公开(公告)号：WO2003035005A3

公开(公告)日：2003-05-01

申请号：PCT/US2002/034395

申请日：2002-10-28

Applicant: UNIVERSITY OF CONNECTICUT ,  MAKRIYANNIS, Alexandros ,  LIU, Qian

Inventor： MAKRIYANNIS, Alexandros ,  LIU, Qian

IPC: C07D413/06

Abstract: One aspect of the invention is concerned with cannabimimetic heteroindane analogs having affinities and/or selectivities for a cannabinoid receptor. A further aspect of the invention is concerned with pharmaceutical preparations employing the inventive analogs and methods of administering therapeutically effective amounts of the inventive analogs to provide a physiological effect.

公开(公告)号：WO2003035005A2

公开(公告)日：2003-05-01

申请号：PCT/US2002/034395

申请日：2002-10-28

Applicant: UNIVERSITY OF CONNECTICUT ,  MAKRIYANNIS, Alexandros ,  LIU, Qian

Inventor： MAKRIYANNIS, Alexandros ,  LIU, Qian

IPC: A61K

CPC classification number: C07D231/56 ,  C07D401/06

Abstract: One aspect of the invention is concerned with cannabimimetic heteroindane analogs having affinities and/or selectivities for a cannabinoid receptor. A further aspect of the invention is concerned with pharmaceutical preparations employing the inventive analogs and methods of administering therapeutically effective amounts of the inventive analogs to provide a physiological effect.

Abstract translation: 本发明的一个方面涉及对大麻素受体具有亲和力和/或选择性的大麻拟嘌呤类似物。 本发明的另一方面涉及使用本发明类似物的药物制剂和给予治疗有效量的本发明类似物以提供生理效应的方法。

公开(公告)号：WO2003020217A3

公开(公告)日：2003-03-13

申请号：PCT/US2002/027644

申请日：2002-08-29

Applicant: UNIVERSITY OF CONNECTICUT ,  MAKRIYANNIS, Alexandros ,  LIU, Qian

Inventor： MAKRIYANNIS, Alexandros ,  LIU, Qian

IPC: C07D401/12

Abstract: One aspect of the invention is concerned with cannabimimetic pyrazole analogs. Another aspect of the invention is concerned with new and improved pyrazole analogs having high affinities and/or selectivities for the GB 1 cannabinoid receptor. A further aspect of the invention is concerned with pharmaceutical preparations employing the inventive analogs and methods of administering therapeutically effective amounts of the inventive analogs to provide a physiological effect.

公开(公告)号：WO1997045407A1

公开(公告)日：1997-12-04

申请号：PCT/US1997009613

申请日：1997-05-30

Applicant: UNIVERSITY OF CONNECTICUT

Inventor： UNIVERSITY OF CONNECTICUT ,  MAKRIYANNIS, Alexandros ,  LIN, Sonyan ,  HILL, William, Adam

IPC: C07D207/46

CPC classification number: A61K31/4015 ,  A61K31/185 ,  A61K31/255 ,  C07D207/46

Abstract: Disclosed is a method of inhibiting anandamide amidase in an individual or animal and novel inhibitors of anandamide amidase. The disclosed method and novel compounds can be used to reduce pain in an individual or animal suffering from pain, reducing nausea in an individual undergoing chemotherapy, for example cancer chemotherapy, suppressing appetite in an individual, reducing intraocular pressure in the eye of an individual or animal suffering from glaucoma and suppressing the immune system in an individual with an organ transplant.

Abstract translation: 公开了一种抑制个体或动物中的酰胺酰胺酶的方法和新颖的氨基酰胺酰胺酶抑制剂。 所公开的方法和新化合物可用于减轻患有疼痛的个体或动物的疼痛，减少经历化疗的个体的恶心，例如癌症化学疗法，抑制个体的食欲，降低个体眼中的眼内压或 患有青光眼的动物和用器官移植抑制个体的免疫系统。

公开(公告)号：WO2010104488A1

公开(公告)日：2010-09-16

申请号：PCT/US2009/001054

申请日：2009-02-19

Applicant: UNIVERSITY OF CONNECTICUT ,  MAKRIYANNIS, Alexandros ,  VEMURI, Venkata, Kiran ,  THOTAPALLY, Rajesh ,  OLSZEWSKA, Teresa

Inventor： MAKRIYANNIS, Alexandros ,  VEMURI, Venkata, Kiran ,  THOTAPALLY, Rajesh ,  OLSZEWSKA, Teresa

IPC: A01N43/50 ,  A61K31/415

CPC classification number: C07D231/14 ,  C07D233/90 ,  C07D401/10 ,  C07D405/12 ,  C07D409/04

Abstract: Disclosed are biologically active hetero pyrrole analogs such as imidazoles, thiazoles, oxazoles and pyrazoles capable of interacting with the CB1 and/or CB2 cannabinoid receptors. Aspects disclose hetero pyrrole analogs acting as CB1 and/or CB 1 receptor antagonists, having selectivity for the CB 1 or CB2 receptor, acting as neutral antagonists, acting preferentially on CB 1 receptors located in the peripheral nervous system, and/or acting as nitric oxide donors. Pharmaceutical preparations employing the disclosed analogs and methods of administering therapeutically effective amounts of the disclosed analogs to provide a physiological effect are also disclosed.

Abstract translation: 公开了能够与CB1和/或CB2大麻素受体相互作用的生物活性杂吡咯类似物，例如咪唑，噻唑，恶唑和吡唑。 方面公开了作为CB1和/或CB1受体拮抗剂的杂吡咯类似物，其具有CB 1或CB 2受体的选择性，作为中性拮抗剂，优先作用于位于周围神经系统中的CB 1受体和/或作为硝酸 氧化物供体。 还公开了使用公开的类似物的药物制剂和施用治疗有效量的所公开的类似物以提供生理作用的方法。

公开(公告)号：WO2008013963A2

公开(公告)日：2008-01-31

申请号：PCT/US2007/016953

申请日：2007-07-27

Applicant: UNIVERSITY OF CONNECTICUT ,  MAKRIYANNIS, Alexandros ,  NIKAS, Spyridon, P. ,  ALAPAFUJA, Shakiru, O. ,  SHUKLA, Vidyanand, G.

Inventor： MAKRIYANNIS, Alexandros ,  NIKAS, Spyridon, P. ,  ALAPAFUJA, Shakiru, O. ,  SHUKLA, Vidyanand, G.

IPC: A61K31/4745

CPC classification number: C07D213/75 ,  C07C17/16 ,  C07C45/41 ,  C07C45/44 ,  C07C45/45 ,  C07C45/673 ,  C07C49/233 ,  C07C49/255 ,  C07C49/84 ,  C07C69/712 ,  C07C69/738 ,  C07C271/12 ,  C07C271/14 ,  C07C271/16 ,  C07C271/24 ,  C07C271/38 ,  C07C271/58 ,  C07C309/68 ,  C07C309/81 ,  C07C309/82 ,  C07C2601/14 ,  C07C2603/74 ,  C07D213/30 ,  C07D213/40 ,  C07D213/50 ,  C07D263/56 ,  C07D271/10 ,  C07D275/06 ,  C07D277/64 ,  C07C22/04 ,  C07C47/277 ,  C07C47/575 ,  C07C49/83

Abstract: Disclosed are compounds of formula R-X-Y that may be used to inhibit the action of fatty acid amide hydrolase (FAAH). Inhibition of fatty acid amide hydrolase (FAAH) will slow the normal degradation and inactivation of endogenous cannabinoid ligands by FAAH hydrolysis and allow higher levels of those endogenous cannabinergic ligands to remain present. These higher levels of endocannabinoid ligands provide increased stimulation of the cannabinoid CBl and CB2 receptors and produce physiological effects related to the activation of the cannabinoid receptors. They will also enhance the effects of other exogenous cannabinergic ligands and allow them to produce their effects at lower concentrations as compared to systems in which fatty acid amide hydrolase (FAAH) action is hot inhibited. Thus, a compound that inhibits the inactivation of endogenous cannabinoid ligands by fatty acid amide hydrolase (FAAH) may increase the levels of endocannabinoids and, thus, enhance the activation of cannabinoid receptors. Thus, the compound may not directly modulate the cannabinoid receptors but has the effect of indirectly stimulating the cannabinoid receptors by increasing the levels of endocannabinoid ligands. It may also enhance the effects and duration of action of other exogenous cannabinergic ligands that are administered in order to elicit a cannabinergic response.

Abstract translation: 公开了可用于抑制脂肪酸酰胺水解酶（FAAH）作用的式R-X-Y的化合物。 脂肪酸酰胺水解酶（FAAH）的抑制将通过FAAH水解减缓内源性大麻素配体的正常降解和失活，并允许更高水平的那些内源性大麻素能配体保持存在。 这些更高水平的内源性大麻素配体提供对大麻素CB1和CB2受体的增加的刺激，并产生与大麻素受体活化相关的生理作用。 与其中脂肪酰胺水解酶（FAAH）作用被热抑制的系统相比，它们还将增强其他外源性大麻素配体的作用，并使它们以较低的浓度产生它们的作用。 因此，通过脂肪酰胺水解酶（FAAH）抑制内源性大麻素配体失活的化合物可能增加内源性大麻素的含量，从而增强大麻素受体的活化。 因此，化合物不能直接调节大麻素受体，而是通过增加内源性大麻素配体的水平来间接刺激大麻素受体的作用。 它还可以增强其它外源性大麻素能配体的作用和持续时间，以引发大麻素应答。

公开(公告)号：WO2006044381A2

公开(公告)日：2006-04-27

申请号：PCT/US2005/036524

申请日：2005-10-12

Applicant: UNIVERSITY OF CONNECTICUT ,  MAKRIYANNIS, Alexandros ,  LI, Chen ,  LU, Dai

Inventor： MAKRIYANNIS, Alexandros ,  LI, Chen ,  LU, Dai

IPC: A61K31/16 ,  C07C235/06

CPC classification number: C07C233/21 ,  C07C233/09 ,  C07C233/11 ,  C07C233/29 ,  C07C233/36 ,  C07C235/08 ,  C07C235/28 ,  C07C235/50 ,  C07C237/16 ,  C07C247/08 ,  C07C255/23 ,  C07C271/12 ,  C07C271/16 ,  C07C271/24 ,  C07C271/28 ,  C07C331/22 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/14 ,  C07C2602/42 ,  C07C2603/74 ,  C07D277/18 ,  C07D277/46

Abstract: One aspect of this disclosure relates generally to lipid compounds that exert diverse effects in the endocannabinoid system, such as regulating CB1 and CB2 receptor or moderating other bio-macromolecules within the endocannabinoid system. Some of the compounds showed improved receptor binding affinity, and/or improved receptor subtype selectivity, and improved bio-stability. Some of the compounds exhibit activities to regulate the enzymes that moderate the bio-disposal of endogenous cannabinoids, such as the fatty acid amide hydrolase (FAAH). Some of the compounds exhibit activities to inhibit the anandamide transporter. Other aspects of the invention are pharmaceutical preparations employing these ligands and methods of administering therapeutically effective amounts of the preparations to provide a physiological effect.

Abstract translation: 本公开的一个方面通常涉及在内源性大麻素系统中发挥不同作用的脂质化合物，例如调节CB1和CB2受体或调节内源性大麻素系统内的其他生物大分子。 一些化合物显示改善的受体结合亲和力，和/或改善的受体亚型选择性，以及改进的生物稳定性。 一些化合物表现出调节调节内源性大麻素的生物处理的酶的活性，例如脂肪酸酰胺水解酶（FAAH）。 一些化合物表现出抑制丙二胺转运蛋白的活性。 本发明的其它方面是使用这些配体的药物制剂和施用治疗有效量的制剂以提供生理作用的方法。

公开(公告)号：WO2004017922A2

公开(公告)日：2004-03-04

申请号：PCT/US2003/026609

申请日：2003-08-25

Applicant: UNIVERSITY OF CONNECTICUT

Inventor： MAKRIYANNIS, Alexandros ,  LU, Dai ,  LAI, Xin-Zhong

IPC: A61K

CPC classification number: A61K49/0052 ,  C07D311/80

Abstract: Novel tricyclic cannabinoid compounds are presented. Some of these compounds exhibit fluorescence properties. The fluorescent cannabinoid compounds are typically endogenously fluorescent. Some of these compounds, when administered in a therapeutically effective amount to an individual or animal, result in a sufficiently high level of that compound in the individual or animal to cause a physiological response. The physiological response useful to treat a number of physiological conditions.

Abstract translation: 提出了新的三环大麻素化合物。 其中一些化合物表现出荧光性质。 荧光大麻素化合物通常是内源荧光的。 这些化合物中的一些当以治疗有效量给予个体或动物时，导致该化合物在个体或动物中足够高的水平以引起生理反应。 对治疗许多生理状况有用的生理反应。

公开(公告)号：WO2004017920A2

公开(公告)日：2004-03-04

申请号：PCT/US2003/026585

申请日：2003-08-25

Applicant: UNIVERSITY OF CONNECTICUT

Inventor： MAKRIYANNIS, Alexandros ,  LAI, Xin-Zhong ,  LU, Dai

IPC: A61K

CPC classification number: C07D307/68 ,  C07C39/15 ,  C07C39/367 ,  C07C43/23 ,  C07C47/57 ,  C07C49/83 ,  C07C69/732 ,  C07C69/94 ,  C07C205/20 ,  C07C215/74 ,  C07C215/78 ,  C07C217/80 ,  C07C235/42 ,  C07C235/46 ,  C07C255/53 ,  C07D213/55

Abstract: Novel biphenyl and biphenyl-like cannabinoid compounds are presented. These compounds, when administered in a therapeutically effective amount to an individual or animal, result in a sufficiently high level of that compound in the individual or animal to cause a physiological response. The physiological response useful to treat a number of physiological conditions.

Abstract translation: 介绍了新颖的联苯和联苯类大麻素化合物。 这些化合物当以治疗有效量给予个体或动物时，导致个体或动物中该化合物的水平足够高以引起生理反应。 对治疗许多生理状况有用的生理反应。

公开(公告)号：WO2009051666A1

公开(公告)日：2009-04-23

申请号：PCT/US2008/011657

申请日：2008-10-10

Applicant: THE GOVERNMENT OF THE U.S.A. AS REPRESENTED BY THE SECRETARY OF THE DEPT. OF HEALTH& HUMAN SERVICES ,  UNIVERSITY OF CONNECTICUT ,  KUNOS, George ,  MAKRIYANNIS, Alexandros

Inventor： KUNOS, George ,  MAKRIYANNIS, Alexandros

IPC: C07C309/80 ,  A61P9/12 ,  A61P25/22 ,  A61P27/06

CPC classification number: C07C309/82

Abstract: Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid) and anandamide (an endogenous ligand for cannabinoid receptors). Disclosed herein are potent inhibitors of FAAH and methods for their use for treating a variety of disorder, including hypertension and cardiac hypertrophy.

Abstract translation: 脂肪酸酰胺水解酶（FAAH）是负责降解油酰胺（内源性睡眠诱导性脂质）和anandamide（大麻素受体的内源性配体）的酶。 本文公开了FAAH的有效抑制剂及其用于治疗多种障碍（包括高血压和心脏肥大）的方法。