公开(公告)号：US6093697A

公开(公告)日：2000-07-25

申请号：US902338

申请日：1997-07-29

申请人： Joseph Larner ,  John Price ,  Thomas Piccariello ,  Laura Huang

发明人： Joseph Larner ,  John Price ,  Thomas Piccariello ,  Laura Huang

IPC分类号： C07H15/04 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61P3/08 ,  A61P3/10 ,  C07H15/207 ,  C07H17/04 ,  C07H15/00

CPC分类号： C07H17/04 ,  C07H15/207 ,  Y10S514/866

摘要： Compounds are disclosed which have the formula (I) ##STR1## wherein R.sub.1 -R.sub.2 are each independently selected from the group consisting of: (a) a hydrogen atom; and (b) a lower alkyl group, straight or branched chain, having 1 to 8 carbon atoms; or R.sub.1 -R.sub.2 and the nitrogen atom to which they are bonded may together form a heterocyclic group; R.sub.3 -R.sub.10 are each independently selected from the group consisting of: (a) a hydrogen atom; (b) an alkyl group, straight or branched chain, having 1 to 24 carbon atoms; (c) a cycloalkyl group having 3 to 10 carbon atoms; (d) an alkenyl group, straight or branched chain, having 2 to 24 carbon atoms; (e) a cycloalkenyl group having 4 to 10 carbon atoms and one or more non-adjacent double bonds; (f) an aryl group having 6 to 10 carbon atoms; (g) an aralkyl group having 7 to 34 carbons atoms; (h) a heteroaryl group having 4 to 9 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; (i) a carboxyalkyl group, straight or branched chain, having 2 to 24 carbon atoms; (j) a carboxyaryl group having 7 to 34 carbon atoms; and (k) a heterocyclic group having 2 to 9 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, sulfur and nitrogen; or any adjacent two of R.sub.3 -R.sub.10 may together form a cycloalkyl group or heterocyclic group; and X.sub.1 and X.sub.2 are each independently selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom. Pharmaceutical compositions containing these compounds and the use thereof for the treatment of disorders of glucose metabolism are also disclosed.

摘要翻译： 公开了具有式（I）的化合物，其中R 1 -R 2各自独立地选自：（a）氢原子; 和（b）具有1至8个碳原子的直链或支链的低级烷基; 或R 1 -R 2和它们所键合的氮原子可以一起形成杂环基; R3-R10各自独立地选自：（a）氢原子; （b）具有1至24个碳原子的直链或支链烷基; （c）碳原子数3〜10的环烷基; （d）具有2至24个碳原子的直链或支链烯基; （e）具有4-10个碳原子和一个或多个不相邻双键的环烯基; （f）具有6〜10个碳原子的芳基; （g）碳原子数为7〜34的芳烷基; （h）具有4至9个碳原子的杂芳基和至少一个选自氧，氮和硫的杂原子; （i）具有2至24个碳原子的直链或支链的羧基烷基; （j）具有7至34个碳原子的羧基芳基; 和（k）具有2至9个碳原子的杂环基和至少一个选自氧，硫和氮的杂原子; 或R 3 -R 10任意相邻的两个可以一起形成环烷基或杂环基; X 1和X 2各自独立地选自氧原子，硫原子和氮原子。 还公开了含有这些化合物的药物组合物及其用于治疗葡萄糖代谢紊乱的用途。

公开(公告)号：US10150792B2

公开(公告)日：2018-12-11

申请号：US12941599

申请日：2010-11-08

申请人： John D. Price ,  Thomas Piccariello ,  Robert A. Oberlender ,  Michaela E. Mulhare ,  Scott B. Palmer

发明人： John D. Price ,  Thomas Piccariello ,  Robert A. Oberlender ,  Michaela E. Mulhare ,  Scott B. Palmer

IPC分类号： C07H23/00 ,  C07F9/00 ,  C08B37/08 ,  C08B37/00 ,  C07C229/76

摘要： Bismuth-containing compounds include bismuth and a biologically active agent coordinated to the bismuth. The biologically active agent includes at least one heteroatom configured for coordination with the bismuth. Coordination polymers include a polymer matrix that contains a bismuth-containing compound. Methods for modulating a pharmacokinetic property of a biologically active agent include coordinating the biologically active agent to bismuth to form a bismuth-containing compound, and administering the bismuth-containing compound orally to a patient. Methods for treating Parkinson's disease, methods for treating hypothyroidism, methods for treating ulcerative colitis, and methods for treating cancer each include administering a bismuth-containing compound to a patient.

公开(公告)号：US07718619B2

公开(公告)日：2010-05-18

申请号：US12202096

申请日：2008-08-29

申请人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

发明人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

IPC分类号： A61K38/00 ,  A61K51/00 ,  A61K31/785 ,  G01N33/53 ,  G01N33/00

CPC分类号： A61K31/165 ,  A61K47/542 ,  C07C237/06 ,  Y02A50/415 ,  Y10S436/901 ,  Y10T436/173845

摘要： The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

公开(公告)号：US07678771B2

公开(公告)日：2010-03-16

申请号：US12202146

申请日：2008-08-29

申请人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

发明人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

IPC分类号： A61K38/00 ,  A61K51/00 ,  A61K31/785 ,  G01N33/53 ,  G01N33/00

CPC分类号： A61K31/165 ,  A61K47/542 ,  C07C237/06 ,  Y10S436/901 ,  Y10T436/173845

摘要： The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

公开(公告)号：US07678770B2

公开(公告)日：2010-03-16

申请号：US12201739

申请日：2008-08-29

申请人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

发明人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

IPC分类号： A61K38/00 ,  A61K51/00 ,  A61K31/785 ,  G01N33/53 ,  G01N33/00

CPC分类号： A61K31/165 ,  A61K47/542 ,  C07C237/06 ,  Y02A50/415 ,  Y10S436/901 ,  Y10T436/173845

摘要： The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

公开(公告)号：US07659253B2

公开(公告)日：2010-02-09

申请号：US12131923

申请日：2008-06-02

申请人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

发明人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

IPC分类号： A61K38/00 ,  A61K51/00 ,  A61K31/785 ,  G01N33/53 ,  G01N33/00

CPC分类号： A61K31/27 ,  A61K31/165 ,  A61K47/542 ,  C07C237/06 ,  Y10S436/901 ,  Y10T436/173845

摘要： The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

公开(公告)号：US20090186828A1

公开(公告)日：2009-07-23

申请号：US12239087

申请日：2008-09-26

申请人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

发明人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

IPC分类号： A61K38/06 ,  A61K31/165 ,  A61K38/05

CPC分类号： A61K31/165 ,  A61K47/542 ,  C07C237/06 ,  Y02A50/415 ,  Y10S436/901 ,  Y10T436/173845

摘要： The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

公开(公告)号：US20090143338A1

公开(公告)日：2009-06-04

申请号：US12317931

申请日：2008-12-30

申请人： Thomas Piccariello

发明人： Thomas Piccariello

IPC分类号： A61K31/663 ,  A61K31/555

CPC分类号： C07F3/02 ,  A61K47/52 ,  A61K47/547 ,  A61K47/55 ,  A61K47/552 ,  C07F3/003 ,  C07F3/06 ,  C07H21/02

摘要： A metal coordination complex of a biologically active moiety and a metal is disclosed. The complex confers to the biologically active moiety an improved performance which can include potency, stability, absorbability, targeted delivery, and combinations thereof.

摘要翻译： 公开了生物活性部分和金属的金属配位络合物。 复合物赋予生物活性部分改进的性能，其可以包括效力，稳定性，吸收性，靶向递送及其组合。

公开(公告)号：US20090137489A1

公开(公告)日：2009-05-28

申请号：US12203132

申请日：2008-09-02

申请人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

发明人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

IPC分类号： A61K38/08 ,  C07C229/02 ,  C07K5/06 ,  C07K5/08 ,  C07K5/10 ,  C07K7/06 ,  A61P25/00 ,  A61K31/198 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07

CPC分类号： A61K31/165 ,  A61K47/542 ,  C07C237/06 ,  Y10S436/901 ,  Y10T436/173845

摘要： The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

公开(公告)号：US20090137487A1

公开(公告)日：2009-05-28

申请号：US12202941

申请日：2008-09-02

申请人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

发明人： Travis Mickle ,  Suma Krishnan ,  Barney Bishop ,  Christopher Lauderback ,  James Scott Moncrief ,  Robert Oberlender ,  Thomas Piccariello ,  Bernhard J. Paul ,  Christopher A. Verbicky

IPC分类号： A61K38/08 ,  A61K38/05 ,  A61K38/06 ,  A61P25/28 ,  A61K31/198 ,  A61K38/07

CPC分类号： A61K31/165 ,  A61K47/542 ,  C07C237/06 ,  Y10S436/901 ,  Y10T436/173845

摘要： The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

摘要翻译： 本发明描述了使用包含与苯丙胺共价连接的化学部分的化合物，组合物和方法。 这些化合物和组合物可用于减少或预防滥用和过量安非他明。 这些化合物和组合物特别用于提供某些障碍（例如注意力缺陷多动障碍（ADHD），ADD，发作性睡病和肥胖）的耐药性替代治疗。 苯丙胺的口服生物利用度维持在治疗有用的剂量。 在较高剂量下，生物利用度显着降低，从而提供减少口服滥用责任的方法。 此外，本发明的化合物和组合物通过肠胃外途径（例如静脉内或鼻内给药）降低苯丙胺的生物利用度，进一步限制其滥用责任。