公开(公告)号：US20100041880A1

公开(公告)日：2010-02-18

申请号：US12541352

申请日：2009-08-14

Applicant: Daniel P. Becker ,  Andria M. Panagopoulos ,  Marlon R. Lutz, JR.

Inventor： Daniel P. Becker ,  Andria M. Panagopoulos ,  Marlon R. Lutz, JR.

IPC: C07D255/04

CPC classification number: C07D255/04 ,  C07D487/18

Abstract: Tribenzo-1,4,7-triazacyclononane and derivatives thereof having a formula (I) are disclosed. Methods of making tribenzo-1,4,7-triazacyclononane and related compounds also are disclosed.

Abstract translation: 公开了具有式（I）的三苯并-1,3,7-三氮杂环壬烷及其衍生物。 还公开了制备三苯并-1,4,7-三氮杂环壬烷及相关化合物的方法。

公开(公告)号：US06890937B2

公开(公告)日：2005-05-10

申请号：US10337942

申请日：2003-01-07

Applicant: Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Terri L. Boehm ,  Jeffery N. Carroll ,  Gary A. DeCrezcenzo ,  Theresa R. Fletcher ,  John N. Freskos ,  Daniel P. Getman ,  Gunnar J. Hanson ,  Susan L. Hockerman ,  Carol P. Howard ,  Stephen A. Kolodziej ,  Madeleine H. Li ,  Joseph J. McDonald ,  Deborah A. Mischke ,  Patrick B. Mullins ,  Joseph G. Rico ,  Nathan W. Stehle ,  Clara I. Villamil

Inventor： Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Terri L. Boehm ,  Jeffery N. Carroll ,  Gary A. DeCrezcenzo ,  Theresa R. Fletcher ,  John N. Freskos ,  Daniel P. Getman ,  Gunnar J. Hanson ,  Susan L. Hockerman ,  Carol P. Howard ,  Stephen A. Kolodziej ,  Madeleine H. Li ,  Joseph J. McDonald ,  Deborah A. Mischke ,  Patrick B. Mullins ,  Joseph G. Rico ,  Nathan W. Stehle ,  Clara I. Villamil

IPC: A61K31/16 ,  A61K31/167 ,  A61K31/27 ,  A61K31/35 ,  A61K31/351 ,  A61K31/357 ,  A61K31/366 ,  A61K31/38 ,  A61K31/381 ,  A61K31/382 ,  A61K31/39 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/444 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4525 ,  A61K31/454 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5375 ,  A61K31/54 ,  A61K31/541 ,  A61P1/02 ,  A61P1/04 ,  A61P9/10 ,  A61P13/00 ,  A61P19/00 ,  A61P19/02 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P35/04 ,  A61P43/00 ,  C07C317/44 ,  C07C319/06 ,  C07D211/66 ,  C07D211/94 ,  C07D211/96 ,  C07D239/04 ,  C07D279/06 ,  C07D309/08 ,  C07D309/12 ,  C07D319/06 ,  C07D327/02 ,  C07D333/38 ,  C07D335/02 ,  C07D337/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D521/00 ,  C07D211/06

CPC classification number: C07D231/12 ,  A61K31/19 ,  A61K31/4166 ,  A61K31/421 ,  A61K31/426 ,  C07C317/44 ,  C07D207/48 ,  C07D211/54 ,  C07D211/66 ,  C07D211/86 ,  C07D211/94 ,  C07D211/96 ,  C07D225/02 ,  C07D233/56 ,  C07D239/04 ,  C07D249/08 ,  C07D263/06 ,  C07D265/06 ,  C07D279/06 ,  C07D281/08 ,  C07D309/08 ,  C07D309/28 ,  C07D319/06 ,  C07D325/00 ,  C07D335/02 ,  C07D337/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9, and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. The administered enzyme inhibitor corresponds in structure to formula (I), below, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are both hydrido or R1 and R2 together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two, or three heteroatoms in the ring that are oxygen, sulfur, or nitrogen. R3 in formula (I) is an optionally substituted aryl or optionally substituted heteroaryl radical. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.

Abstract translation: 公开了一种处理方法，其包括施用有效量的显示出一种或多种基质金属蛋白酶（MMP）酶如MMP-2，MMP-9和MMP-13的优异抑制活性的芳香族砜异羟肟酸，同时显示 至少对具有与病理基质金属蛋白酶活性相关的病症的宿主的MMP-1的抑制显着降低。 施用的酶抑制剂在结构上对应于下式（I）或其药学上可接受的盐，其中R 1和R 2都是氢或R 2， 1和R 2与它们所键合的原子一起形成在环中含有一个，两个或三个杂原子的5-至8-元环，其为氧，硫， 或氮气。 式（I）中的R 3是任选取代的芳基或任选取代的杂芳基。 还公开了具有这些选择活性的金属蛋白酶抑制剂化合物，制备这种化合物的方法和使用抑制剂的药物组合物。

公开(公告)号：US06890928B2

公开(公告)日：2005-05-10

申请号：US10657034

申请日：2003-09-05

Applicant: John N. Freskos ,  Yvette M. Fobian ,  Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Terri L. Boehm ,  Jeffrey N. Carroll ,  Gary A. DeCrescenzo ,  Susan L. Hockerman ,  Darren J. Kassab ,  Steve A. Kolodziej ,  Joseph McDonald ,  Deborah A. Mischke ,  Monica B. Norton ,  Joseph G. Rico ,  John J. Talley ,  Clara I. Villamil ,  Lijuan Jane Wang

Inventor： John N. Freskos ,  Yvette M. Fobian ,  Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Terri L. Boehm ,  Jeffrey N. Carroll ,  Gary A. DeCrescenzo ,  Susan L. Hockerman ,  Darren J. Kassab ,  Steve A. Kolodziej ,  Joseph McDonald ,  Deborah A. Mischke ,  Monica B. Norton ,  Joseph G. Rico ,  John J. Talley ,  Clara I. Villamil ,  Lijuan Jane Wang

IPC: C07D491/048 ,  A61K31/35 ,  A61K31/351 ,  A61K31/357 ,  A61K31/381 ,  A61K31/397 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/41 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/42 ,  A61K31/423 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/428 ,  A61K31/4355 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/453 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/455 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/506 ,  A61K31/53 ,  A61K31/5377 ,  A61P1/02 ,  A61P1/04 ,  A61P1/16 ,  A61P7/00 ,  A61P7/02 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P13/12 ,  A61P17/02 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P25/00 ,  A61P25/18 ,  A61P25/28 ,  A61P27/02 ,  A61P27/16 ,  A61P29/00 ,  A61P31/04 ,  A61P35/00 ,  A61P35/04 ,  A61P37/02 ,  A61P37/06 ,  A61P39/00 ,  A61P43/00 ,  C07D211/66 ,  C07D309/08 ,  C07D309/12 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D401/02

CPC classification number: C07D401/12 ,  A61K31/351 ,  A61K31/41 ,  A61K31/453 ,  A61K31/454 ,  C04B35/632 ,  C07D211/66 ,  C07D309/08 ,  C07D309/12 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  Y02A50/411

Abstract: This invention is directed to aromatic sulfone hydroxamic acids (including hydroxamates) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

Abstract translation: 本发明涉及特别是抑制基质金属蛋白酶（也称为“基质金属蛋白酶”或“MMP”）活性和/或软骨聚集蛋白聚糖酶活性的芳香族砜异羟肟酸（包括异羟肟酸盐）及其盐。 本发明还涉及一种预防或治疗方法，其包括将有效量的MMP抑制和/或聚集蛋白聚糖蛋白酶抑制剂的这种化合物或盐施用于动物，特别是哺乳动物，所述动物特别是哺乳动物具有（或处置）具有相关的病理状态 具有MMP和/或蛋白聚糖蛋白聚糖酶活性。

公开(公告)号：US06689794B2

公开(公告)日：2004-02-10

申请号：US10142737

申请日：2002-05-10

Applicant: John N. Freskos ,  Yvette M. Fobian ,  Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Terri L. Boehm ,  Jeffery N. Carroll ,  Gary A. DeCrescenzo ,  Susan L. Hockerman ,  Darren J. Kassab ,  Steve A. Kolodziej ,  Joseph McDonald ,  Deborah A. Mischke ,  Monica B. Norton ,  Joseph G. Rico ,  John J. Talley ,  Clara I. Villamil ,  Lijuan Jane Wang

Inventor： John N. Freskos ,  Yvette M. Fobian ,  Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Terri L. Boehm ,  Jeffery N. Carroll ,  Gary A. DeCrescenzo ,  Susan L. Hockerman ,  Darren J. Kassab ,  Steve A. Kolodziej ,  Joseph McDonald ,  Deborah A. Mischke ,  Monica B. Norton ,  Joseph G. Rico ,  John J. Talley ,  Clara I. Villamil ,  Lijuan Jane Wang

IPC: A61K31445

CPC classification number: C07D401/12 ,  A61K31/351 ,  A61K31/41 ,  A61K31/453 ,  A61K31/454 ,  C04B35/632 ,  C07D211/66 ,  C07D309/08 ,  C07D309/12 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  Y02A50/411

Abstract: This invention is directed to aromatic sulfone hydroxamates (also known as “aromatic sulfone hydroxamic acids”) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

公开(公告)号：US06476027B1

公开(公告)日：2002-11-05

申请号：US09254531

申请日：1999-12-06

Applicant: Clara I. Villamil ,  John N. Freskos ,  Brent V. Mischke ,  Patrick B. Mullins ,  Robert M. Heintz ,  Daniel P. Getman ,  Joseph J. McDonald ,  Gary A. DeCrescenzo ,  Thomas E. Barta ,  Daniel P. Becker

Inventor： Clara I. Villamil ,  John N. Freskos ,  Brent V. Mischke ,  Patrick B. Mullins ,  Robert M. Heintz ,  Daniel P. Getman ,  Joseph J. McDonald ,  Gary A. DeCrescenzo ,  Thomas E. Barta ,  Daniel P. Becker

IPC: A61K3116

CPC classification number: C07D213/30 ,  C07C317/22 ,  C07C317/44 ,  C07C323/65 ,  C07D207/16 ,  C07D211/62 ,  C07D213/82 ,  C07D295/15

Abstract: An N-hydroxy sulfonyl butanamide compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated N-hydroxy sulfonyl butanamide compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

Abstract translation: 公开了包括抑制基质金属蛋白酶活性的N-羟基磺酰基丁酰胺化合物，其处理方法包括将具有MMP酶抑制有效量的预期N-羟基磺酰基丁酰胺化合物施用于具有与病理基质相关的病症的宿主 金属蛋白酶活性。

公开(公告)号：US5591749A

公开(公告)日：1997-01-07

申请号：US424934

申请日：1995-04-19

Applicant: Daniel P. Becker ,  Daniel L. Flynn ,  Alan E. Moormann ,  Roger Nosal ,  Clara I. Villamil

Inventor： Daniel P. Becker ,  Daniel L. Flynn ,  Alan E. Moormann ,  Roger Nosal ,  Clara I. Villamil

IPC: A61K31/40 ,  A61K31/435 ,  A61K31/445 ,  A61K31/4468 ,  A61K31/46 ,  A61P43/00 ,  C07C219/12 ,  C07C233/62 ,  C07D211/46 ,  C07D211/58 ,  C07D451/04 ,  C07D451/06 ,  C07D451/14 ,  C07D453/02 ,  C07D471/04 ,  C07D471/06 ,  C07D471/22 ,  C07D487/04 ,  C07D487/08 ,  C07D519/00 ,  A61K31/44

CPC classification number: C07D471/04

Abstract: The imidazopyridines compounds of the present invention are serotonergic 5-HT.sub.3 antagonists. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and withdrawal, gastrointestinal motility disturbances (including esophageal reflux, dyspepsia, gastric stasis, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

Abstract translation: 本发明的咪唑并吡啶化合物是5-羟色胺能5-HT 3拮抗剂。 因此，它们可用于治疗其中5-HT 3受体拮抗作用有益的人和动物。 治疗指示但不限于治疗焦虑，精神病，抑郁症（特别是伴有焦虑的抑郁症），认知障碍，药物滥用依赖和戒断，胃肠蠕动障碍（包括食管反流，消化不良，胃潴留，肠易激综合征 综合征），化疗引起的呕吐和内脏痛。 此外，本发明的化合物可以用作生物活性化合物的鼻吸收增强剂。

公开(公告)号：US5521193A

公开(公告)日：1996-05-28

申请号：US445057

申请日：1995-05-19

Applicant: Daniel L. Flynn ,  Alan E. Moormann ,  Daniel P. Becker ,  Michael S. Dappen ,  Roger Nosal ,  Robert L. Shone ,  Clara I. Villamil

Inventor： Daniel L. Flynn ,  Alan E. Moormann ,  Daniel P. Becker ,  Michael S. Dappen ,  Roger Nosal ,  Robert L. Shone ,  Clara I. Villamil

IPC: C07D403/12 ,  C07D471/18 ,  C07D487/04 ,  C07D487/08 ,  A61K31/395 ,  C07D221/02

CPC classification number: C07D403/12 ,  C07D487/04 ,  C07D487/08

Abstract: This invention relates to compounds useful in treating HT.sub.4 and/or HT.sub.3 mediated, conditions of the formula ##STR1## or a pharmaceutically acceptable salt thereof.

Abstract translation: 本发明涉及可用于治疗HT4和/或HT3介导的下式的化合物或其药学上可接受的盐的化合物。

公开(公告)号：US5399562A

公开(公告)日：1995-03-21

申请号：US191840

申请日：1994-02-04

Applicant: Daniel P. Becker ,  Daniel L. Flynn ,  Clara I. Villamil

Inventor： Daniel P. Becker ,  Daniel L. Flynn ,  Clara I. Villamil

IPC: C07D451/04 ,  C07D451/06 ,  C07D453/02 ,  C07D471/18 ,  C07D487/04 ,  C07D487/10 ,  A61K31/44 ,  C07D453/00

CPC classification number: C07D451/04 ,  C07D451/06 ,  C07D453/02 ,  C07D487/04 ,  C07D487/10

Abstract: This invention relates to compounds of the formula: ##STR1## which are useful as 5-HT.sub.4 agonists or antagonists and 5-HT.sub.3 antagonists.

Abstract translation: 本发明涉及可用作5-HT4激动剂或拮抗剂和5-HT 3拮抗剂的下式的化合物：。

公开(公告)号：US5260303A

公开(公告)日：1993-11-09

申请号：US666113

申请日：1991-03-07

Applicant: Daniel P. Becker ,  Daniel L. Flynn ,  Alan E. Moormann ,  Roger Nosal ,  Clara I. Villamil

Inventor： Daniel P. Becker ,  Daniel L. Flynn ,  Alan E. Moormann ,  Roger Nosal ,  Clara I. Villamil

IPC: A61K31/40 ,  A61K31/435 ,  A61K31/445 ,  A61K31/4468 ,  A61K31/46 ,  A61P43/00 ,  C07C219/12 ,  C07C233/62 ,  C07D211/46 ,  C07D211/58 ,  C07D451/04 ,  C07D451/06 ,  C07D451/14 ,  C07D453/02 ,  C07D471/04 ,  C07D471/06 ,  C07D471/22 ,  C07D487/04 ,  C07D487/08 ,  C07D519/00 ,  C07D453/06

CPC classification number: C07D471/04

Abstract: The imidazopyridines compounds of the present invention are serotonergic 5-HT.sub.3 antagonists. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and withdrawal, gastrointestinal motility disturbancies (including esophageal reflux, dyspepsia, gastric stasis, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

Abstract translation: 本发明的咪唑并吡啶化合物是5-羟色胺能5-HT 3拮抗剂。 因此，它们可用于治疗其中5-HT 3受体拮抗作用有益的人和动物。 治疗指示但不限于治疗焦虑，精神病，抑郁症（特别是伴有焦虑症的抑郁症），认知障碍，药物滥用依赖和戒断，胃肠蠕动窒息（包括食管反流，消化不良，胃潴留，肠易激惹） 综合征），化疗引起的呕吐和内脏痛。 此外，本发明的化合物可以用作生物活性化合物的鼻吸收增强剂。

公开(公告)号：US5219850A

公开(公告)日：1993-06-15

申请号：US896281

申请日：1992-06-10

Applicant: Daniel P. Becker ,  Daniel L. Flynn ,  Alan E. Moormann ,  Roger Nosal ,  Clara I. Villamil

Inventor： Daniel P. Becker ,  Daniel L. Flynn ,  Alan E. Moormann ,  Roger Nosal ,  Clara I. Villamil

IPC: C07D519/00

CPC classification number: C07D519/00

Abstract: The imidazopyridines containing meso-azacycle side chains as described herein find utility as antagonists of the serotonin 5-HT.sub.3 receptor. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and/or withdrawal, gastrointestinal motility disturbancies (including esophageal reflux, dyspepsia, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

Abstract translation: 含有本文所述的内消旋 - 侧链侧链的咪唑并吡啶可用作5-羟色胺5-HT 3受体的拮抗剂。 因此，它们可用于治疗其中5-HT 3受体的拮抗作用有益的人和动物。 治疗指示但不限于治疗焦虑症，精神病，抑郁症（特别是伴有焦虑症的抑郁症），认知障碍，药物滥用依赖和/或戒断，胃肠蠕动性窒息（包括食管反流，消化不良，肠易激综合征 ），由化疗药引起的呕吐和内脏痛。 此外，本发明的化合物可以用作生物活性化合物的鼻吸收增强剂。