，C1-C18直链，支链或环状烃基，C1-C6烷基C1-C5亚烷基ω-羧酸酯，ω-三（C1-C4烷基/苯基）甲硅烷基C2-C4亚烷基，单糖或二糖，或 OR2一起形成C1-C18直链，支链或环状烃基氨基甲酸酯; R3是氢或C1-C6酰基; R4是氢，C1-C6烷基或苄基; R5是氢，苄基，甲氧基苄基，二甲氧基苄基或C1-C6酰基; R7是甲基或羟甲基; X为C1-C6酰氧基，C2-C6羟基酰氧基，羟基，卤素或叠氮基。