公开(公告)号：US07041696B2

公开(公告)日：2006-05-09

申请号：US10457181

申请日：2003-06-09

申请人： John August Wos ,  David Lindsey Soper ,  Steven Victor O'Neil ,  Yili Wang ,  Kofi Abeka Oppong ,  Michael Christopher Laufersweiler ,  Jian Chen ,  Biswanath De ,  Thomas Prosser Demuth, Jr.

发明人： John August Wos ,  David Lindsey Soper ,  Steven Victor O'Neil ,  Yili Wang ,  Kofi Abeka Oppong ,  Michael Christopher Laufersweiler ,  Jian Chen ,  Biswanath De ,  Thomas Prosser Demuth, Jr.

IPC分类号： C07D487/04 ,  A61K31/403 ,  A61P29/00

CPC分类号： C07D471/04 ,  C07D487/04

摘要： The present invention relates to interleukin-1β converting enzyme inhibitors having the formula: R is a carbocyclic or heterocyclic ring; R1 is a cysteine trap; R2a, R2a′, R2b, and R2b′ are each independently hydrogen, C1–C4 alkyl, C1–C4 alkoxy, and mixtures thereof; or R2a′ and R2b′ can taken together to form a double bond; L and L1 are linking groups having the formula: T is selected from the group consisting of: i) —NR6—; ii) —O—; iii) —NR6S(O)2—; iv) —S(O)2NR6—; and v) mixtures thereof; R6 is hydrogen, substituted or unsubstituted C1–C20 linear, branched, or cyclic alkyl, C6–C20 aryl, C7–C20 alkylenearyl, and mixtures thereof; the indices w, w1, and w2 are each independently 0 or 1; i) hydrogen; ii) C1–C4 linear, branched, and cyclic alkyl; iii) R3a and R3b or R4a, and R4b can be taken together to form a carbonyl unit; iv) two R3a or two R3b units from adjacent carbon atoms or two R4a or two R4b units from adjacent carbon atoms can be taken together to form a double bond; and v) mixtures thereof; the index m is from 0 to 5; the index n is from 0 to 5.

摘要翻译： 本发明涉及具有下式的白细胞介素-1β转换酶抑制剂：R是碳环或杂环; R 1是半胱氨酸阱; R 2a，R 2a，R 2b和R 2b'各自独立地为氢，C

公开(公告)号：US07001899B2

公开(公告)日：2006-02-21

申请号：US10457720

申请日：2003-06-09

申请人： John August Wos ,  Yili Wang ,  Kofi Abeka Oppong ,  Steven Victor O'Neil ,  Michael Christopher Laufersweiler ,  David Lindsey Soper ,  Biswanath De ,  Thomas Prosser Demuth, Jr.

发明人： John August Wos ,  Yili Wang ,  Kofi Abeka Oppong ,  Steven Victor O'Neil ,  Michael Christopher Laufersweiler ,  David Lindsey Soper ,  Biswanath De ,  Thomas Prosser Demuth, Jr.

IPC分类号： C07D405/12 ,  C07D405/14 ,  C07D417/12 ,  C07D417/14 ,  A61K31/554

CPC分类号： C07D405/12 ,  A61K38/00 ,  C07D405/14 ,  C07D409/14 ,  C07D417/12 ,  C07D417/14 ,  C07K5/0202 ,  C07K5/06078

摘要： The present invention relates to novel compounds, compositions comprising said compounds, and uses thereof, said compounds having the formula: wherein each X is independently selected from: i) —C(W)2—; ii) —C(O)—; iii) —NR2—; iv) —S—; v) —S(O)—; vi) —S(O)2—; vii) two units, one from each adjacent X unit, can be taken together to form a substituted or unsubstituted double bond having the formula —CW═CW—; wherein each W is hydrogen of a unit having the formula —(L2)j—R2, the index j is 0 or 1; R is a carbocyclic or heterocyclic aryl ring; R1 is a cysteine trap; each R2 is independently a suitable substituent; and L, L1, and L2 are linking units.

摘要翻译： 本发明涉及新化合物，包含所述化合物的组合物及其用途，所述化合物具有下式：化学式id =“CHEM-US-00001”num =“000

公开(公告)号：US07138395B2

公开(公告)日：2006-11-21

申请号：US10457188

申请日：2003-06-09

申请人： Steven Victor O'Neil ,  Michael Christopher Laufersweiler ,  Yili Wang ,  Kofi Abeka Oppong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De ,  Thomas Prosser Demuth, Jr.

发明人： Steven Victor O'Neil ,  Michael Christopher Laufersweiler ,  Yili Wang ,  Kofi Abeka Oppong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De ,  Thomas Prosser Demuth, Jr.

IPC分类号： C07D471/04 ,  C07D498/04 ,  A61K31/4995 ,  A61K31/537 ,  A61P29/00

CPC分类号： C07D471/04 ,  C07D487/04

摘要： The present invention relates to novel compounds, compositions comprising said compounds, and uses thereof, said compounds having the formula: X is —CH2—, —O— or —NR9—; R is a carbocyclic or heterocyclic ring; R1 is a cysteine trap; R2a, R2a′, R2b, and R2b′ are each independently hydrogen, C1–C4 alkyl, C1–C4 alkoxy, and mixtures thereof; or R2a′ and R2b′ can taken together to form a double bond; R9 is hydrogen or a unit having the formula -L2-R10; L is the same as defined herein above; R10 is hydrogen; substituted or unsubstituted C1–C6 linear; branched, or cyclic hydrocarbyl; substituted or unsubstituted aryl; substituted or unsubstituted C1–C9 heterocyclic; and substituted or unsubstituted heteroaryl.

摘要翻译： 本发明涉及新化合物，包含所述化合物的组合物及其用途，所述具有下式的化合物：X为-CH 2 - ， - O-或-NR 9 > - ; R是碳环或杂环; R 1是半胱氨酸阱; R 2a，R 2a，R 2b和R 2b'各自独立地为氢，C

公开(公告)号：USRE43372E1

公开(公告)日：2012-05-08

申请号：US12479532

申请日：2009-06-05

申请人： Mitchell Anthony deLong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De

发明人： Mitchell Anthony deLong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De

IPC分类号： C07C405/00 ,  A61K31/5575

CPC分类号： C07C405/0041 ,  C07C405/00 ,  C07C405/0016

摘要： Compounds having the general structure: which are useful for the treatment of a variety of diseases and conditions, such as bone disorders.

摘要翻译： 具有一般结构的化合物：其可用于治疗各种疾病和病症，例如骨骼疾病。

公开(公告)号：US06451859B1

公开(公告)日：2002-09-17

申请号：US09914531

申请日：2001-08-29

申请人： Mitchell Anthony deLong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De

发明人： Mitchell Anthony deLong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De

IPC分类号： C07C40500

CPC分类号： C07D333/36 ,  C07C59/215 ,  C07C59/56 ,  C07C59/72 ,  C07C235/26 ,  C07C251/06 ,  C07C259/06 ,  C07C311/51 ,  C07C327/22 ,  C07C405/00 ,  C07C2601/08 ,  C07D277/64 ,  C07D307/46 ,  C07D307/66 ,  C07D307/80 ,  C07D333/56

摘要： Compounds having a structure according to the following formula: are effective in treating disorders such as bone disorders and glaucoma in a subject in need thereof.

摘要翻译： 具有根据下式的结构的化合物在有需要的受试者中有效治疗诸如骨病和青光眼的疾病。

公开(公告)号：US06410780B1

公开(公告)日：2002-06-25

申请号：US09647381

申请日：2000-09-28

申请人： Mitchell Anthony deLong ,  Jack Snyder Amburgey, Jr. ,  John August Wos ,  Biswanath De ,  David Lindsey Soper

发明人： Mitchell Anthony deLong ,  Jack Snyder Amburgey, Jr. ,  John August Wos ,  Biswanath De ,  David Lindsey Soper

IPC分类号： C07C6974

CPC分类号： C07D307/42 ,  C07C239/18 ,  C07C251/44 ,  C07C405/00 ,  C07C2601/08 ,  C07D257/04 ,  C07D333/16

摘要： The invention provides novel prostaglandin analogs. In particular, the present invention relates to compounds having a structure according to formula (I) wherein R1, R2, R3, R4, R5, R6, W, X, Z, a, b, p and q are defined below. This invention also includes optical isomers, diastereomers and enantiomers of formula (I), and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof. The compounds of the present invention are useful for the treatment of a variety of diseases and conditions, such as bone disorders and glaucoma. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment for bone disorders and glaucoma using these compounds or the compositions containing them.

摘要翻译： 本发明提供了新的前列腺素类似物。 特别地，本发明涉及具有式（I）结构的化合物，其中R1，R2，R3，R4，R5，R6，W，X，Z，a，b，p和q定义如下。 本发明还包括式（I）的光学异构体，非对映异构体和对映体及其药学上可接受的盐，可生物水解的酰胺，酯和酰亚胺。 本发明的化合物可用于治疗各种疾病和病症，例如骨骼疾病和青光眼。 因此，本发明还提供包含这些化合物的药物组合物。 本发明还提供了使用这些化合物或含有它们的组合物治疗骨病和青光眼的方法。

公开(公告)号：US6048895A

公开(公告)日：2000-04-11

申请号：US148538

申请日：1998-09-04

申请人： John August Wos ,  Mitchell Anthony deLong ,  Jack S. Amburgey, Jr. ,  Haiyan George Dai ,  Biswanath De ,  David Lindsey Soper

发明人： John August Wos ,  Mitchell Anthony deLong ,  Jack S. Amburgey, Jr. ,  Haiyan George Dai ,  Biswanath De ,  David Lindsey Soper

IPC分类号： A61K31/5575 ,  A61K31/557 ,  A61P19/08 ,  A61P19/10 ,  A61P27/06 ,  A61P43/00 ,  C07C59/11 ,  C07C69/675 ,  C07C229/28 ,  C07C259/06 ,  C07C317/06 ,  C07C321/16 ,  C07C405/00 ,  A61K31/215 ,  C07C69/76

CPC分类号： C07C405/0041 ,  A61K31/557 ,  C07C405/00

摘要： The invention provides novel PGF analogs. In particular, the present invention relates to compounds having a structure according to the following formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X, and Z are as defined. This invention also includes optical isomers, diastereomers and enantiomers of the formula above, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof.The compounds of the present invention are useful for the treatment of a variety of diseases and conditions, such as bone disorders and glaucoma. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment for bone disorders and glaucoma using theses compounds or the compositions containing them.

摘要翻译： 本发明提供新颖的PGF类似物。 特别地，本发明涉及具有下式结构的化合物：其中R1，R2，R3，R4，X和Z如上所定义。 本发明还包括上式的光学异构体，非对映异构体和对映异构体及其药学上可接受的盐，可生物水解的酰胺，酯和酰亚胺。 本发明的化合物可用于治疗各种疾病和病症，例如骨骼疾病和青光眼。 因此，本发明还提供包含这些化合物的药物组合物。 本发明还提供了使用这些化合物或含有它们的组合物治疗骨疾病和青光眼的方法。

公开(公告)号：US06586463B2

公开(公告)日：2003-07-01

申请号：US09946021

申请日：2001-09-04

申请人： Mitchell Anthony deLong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De

发明人： Mitchell Anthony deLong ,  David Lindsey Soper ,  John August Wos ,  Biswanath De

IPC分类号： C07C40500

CPC分类号： C07C405/0041 ,  C07C405/00 ,  C07C405/0016

摘要： Compounds having the general structure: which are useful for the treatment of a variety of diseases and conditions, such as bone disorders.

摘要翻译： 具有一般结构的化合物：其可用于治疗各种疾病和病症，例如骨骼疾病。

公开(公告)号：US06444840B1

公开(公告)日：2002-09-03

申请号：US09647380

申请日：2000-09-28

申请人： Mitchell Anthony deLong ,  Jack Snyder Amburgey, Jr. ,  John August Wos ,  Biswanath De ,  David Lindsey Soper

发明人： Mitchell Anthony deLong ,  Jack Snyder Amburgey, Jr. ,  John August Wos ,  Biswanath De ,  David Lindsey Soper

IPC分类号： C07C6974

CPC分类号： C07D257/04 ,  C07C239/12 ,  C07C251/44 ,  C07C405/0041 ,  C07D307/64 ,  C07D333/18

摘要： The invention provides novel prostaglandin analogs. In particular, the present invention relates to compounds having a structure according to formula (I) wherein R1, R2, R3, R4, R5, R6, W, X, Z, a, b, p and q are defined below. This invention also includes optical isomers, diastereomers and enantiomers of formula (I), and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof. The compounds of the present invention are useful for the treatment of a variety of diseases and conditions, such as bone disorders and glaucoma. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment for bone disorders and glaucoma using these compounds or the compositions containing them.

摘要翻译： 本发明提供了新的前列腺素类似物。 特别地，本发明涉及具有式（I）结构的化合物，其中R1，R2，R3，R4，R5，R6，W，X，Z，a，b，p和q定义如下。 本发明还包括式（I）的光学异构体，非对映异构体和对映体及其药学上可接受的盐，可生物水解的酰胺，酯和酰亚胺。 本发明的化合物可用于治疗各种疾病和病症，例如骨骼疾病和青光眼。 因此，本发明还提供包含这些化合物的药物组合物。 本发明还提供了使用这些化合物或含有它们的组合物治疗骨病和青光眼的方法。

公开(公告)号：US6066751A

公开(公告)日：2000-05-23

申请号：US148539

申请日：1998-09-04

申请人： John August Wos ,  Jack Snyder Amburgey, Jr. ,  Mitchell Anthony deLong ,  Yili Wang ,  Haiyan George Dai ,  Biswanath De

发明人： John August Wos ,  Jack Snyder Amburgey, Jr. ,  Mitchell Anthony deLong ,  Yili Wang ,  Haiyan George Dai ,  Biswanath De

IPC分类号： C07D301/14 ,  C07C405/00 ,  C07D303/12

CPC分类号： C07C405/00

摘要： It has been surprisingly discovered that the disadvantages of the lengthy literature procedures to synthesize 13,14-dihydro prostaglandin A, E, and F derivatives can be overcome using a novel Methyl 7-(2-hydroxy-5-(2-(2-oxiranyl)ethyl)-4-(1,1,2,2 tetramethyl-1-silapropoxy)cyclopentyl) heptanoate intermediate, which can be synthesized from commercially available Methyl 7-[3-(R)-hydroxy-5-oxo-1-cyclopent-1-yl] heptanoate. This novel intermediate can be coupled with oxygen, carbon, sulfur, and nitrogen nucleophiles, in the presence of a base or a Lewis acid, in a ring-opening process to provide 13,14-dihydro prostaglandin A, E, and F derivatives.

摘要翻译： 已经令人惊讶地发现，使用新的7-（2-羟基-5-（2-（2-（2-甲氧基乙氧基）苯基）甲基丙烯酸甲酯，可以克服长时间合成13,14-二氢前列腺素A，E和F衍生物的文献程序的缺点， 环氧乙烷基）乙基）-4-（1,1,2,2-四甲基-1-硅基丙氧基）环戊基）庚酸酯中间体，其可以从市售的7- [3-（R） - 羟基-5-氧代-1 环戊-1-基]庚酸乙酯。 这种新型中间体可以在碱或路易斯酸的存在下与氧，碳，硫和氮亲核试剂在开环过程中偶联，得到13,14-二氢前列腺素A，E和F衍生物。