公开(公告)号：US08211926B2

公开(公告)日：2012-07-03

申请号：US12816657

申请日：2010-06-16

Applicant: Robert Zhiyong Luo

Inventor： Robert Zhiyong Luo

IPC: A61K31/425 ,  A61K31/42 ,  A61K31/415 ,  A61K31/40 ,  A61K31/35 ,  C07D277/00 ,  C07D413/12 ,  C07D487/04 ,  C07D207/06 ,  C07D311/94

CPC classification number: C07D471/04 ,  C07D231/56 ,  C07D401/04 ,  C07D413/12 ,  C07D417/04 ,  C07D491/052

Abstract: The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.

Abstract translation: 本发明提供了具有式I的通式结构的取代的吡唑并 - 杂环。还提供式I化合物的药学上可接受的盐，酸式盐，水合物，溶剂化物和立体异构体。该化合物可用作大麻素受体的调节剂和预防 以及治疗大麻素受体相关疾病和病症，如疼痛，炎症和瘙痒。

公开(公告)号：US07842662B2

公开(公告)日：2010-11-30

申请号：US11938776

申请日：2007-11-12

Applicant: Claudio D. Schteingart ,  Frédérique Menzaghi ,  Guangcheng Jiang ,  Roberta Vezza Alexander ,  Javier Sueiras-Diaz ,  Robert H. Spencer ,  Derek T. Chalmers ,  Zhiyong Luo

Inventor： Claudio D. Schteingart ,  Frédérique Menzaghi ,  Guangcheng Jiang ,  Roberta Vezza Alexander ,  Javier Sueiras-Diaz ,  Robert H. Spencer ,  Derek T. Chalmers ,  Zhiyong Luo

IPC: A61K38/00

CPC classification number: C07K5/1016 ,  A61K38/00 ,  C07K5/1005 ,  C07K5/1008 ,  C07K5/1024 ,  C07K7/06

Abstract: The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.

Abstract translation: 本发明涉及κ阿片样物质受体的合成肽酰胺配体，特别是涉及低P450 CYP抑制和低渗透入脑的κ阿片受体激动剂。 本发明的合成肽酰胺符合以下结构：含有这些化合物的药物组合物可用于预防和治疗与各种疾病和病症相关的疼痛和炎症。 这种可治疗的疼痛包括内脏痛，神经性疼痛和痛觉过敏。 与IBD和IBS等条件相关的炎症，眼部和耳部炎症，其他疾病和病症如瘙痒症，水肿，低钠血症，低钾血症，肠梗阻，肠炎和青光眼均可用本发明的药物组合物治疗或预防。

公开(公告)号：US07737154B2

公开(公告)日：2010-06-15

申请号：US10596648

申请日：2004-12-20

Applicant: Zhiyong Luo ,  Deborah H Slee ,  John Williams

Inventor： Zhiyong Luo ,  Deborah H Slee ,  John Williams

IPC: C07D487/04 ,  A61K31/519 ,  A61P25/24 ,  A61P25/22

CPC classification number: C07D487/04

Abstract: CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure (I), including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, Y, Ar, and het are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

Abstract translation: 公开了CRF受体拮抗剂，其可用于治疗多种疾病，包括治疗在温血动物（例如中风）中表现出CRF分泌过高的病症。 本发明的CRF受体拮抗剂具有以下结构（I），其包括其立体异构体，前药和药学上可接受的盐，其中R1，R2，R3，Y，Ar和het如本文所定义。 还公开了含有CRF受体拮抗剂与药学上可接受的载体的组合物，以及其用途的方法。

公开(公告)号：US07727963B2

公开(公告)日：2010-06-01

申请号：US12176279

申请日：2008-07-18

Applicant: Claudio D. Schteingart ,  Guangcheng Jiang ,  Roberta Vezza Alexander ,  Javier Sueiras-Diaz ,  Zhiyong Luo

Inventor： Claudio D. Schteingart ,  Guangcheng Jiang ,  Roberta Vezza Alexander ,  Javier Sueiras-Diaz ,  Zhiyong Luo

IPC: A61K38/07

CPC classification number: C07K5/1016 ,  A61K38/00 ,  A61K38/07 ,  C07K5/10 ,  C07K5/1008 ,  C07K5/101 ,  C07K7/02

Abstract: The invention relates to synthetic tetrapeptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. An exemplary synthetic tetrapeptide amide of the invention is D-Phe-D-Phe-D-Leu-(ε-Me) D-Lys-[4-Amidinohomopiperazine amide]: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.

Abstract translation: 本发明涉及κ阿片样物质受体的合成四肽酰胺配体，特别涉及表现出低P450 CYP抑制和低渗透入脑的κ阿片受体激动剂。 本发明的示例性合成四肽酰胺是D-Phe-D-Phe-D-Leu-（α-Me）D-Lys- [4-脒基高密度哌嗪酰胺]：含有这些化合物的药物组合物可用于预防和治疗 与各种疾病和病症相关的疼痛和炎症。 这种可治疗的疼痛包括内脏痛，神经性疼痛和痛觉过敏。 与IBD和IBS等条件相关的炎症，眼部和耳部炎症，其他疾病和病症如瘙痒症，水肿，低钠血症，低钾血症，肠梗阻，肠炎和青光眼均可用本发明的药物组合物治疗或预防。

公开(公告)号：US20100075910A1

公开(公告)日：2010-03-25

申请号：US12480059

申请日：2009-06-08

Applicant: Claudio D. Schteingart ,  Frederique Menzaghi ,  Guangcheng Jiang ,  Roberta Vezza Alexander ,  Javier Sueiras-Diaz ,  Robert H. Spencer ,  Derek T. Chalmers ,  Zhiyong Luo

Inventor： Claudio D. Schteingart ,  Frederique Menzaghi ,  Guangcheng Jiang ,  Roberta Vezza Alexander ,  Javier Sueiras-Diaz ,  Robert H. Spencer ,  Derek T. Chalmers ,  Zhiyong Luo

IPC: A61K38/07 ,  C07K5/10 ,  A61P25/00 ,  A61P29/00 ,  A61P1/00 ,  A61P27/02

CPC classification number: C07K5/1016 ,  C07K7/02

Abstract: The invention relates to synthetic peptide amides that are ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: wherein Xaa is a D-amino acid and G is selected from the following three groups: The compounds are useful in the prophylaxis and treatment of pain, pruritus and inflammation associated with a variety of diseases and conditions.

Abstract translation: 本发明涉及作为κ阿片受体的配体的合成肽酰胺，特别是涉及低P450 CYP抑制和低渗透入脑的κ阿片样物质受体的激动剂。 本发明的合成肽酰胺符合以下结构：其中Xaa是D-氨基酸，G选自以下三组：所述化合物可用于预防和治疗与各种各样的相关的疼痛，瘙痒和炎症 疾病和病症。

公开(公告)号：US07576245B2

公开(公告)日：2009-08-18

申请号：US11338378

申请日：2006-01-24

Applicant: Wei Zhang ,  Zhiyong Luo

Inventor： Wei Zhang ,  Zhiyong Luo

IPC: C07C13/465

CPC classification number: C07D491/10 ,  C07B51/00 ,  C07B63/02 ,  C07C17/16 ,  C07C22/08 ,  C07C43/23 ,  C07C45/71 ,  C07C47/575 ,  C07C53/50 ,  C07C211/14 ,  C07C211/15 ,  C07C213/00 ,  C07C265/04 ,  C07C273/1827 ,  C07C311/16 ,  C07C323/20 ,  C07C335/16 ,  C07D207/46 ,  C07D209/14 ,  C07D209/16 ,  C07D211/62 ,  C07D213/74 ,  C07D217/04 ,  C07D217/06 ,  C07D231/38 ,  C07D265/26 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07C217/34 ,  C07C275/28

Abstract: The present invention includes methods and compositions for increasing the fluorous nature of an organic compound by reacting it with at least one fluorous compound to produce a fluorous tagged organic compound. The increased fluorous nature of the fluorous tagged organic compound can then be utilized to separate the fluorous organic compound from untagged reagents, reactants, catalysts and/or products derived therefrom. The resultant fluorous tagged organic compound can be subjected to subsequent chemical transformations, wherein the fluorous nature of the tagged compound is utilized to increase the ease of separation of the fluorous tagged organic compound from untagged reagents, reactants, catalysts and/or products derived therefrom, after each chemical transformation. The chemical transformations result in a second fluorous tagged organic compound wherein the fluorous nature of the second fluorous tagged organic compound can then be reduced by removing the fluorous group therefrom, thereby producing a second organic compound that may be employed as a pharmaceutical compound or intermediate, or a combinatorial library component.

Abstract translation: 本发明包括通过使其与至少一种氟化合物反应以产生氟标记的有机化合物来增加有机化合物的氟性质的方法和组合物。 然后可以利用氟标记的有机化合物的增加的氟性质将含氟有机化合物与未标记的试剂，反应物，催化剂和/或由其衍生的产物分离。 所得氟标记的有机化合物可以进行随后的化学转化，其中使用标记化合物的氟性质来增加氟标记的有机化合物与未标记的试剂，反应物，由其衍生的催化剂和/或产物的分离容易性， 每次化学转化后。 化学转化产生第二氟标记的有机化合物，其中可以通过从其中除去含氟基团来减少第二氟标记的有机化合物的氟性质，从而产生可用作药物化合物或中间体的第二有机化合物， 或组合库组件。

公开(公告)号：US20070293511A1

公开(公告)日：2007-12-20

申请号：US10596646

申请日：2004-12-20

Applicant: Zhiyong Luo ,  Deborah Slee ,  John Tellew ,  John Williams ,  Xiaohu Zahang

Inventor： Zhiyong Luo ,  Deborah Slee ,  John Tellew ,  John Williams ,  Xiaohu Zahang

IPC: A61K31/519 ,  A61P1/00 ,  A61P25/22 ,  A61P25/24 ,  A61P9/10 ,  C07D487/04

CPC classification number: C07D487/04

Abstract: CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, Y, Ar, and Het are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

Abstract translation: 公开了CRF受体拮抗剂，其可用于治疗各种疾病，包括治疗在温血动物（例如中风）中表现出CRF过度分泌的病症。 本发明的CRF受体拮抗剂具有以下结构：包括其立体异构体，前药和药学上可接受的盐，其中R 1，R 2，R 3， SUB，Y，Ar和Het如本文所定义。 还公开了含有CRF受体拮抗剂与药学上可接受的载体的组合物，以及其用途的方法。

公开(公告)号：US20070293508A1

公开(公告)日：2007-12-20

申请号：US10596651

申请日：2004-12-20

Applicant: John Williams ,  Zhiyong Luo ,  John Tellew

Inventor： John Williams ,  Zhiyong Luo ,  John Tellew

IPC: A61K31/4965 ,  A61P25/00 ,  C07D471/00

CPC classification number: C07D471/16

Abstract: CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders in mammals, including the treatment of disorders, such as stroke, manifesting hypersecretion of CRF. The CRF receptor antagonists of this invention have the following structure: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein R1, R2, R5, Ar, and Het are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

Abstract translation: 公开了CRF受体拮抗剂，其可用于治疗哺乳动物中的各种疾病，包括治疗诸如中风的疾病，表现出CRF的过度分泌。 本发明的CRF受体拮抗剂具有以下结构：包括其立体异构体，前药和药学上可接受的盐，其中R 1，R 2，R 5， SUB，Ar和Het如本文所定义。 还公开了含有CRF受体拮抗剂与药学上可接受的载体的组合物，以及其用途的方法。

公开(公告)号：US07214819B2

公开(公告)日：2007-05-08

申请号：US10442664

申请日：2003-05-21

Applicant: Dennis Patrick Curran ,  Zhiyong Luo

Inventor： Dennis Patrick Curran ,  Zhiyong Luo

IPC: C07B57/00

CPC classification number: C07D207/333 ,  C07B37/04 ,  C07B61/00 ,  C07B63/00 ,  C07C1/325 ,  C07C17/02 ,  C07C45/46 ,  C07D307/46 ,  C07D333/22 ,  C07C15/52 ,  C07C23/10 ,  C07C22/04 ,  C07C49/84

Abstract: A method of obtaining an enantioenriched organic compound comprising the steps of: 1) generating from a starting racemic, non-enantiopure or achiral compound a first mixture comprising at least one fluorous-tagged compound and at least one other non-fluorous tagged compound, at least one of these two compounds being enantioenriched relative to the starting compound; 2) contacting a first non-fluorous phase including the first mixture with a fluorous phase at a first phase interface, the fluorous-tagged compound distributing between the first non-fluorous phase and the fluorous phase; and 3) contacting the fluorous phase with a second non-fluorous phase at a second phase interface. The method further includes the step of having a third compound in the second non-fluorous phase that reacts with the fluorous-tagged compound to produce a second compound and the step of generating the first mixture by chemical or enzymatic kinetic resolution of a racemic or non-enantiopure compound.

Abstract translation: 一种获得对映体有机化合物的方法，包括以下步骤：1）从起始外消旋非对映体纯或非手性化合物产生包含至少一种含氟标记化合物和至少一种其它非氟标记化合物的第一混合物， 这两种化合物中的至少一种相对于起始化合物具有对映体; 2）在第一相界面处将包含第一混合物的第一非氟相与氟相接触，分配在第一非氟相和氟相之间的含氟标记化合物; 和3）在第二相界面处将氟相与第二非氟相接触。 所述方法还包括使所述第二非氟相中的第三化合物与所述含氟标记的化合物反应以产生第二化合物的步骤，以及通过化学或酶动力学拆分外消旋或非 - - 昂贵化合物。

公开(公告)号：US20050096478A1

公开(公告)日：2005-05-05

申请号：US10999698

申请日：2004-11-29

Applicant: Dennis Curran ,  Roger Read ,  Zhiyong Luo

Inventor： Dennis Curran ,  Roger Read ,  Zhiyong Luo

IPC: C07C69/96 ,  C07C237/22 ,  C07C237/42 ,  C07C247/20 ,  C07C255/61 ,  C07C255/62 ,  C07C269/04 ,  C07C271/08 ,  C07D207/14 ,  C07D207/16 ,  C07D211/62 ,  C07D213/40 ,  C07D217/06 ,  C07D401/06 ,  C07D405/06 ,  C07F7/04

CPC classification number: C07D213/40 ,  C07C69/96 ,  C07C237/22 ,  C07C237/42 ,  C07C255/62 ,  C07D207/14 ,  C07D207/16 ,  C07D211/62 ,  C07D217/06 ,  C07D401/06 ,  C07D405/06 ,  Y10T436/13 ,  Y10T436/19

Abstract: A method of increasing the fluorous nature of a compound includes the step of reacting the compound with at least one second compound having the formula: wherein Rf is a fluorous group, Rs is a spacer group, d is 1 or 0, m is 1, 2 or 3, Ra is an alkyl group and X is a suitable leaving group. A compound has the formula: wherein Rf is a fluorous group, n is an integer between 0 and 6, m is 1, 2 or 3, Ra is an alkyl group and X is a leaving group.

Abstract translation: 增加化合物的氟性质的方法包括使化合物与至少一种具有下式的第二化合物反应的步骤：其中Rf是氟基，Rs是间隔基，d是1或0，m是1， 2或3，Ra是烷基，X是合适的离去基团。 化合物具有下式：其中Rf是氟基，n是0和6之间的整数，m是1,2或3，Ra是烷基，X是离去基团。