公开(公告)号：US20190231790A1

公开(公告)日：2019-08-01

申请号：US16377464

申请日：2019-04-08

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： A61K31/5377 ,  C07D407/04 ,  C07D307/93 ,  C07D307/77 ,  A61K31/496 ,  C07D493/04 ,  A61K31/4025 ,  A61K31/397 ,  A61K31/343 ,  A61K31/4525

CPC分类号： A61K31/5377 ,  A61K31/343 ,  A61K31/397 ,  A61K31/4025 ,  A61K31/4525 ,  A61K31/496 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04 ,  C07D493/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

公开(公告)号：US09447112B2

公开(公告)日：2016-09-20

申请号：US14727126

申请日：2015-06-01

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： A01N43/16 ,  C07D493/04 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04

CPC分类号： C07D493/04 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

公开(公告)号：US09045490B2

公开(公告)日：2015-06-02

申请号：US14270121

申请日：2014-05-05

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： A01N43/16 ,  C07D405/00 ,  C07D409/00 ,  C07D493/04

CPC分类号： C07D493/04 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

摘要翻译： 本发明提供式（I）的化合物，其中：X 1，X 2和X 3是杂原子; R4，R5，R6，R7，R8，R9和R10独立地选自H，卤素，-OH，-NO 2，-CN和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 并且Z是任选取代的C 1-8直链或支链脂族，任选地含有1个或更多个双键或三键，其中一个或多个碳任选被R *替代，其中R *是任选取代的环烷基，杂环烷基，芳基或杂芳基; 氨基酸残基，H，-CN，-C（O） - ， - C（O）C（O） - ， - C（O）NR 1 - ， - C（O）NR 11 NR 12 - - （O） - ， - NR 1 CO 2 - ， - O - ， - NR 1 C（O）NR 2 - ， - OC（O）NR 1 - ， - NR 1 NR 2 - - ， - SO 2 - ， - NR 1 - ， - SO 2 NR 1 - ， - NR 1 R 2或-NR 1 SO 2 - ，其中R 1和R 2独立地选自H和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 或其中R *是NR 1 R 2，R 1和R 2任选与氮原子一起形成任选取代的5-12元环，所述环任选地包含1个或多个杂原子或选自-CO - ， - SO - ， - SO 2 - 和-PO-; 或其药学上可接受的盐，酯或前药。

公开(公告)号：US20170224698A1

公开(公告)日：2017-08-10

申请号：US15268854

申请日：2016-09-19

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： A61K31/5377 ,  A61K31/397 ,  A61K31/4025 ,  A61K31/496 ,  A61K31/343 ,  A61K31/4525

CPC分类号： A61K31/5377 ,  A61K31/343 ,  A61K31/397 ,  A61K31/4025 ,  A61K31/4525 ,  A61K31/496 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04 ,  C07D493/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R3, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

公开(公告)号：US08716329B2

公开(公告)日：2014-05-06

申请号：US13925219

申请日：2013-06-24

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： A61K31/35 ,  C07D405/00 ,  C07D411/00

CPC分类号： C07D493/04 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

摘要翻译： 本发明提供式（I）的化合物，其中：X 1，X 2和X 3是杂原子; R4，R5，R6，R7，R8，R9和R10独立地选自H，卤素，-OH，-NO 2，-CN和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 并且Z是任选取代的C 1-8直链或支链脂族，任选地含有1个或更多个双键或三键，其中一个或多个碳任选被R *替代，其中R *是任选取代的环烷基，杂环烷基，芳基或杂芳基; 氨基酸残基，H，-CN，-C（O） - ， - C（O）C（O） - ， - C（O）NR 1 - ， - C（O）NR 11 NR 12 - - （O） - ， - NR 1 CO 2 - ， - O - ， - NR 1 C（O）NR 2 - ， - OC（O）NR 1 - ， - NR 1 NR 2 - - ， - SO 2 - ， - NR 1 - ， - SO 2 NR 1 - ， - NR 1 R 2或-NR 1 SO 2 - ，其中R 1和R 2独立地选自H和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 或其中R *是NR 1 R 2，R 1和R 2任选与氮原子一起形成任选取代的5-12元环，所述环任选地包含1个或多个杂原子或选自-CO - ， - SO - ， - SO 2 - 和-PO-; 或其药学上可接受的盐，酯或前药。

公开(公告)号：US10251890B2

公开(公告)日：2019-04-09

申请号：US15268854

申请日：2016-09-19

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： A61K31/5377 ,  C07D307/77 ,  C07D493/04 ,  C07D307/93 ,  C07D407/04 ,  A61K31/343 ,  A61K31/397 ,  A61K31/4025 ,  A61K31/4525 ,  A61K31/496

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

公开(公告)号：US20150259356A1

公开(公告)日：2015-09-17

申请号：US14727126

申请日：2015-06-01

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： C07D493/04

CPC分类号： C07D493/04 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

摘要翻译： 本发明提供式（I）的化合物，其中：X 1，X 2和X 3是杂原子; R4，R5，R6，R7，R8，R9和R10独立地选自H，卤素，-OH，-NO 2，-CN和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 并且Z是任选取代的C 1-8直链或支链脂族，任选地含有1个或更多个双键或三键，其中一个或多个碳任选被R *替代，其中R *是任选取代的环烷基，杂环烷基，芳基或杂芳基; 氨基酸残基，H，-CN，-C（O） - ， - C（O）C（O） - ， - C（O）NR 1 - ， - C（O）NR 11 NR 12 - - （O） - ， - NR 1 CO 2 - ， - O - ， - NR 1 C（O）NR 2 - ， - OC（O）NR 1 - ， - NR 1 NR 2 - - ， - SO 2 - ， - NR 1 - ， - SO 2 NR 1 - ， - NR 1 R 2或-NR 1 SO 2 - ，其中R 1和R 2独立地选自H和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 或其中R *是NR 1 R 2，R 1和R 2任选与氮原子一起形成任选取代的5-12元环，所述环任选地包含1个或多个杂原子或选自-CO - ， - SO - ， - SO 2 - 和-PO-; 或其药学上可接受的盐，酯或前药。

公开(公告)号：US20150099731A1

公开(公告)日：2015-04-09

申请号：US14270121

申请日：2014-05-05

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： C07D493/04

CPC分类号： C07D493/04 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

公开(公告)号：US08703803B2

公开(公告)日：2014-04-22

申请号：US13624322

申请日：2012-09-21

申请人： University of Kentucky Research Foundation

发明人： Peter A. Crooks ,  Linda P. Dwoskin ,  Roger Papke ,  Guangrong Zheng ,  Sangeetha Sumithran

IPC分类号： A61K31/47 ,  A61K31/44 ,  A61K31/445 ,  A61K31/53 ,  A61K31/40 ,  A61K31/41 ,  A61K31/415 ,  C07D217/00 ,  C07D213/04 ,  C07D401/00 ,  C07D215/10 ,  C07D215/12 ,  A61K31/50 ,  A61K31/497

CPC分类号： C07D213/06 ,  C07D213/02 ,  C07D215/06 ,  C07D217/04 ,  C07D401/04 ,  C07D401/14

摘要： Provided are tris-quaternary ammonium compounds which are modulators of nicotinic acetylocholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse and or gastrointestinal tract disorders.

摘要翻译： 提供了三季铵化合物，其是烟碱型乙酰胆碱受体的调节剂。 还提供了使用化合物调节烟碱乙酰胆碱受体的功能以及用于预防和/或治疗中枢神经系统疾病，物质使用和/或滥用和/或胃肠道疾病的方法。

公开(公告)号：US20130288371A1

公开(公告)日：2013-10-31

申请号：US13925219

申请日：2013-06-24

申请人： University of Kentucky

发明人： Peter A. Crooks ,  Craig T. Jordan ,  Xiaochen Wei

IPC分类号： C07D307/93 ,  C07D407/04

CPC分类号： C07D493/04 ,  C07D307/77 ,  C07D307/93 ,  C07D407/04

摘要： The present invention provides compounds of the formula (I) wherein: X1, X2 and X3 are heteroatoms; R4, R5, R6, R7, R8, R9 and R10 are independently selected from H, halo, —OH, —NO2, —CN and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and Z is optionally substituted C1-8 straight-chained or branched aliphatic, optionally containing 1 or more double or triple bonds, wherein one or more carbons are optionally replaced by R* wherein R* is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; an amino acid residue, H, —CN, —C(O)—, —C(O)C(O)—, —C(O)NR1—, —C(O)NR1NR2—, —C(O)O—, —OC(O)—, —NR1CO2—, —O—, —NR1C(O)NR2—, —OC(O)NR1—, —NR1NR2—, —NR1C(O)—, —S—, —SO—, —SO2—, —NR1—, —SO2NR1—, —NR1R2, or —NR1SO2—, wherein R1 and R2 are independently selected from H and optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or where R* is NR1R2, R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, said ring optionally comprising 1 or more heteroatoms or a group selected from —CO—, —SO—, —SO2— and —PO—; or a pharmaceutically acceptable salt, ester or prodrug thereof.

摘要翻译： 本发明提供式（I）的化合物，其中：X 1，X 2和X 3是杂原子; R4，R5，R6，R7，R8，R9和R10独立地选自H，卤素，-OH，-NO 2，-CN和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 并且Z是任选取代的C 1-8直链或支链脂族，任选地含有1个或更多个双键或三键，其中一个或多个碳任选被R *替代，其中R *是任选取代的环烷基，杂环烷基，芳基或杂芳基; 氨基酸残基，H，-CN，-C（O） - ， - C（O）C（O） - ， - C（O）NR 1 - ， - C（O）NR 11 NR 12 - - （O） - ， - NR 1 CO 2 - ， - O - ， - NR 1 C（O）NR 2 - ， - OC（O）NR 1 - ， - NR 1 NR 2 - - ， - SO 2 - ， - NR 1 - ， - SO 2 NR 1 - ， - NR 1 R 2或-NR 1 SO 2 - ，其中R 1和R 2独立地选自H和任选取代的脂族，环烷基，杂环烷基，芳基或杂芳基; 或其中R *是NR 1 R 2，R 1和R 2任选与氮原子一起形成任选取代的5-12元环，所述环任选地包含1个或多个杂原子或选自-CO - ， - SO - ， - SO 2 - 和-PO-; 或其药学上可接受的盐，酯或前药。