CN107108468B - 赖氨酸牙龈卟啉菌蛋白酶的抑制剂 - Google Patents

赖氨酸牙龈卟啉菌蛋白酶的抑制剂 Download PDF

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CN107108468B
CN107108468B CN201580062146.1A CN201580062146A CN107108468B CN 107108468 B CN107108468 B CN 107108468B CN 201580062146 A CN201580062146 A CN 201580062146A CN 107108468 B CN107108468 B CN 107108468B
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carbonyl
disease
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pharmaceutically acceptable
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CN107108468A (zh
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安德烈·康拉迪
史蒂芬·S·多米尼
林奇 凯西·克劳福德
克雷格·科伯恩
约瑟夫·瓦卡
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Lighthouse Pharma Inc
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Cortexyme Inc
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CN201580062146.1A 2014-10-06 2015-10-05 赖氨酸牙龈卟啉菌蛋白酶的抑制剂 Expired - Fee Related CN107108468B (zh)

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Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016057413A2 (en) 2014-10-06 2016-04-14 Cortexyme, Inc. Inhibitors of lysine gingipain
CA3004095A1 (en) 2015-11-09 2017-05-18 Cortexyme, Inc. Inhibitors of arginine gingipain
WO2017201322A1 (en) * 2016-05-19 2017-11-23 Cortexyme, Inc. Treatment of osteoarthritis with gingipain blocking agents
EP4480541A3 (en) 2016-09-16 2025-04-30 Lighthouse Pharmaceuticals, Inc. Ketone inhibitors of lysine gingipain
WO2018209132A1 (en) * 2017-05-10 2018-11-15 Cortexyme, Inc. Aminopyridine compounds and methods for the preparation and use thereof
US20210355527A1 (en) * 2018-09-27 2021-11-18 Cortexyme, Inc. Methods for detection of microbial nucleic acids in body fluids
US20240400654A1 (en) * 2020-11-03 2024-12-05 Keystone Bio, Inc. Antigen-binding molecules that bind to porphyromonas gingivalis
KR102779135B1 (ko) * 2023-06-19 2025-03-12 한국과학기술연구원 신규한 형광 화합물 및 이를 이용한 진지페인 검출용 조성물, 포르피로모나스 진지발리스 감염 진단용 조성물 또는 포르피로모나스 진지발리스에 대한 항균용 조성물
CN119912460A (zh) * 2025-03-31 2025-05-02 上海光声制药有限公司 卟啉衍生物、其制备方法及其用于抑菌的用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1202902A (zh) * 1995-11-03 1998-12-23 阿克佐诺贝尔公司 凝血酶抑制剂
CN1353701A (zh) * 1999-01-27 2002-06-12 奥索-麦克尼尔药品公司 用作类胰蛋白酶抑制剂的肽基杂环酮类化合物

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU600226B2 (en) 1985-02-04 1990-08-09 Merrell Pharmaceuticals Inc. Novel peptidase inhibitors
US5055451A (en) 1986-12-22 1991-10-08 Syntex Inc. Aryloxy and arylacyloxy methyl ketones as thiol protease inhibitors
JPH01163162A (ja) * 1987-12-18 1989-06-27 Showa Denko Kk アミノ酸誘導体および酵素阻害剤
US5451410A (en) * 1993-04-22 1995-09-19 Emisphere Technologies, Inc. Modified amino acids for encapsulating active agents
GB9019558D0 (en) 1990-09-07 1990-10-24 Szelke Michael Enzyme inhibitors
WO1993000926A1 (en) 1991-07-02 1993-01-21 Children's Medical Center Corporation Treatment of periodontal disease with protease inhibitors
SE9102462D0 (sv) 1991-08-28 1991-08-28 Astra Ab New isosteric peptides
US5374623A (en) 1992-08-20 1994-12-20 Prototek, Inc. Cysteine protease inhibitors effective for in vivo use
WO1996019483A1 (en) 1994-12-22 1996-06-27 Biochem Pharma Inc. Low molecular weight bicyclic thrombin inhibitors
AU713530B2 (en) 1995-03-24 1999-12-02 Molecumetics, Ltd. Beta-sheet mimetics and use thereof as protease inhibitors
WO1996030396A1 (en) 1995-03-24 1996-10-03 Molecumetics Ltd. β-SHEET MIMETICS AND USE THEREOF AS PROTEASE INHIBITORS
GB9510264D0 (en) 1995-05-22 1995-07-19 Iaf Biochem Int Low molecular weight bicyclic-urea type thrombin inhibitors
US5827866A (en) 1995-06-07 1998-10-27 Ortho Pharmaceutical Corporation Peptidyl heterocycles useful in the treatment of thrombin related disorders
US5523308A (en) 1995-06-07 1996-06-04 Costanzo; Michael J. Peptidyl heterocycles useful in the treatment of thrombin related disorders
US5827860A (en) 1995-06-07 1998-10-27 Ortho Pharmaceutical Corporation Peptidyl heterocycles useful in the treatment of thrombin related disorders
ES2262184T3 (es) 1996-08-05 2006-11-16 Myriad Genetics, Inc. Utilizacion de mimeticos de hojas beta como inhibidores de proteasa y de kinasa o como inhibidores de factores de transcripcion.
WO1998009987A1 (en) 1996-09-06 1998-03-12 Biochem Pharma, Inc. Lactam inhibitors of thrombin
WO1999026925A1 (en) 1997-11-26 1999-06-03 Yoshitomi Pharmaceutical Industries, Ltd. Tryptase inhibitors comprising heterocyclic amide compounds
WO1999041276A1 (en) 1998-02-12 1999-08-19 Molecumetics Ltd. β-SHEET MIMETICS AND METHODS RELATING TO THE USE THEREOF
US6323219B1 (en) 1998-04-02 2001-11-27 Ortho-Mcneil Pharmaceutical, Inc. Methods for treating immunomediated inflammatory disorders
US7053056B2 (en) * 1998-07-02 2006-05-30 Idun Pharmaceuticals, Inc. C-terminal modified oxamyl dipeptides as inhibitors of the ICE/ced-3 family of cysteine proteases
WO2000044731A1 (en) * 1999-01-27 2000-08-03 G.D. Searle & Co. Novel hydroxyamidino carboxylate derivatives useful as nitric oxide synthase inhibitors
JP2002539190A (ja) 1999-03-15 2002-11-19 アクシス・ファーマシューティカルズ・インコーポレイテッド プロテアーゼ阻害剤としての新規化合物および組成物
US6790989B2 (en) * 2000-01-13 2004-09-14 Idun Pharmaceuticals, Inc. Inhibitors of the ICE/ced-3 family of cysteine proteases
US7205384B2 (en) 2003-08-05 2007-04-17 Ortho-Mcneil Pharmaceutical Inc. Process for preparing peptidyl heterocyclic ketone derivatives
US8263563B2 (en) 2004-07-23 2012-09-11 Robert E. Smith Furin inhibitors
RU2419626C2 (ru) * 2006-05-23 2011-05-27 Айрм Ллк Соединения и композиции в качестве ингибиторов протеазы, активирующей каналы
EP2262783A2 (en) * 2008-02-21 2010-12-22 Sanofi-Aventis Covalently binding imaging probes
AU2013305759C1 (en) * 2012-08-23 2018-01-18 Janssen Biopharma, Inc. Compounds for the treatment of paramoxyvirus viral infections
WO2014145257A2 (en) 2013-03-15 2014-09-18 The Board Of Trustees Of The Leland Stanford Junior University Activity-based probe compounds, compositions, and methods of use
WO2016057413A2 (en) 2014-10-06 2016-04-14 Cortexyme, Inc. Inhibitors of lysine gingipain

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1202902A (zh) * 1995-11-03 1998-12-23 阿克佐诺贝尔公司 凝血酶抑制剂
CN1353701A (zh) * 1999-01-27 2002-06-12 奥索-麦克尼尔药品公司 用作类胰蛋白酶抑制剂的肽基杂环酮类化合物

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
M.A.Curtis et al..Attenuation of the Virulence of Porphyromonas gingivalis by Using a Specific Synthetic Kgp Protease Inhibitor.《INFECTIONAND IMMUNITY》.2002,第70卷(第12期),6968–6975. *
Unique Overlap in the Prerequisites for Thrombin Inhibition and Oral Bioavailability Resulting in Potent Oral Antithrombotics;Anton E.P.Adang et al.;《J.Med.Chem.》;20020830;4419-4432 *

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