SG11201900947RA - Tlr7/8 antagonists and uses thereof - Google Patents

Tlr7/8 antagonists and uses thereof

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Publication number
SG11201900947RA
SG11201900947RA SG11201900947RA SG11201900947RA SG11201900947RA SG 11201900947R A SG11201900947R A SG 11201900947RA SG 11201900947R A SG11201900947R A SG 11201900947RA SG 11201900947R A SG11201900947R A SG 11201900947RA SG 11201900947R A SG11201900947R A SG 11201900947RA
Authority
SG
Singapore
Prior art keywords
international
massachusetts
pct
tlr7
antagonists
Prior art date
Application number
SG11201900947RA
Inventor
Brian A Sherer
Xiaoling Chen
Esther Cleary
Nadia Brugger
Original Assignee
Merck Patent Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh
Publication of SG11201900947RA publication Critical patent/SG11201900947RA/en

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    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
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Abstract

Title: TLR7/8 ANTAGONISTS AND USES THEREOF (57) : The present invention relates to compounds of Formula I and pharmaceutically ac- ceptable compositions thereof, useful as TLR7/8 antagonists. X , y (R 4 ), (R3)p W O 20 18/03 143 4 Al PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) ~~ll~~~~~~~~ 011101VIIIVIIIVIII olo oui olo mil Immo ow (10) International Publication Number WO 2018/031434 Al WIPO I PCT (12) INTERNATIONAL APPLICATION (19) World Intellectual Property Organization International Bureau (43) International Publication Date 15 February 2018 (15.02.2018) (51) International Patent Classification: C07D 401/14 (2006.01) C07D 241/42 (2006.01) C07D 215/14 (2006.01) C07D 451/02 (2006.01) C07D 215/18 (2006.01) C07D 471/04 (2006.01) C07D 401/04 (2006.01) C07D 471/08 (2006.01) C07D 401/12 (2006.01) CO7D 471/10 (2006.01) C07D 413/04 (2006.01) CO7D 487/04 (2006.01) (21) International Application Number: PCT/US2017/045671 (22) International Filing Date: 07 August 2017 (07.08.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/371,917 08 August 2016 (08.08.2016) US (71) Applicant: MERCK PATENT GMBH [DE/DE]; Frank- furter Strasse 250, 64293 Darmstadt (DE). (72) Inventors; and = (71) Applicants (for US only): SHERER, Brian A. [US/US]; 57 Harris Road, Nashua, New Hampshire 03062 (US). CHEN, Xiaoling [CA/US]; 250 Hammond Pond Pkwy, U9065, Chestnut Hill, Massachusetts 02467 (US). CLEARY, Es- ther [US/US]; 22 Murdock Street, Somerville, Massachu- setts 02145 (US). BRUGGER, Nadia [CH/US]; 7 Haskell Street, Cambridge, Massachusetts 02140 (US). (74) Agent: KIM, Dwight D.; EMD Serono Research and Development Institute, One Technology Place, Rockland, Massachusetts 02370 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3))
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Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2021006804A (en) 2015-12-17 2023-01-13 Merck Patent Gmbh Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders.
WO2018031434A1 (en) 2016-08-08 2018-02-15 Merck Patent Gmbh Tlr7/8 antagonists and uses thereof
FI3526323T3 (en) 2016-10-14 2023-06-06 Prec Biosciences Inc Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
WO2018089695A1 (en) * 2016-11-11 2018-05-17 Dynavax Technologies Corporation Toll-like receptor antagonist compounds and methods of use
WO2019125849A1 (en) 2017-12-19 2019-06-27 Merck Patent Gmbh Tlr7/8 antagonists and uses thereof
EP3728282B1 (en) 2017-12-20 2023-11-22 Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. 2'3' cyclic dinucleotides with phosphonate bond activating the sting adaptor protein
CN111566120B (en) 2017-12-20 2023-09-29 捷克共和国有机化学与生物化学研究所 3' cyclic dinucleotides with phosphonate bonds of activated STING adaptor protein
JP7328977B2 (en) 2018-02-12 2023-08-17 エフ． ホフマン－ラ ロシュ アーゲー Novel sulfone compounds and derivatives for the treatment and prevention of viral infections
TWI818007B (en) 2018-04-06 2023-10-11 捷克科學院有機化學與生物化學研究所 2'3'-cyclic dinucleotides
TWI833744B (en) 2018-04-06 2024-03-01 捷克科學院有機化學與生物化學研究所 3'3'-cyclic dinucleotides
US11142750B2 (en) 2018-04-12 2021-10-12 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome
PE20210131A1 (en) * 2018-06-05 2021-01-19 Hoffmann La Roche TETRAHYDRO-1H-PIRAZINE [2,1-a] ISOINDOLYLQUINOLINE COMPOUNDS FOR THE TREATMENT OF AUTOIMMUNE DISEASES
WO2019238616A1 (en) 2018-06-12 2019-12-19 F. Hoffmann-La Roche Ag Novel heteroaryl heterocyclyl compounds for the treatment of autoimmune disease
EP3826724B1 (en) 2018-07-23 2022-10-05 F. Hoffmann-La Roche AG Novel piperazine compounds for the treatment of autoimmune disease
CN112638908A (en) 2018-09-04 2021-04-09 豪夫迈·罗氏有限公司 Benzothiazoles for treatment of autoimmune diseases
JP2022502353A (en) 2018-09-06 2022-01-11 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft A novel cyclic amidine compound for the treatment of autoimmune disorders
CN113271938A (en) * 2018-11-30 2021-08-17 林伯士拉克许米公司 TYK2 inhibitors and uses thereof
US20230015242A1 (en) * 2019-11-19 2023-01-19 Hoffmann-La Roche Inc. Triazatricycle compounds for the treatment of autoimmune disease
US20230219959A1 (en) * 2019-11-19 2023-07-13 Hoffmann-La Roche Inc. Hydro-1h-pyrrolo[1,2-a]pyrazine compounds for the treatment of autoimmune disease
EP4069693B1 (en) * 2019-12-03 2024-03-20 F. Hoffmann-La Roche AG Hydropyrido[1,2-alpha]pyrazine compounds for the treatment of autoimmune diseases
MX2023012110A (en) 2021-04-16 2023-10-24 Gilead Sciences Inc Thienopyrrole compounds.
TWI849499B (en) 2021-09-10 2024-07-21 美商基利科學股份有限公司 Thienopyrrole compounds
CN115073369A (en) * 2022-05-31 2022-09-20 汉瑞药业(荆门)有限公司 Preparation method of 5-bromoquinoline-8-formaldehyde

Family Cites Families (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE812911C (en) 1945-03-12 1951-09-06 Rhone Poulenc Sa Process for the preparation of new substituted derivatives of piperidine
CH578535A5 (en) * 1973-05-11 1976-08-13 Ciba Geigy Ag Quinoline-3-carboxylic acid derivs - with e.g. analgesic, antinociceptive, antiinflammatory and antiallergic props
US4933447A (en) 1987-09-24 1990-06-12 Ss Pharmaceutical Co., Ltd. Quinoline derivatives
FR2798656B1 (en) 1999-09-17 2004-12-17 Aventis Pharma Sa DERIVATIVES OF QUINOLYL PROPYL PIPERIDINE, THEIR PREPARATION AND THE COMPOSITIONS CONTAINING THEM
PL369674A1 (en) 2001-11-14 2005-05-02 Merck Patent Gmbh Pyrazole derivatives as psychopharmaceuticals
GB0206033D0 (en) * 2002-03-14 2002-04-24 Pfizer Ltd Compounds useful in therapy
WO2003105850A1 (en) * 2002-06-18 2003-12-24 Abbott Laboratories 2-aminoquinolines as melanin concentrating hormone receptor antagonists
WO2004016576A1 (en) 2002-08-12 2004-02-26 Takeda Pharmaceutical Company Limited Fused benzene derivative and use
CA2505873A1 (en) 2002-11-12 2004-05-27 Pfizer Products Inc. Quinoline derivatives
GB0227240D0 (en) * 2002-11-21 2002-12-31 Glaxo Group Ltd Compounds
US20050124625A1 (en) 2003-10-21 2005-06-09 Salvati Mark E. Piperazine derivatives and their use as modulators of nuclear hormone receptor function
JPWO2005087749A1 (en) * 2004-03-15 2007-08-09 協和醗酵工業株式会社 2-Aminoquinazoline derivatives
US20060211752A1 (en) 2004-03-16 2006-09-21 Kohn Leonard D Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression
US20070004679A1 (en) 2004-05-17 2007-01-04 Nathalie Schlienger Androgen receptor modulators and methods of treating disease using the same
CN101248069A (en) 2004-05-17 2008-08-20 阿卡蒂亚药品公司 Androgen receptor modulators and method of treating disease using the same
EP1772454A4 (en) 2004-07-23 2009-02-25 Mitsubishi Tanabe Pharma Corp Nitrogenous fused bicyclic compound
GB0510810D0 (en) * 2005-05-26 2005-06-29 Novartis Ag Organic compounds
GB0526042D0 (en) * 2005-12-21 2006-02-01 Syngenta Participations Ag Chemical compounds
US20090042857A1 (en) 2006-02-20 2009-02-12 Masuo Yamaoka Novel Pharmaceutical
EP1903038A1 (en) 2006-09-07 2008-03-26 Bayer Schering Pharma Aktiengesellschaft N-(1-hetaryl-piperidin-4-yl)-(het)arylamide as EP2 receptor modulators
US20100004452A1 (en) 2006-09-26 2010-01-07 Barbara Bertani 5-quinolinone derivatives as 5ht1a receptor modulators for treating sexual dysfunction, cognition impairment, psychotic disorders, anxiety, depression, etc.
CL2008001002A1 (en) 2007-04-11 2008-10-17 Actelion Pharmaceuticals Ltd COMPOUNDS DERIVED FROM OXAZOLIDINONA; PHARMACEUTICAL COMPOSITION THAT INCLUDES SUCH COMPOUNDS; AND ITS USE TO PREPARE A MEDICINAL PRODUCT TO TREAT A BACTERIAL INFECTION.
KR101608702B1 (en) * 2007-06-05 2016-04-04 사노피 Di(hetero)arylcyclohexane derivatives, their preparation, their use and pharmaceutical compositions comprising them
WO2009140200A1 (en) * 2008-05-12 2009-11-19 Amnestix, Inc. Compounds for improving learning and memory
US20110201599A1 (en) 2008-07-03 2011-08-18 Exelixis, Inc. CDK Modulators
KR20110058866A (en) 2008-09-02 2011-06-01 노파르티스 아게 Bicyclic kinase inhibitors
JP5697601B2 (en) 2008-12-01 2015-04-08 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ 2,5-Diamino-substituted pyrido [4,3-D] pyrimidines as autotaxin inhibitors against cancer
CA2752074A1 (en) 2009-02-11 2010-08-19 The Regents Of The University Of California Toll-like receptor modulators and treatment of diseases
WO2010097410A1 (en) 2009-02-24 2010-09-02 Respiratorius Ab Novel bronchodilating diazaheteroaryls
DK2453895T3 (en) 2009-07-16 2018-08-27 Mallinckrodt Llc (+) - MORPHINANES AS ANTAGONISTS OF TOLL-LIKE RECEPTOR 9 AND THERAPEUTIC APPLICATIONS THEREOF
US20120214803A1 (en) 2011-02-18 2012-08-23 Vifor (International) Ag Novel Sulfonaminoquinoline Hepcidin Antagonists
JP2013075834A (en) * 2011-09-29 2013-04-25 Kowa Co Pyrazolopyrimidine-7-amine derivative exhibiting tlr9-inhibiting activity
WO2013060881A1 (en) 2011-10-27 2013-05-02 Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg Pyridopyrimidines and their therapeutic use
WO2014086453A1 (en) 2012-12-07 2014-06-12 Merck Patent Gmbh Azaheterobicyclic compounds
UY35630A (en) 2013-06-26 2015-01-30 Abbvie Inc PRIMARY CARBOXAMIDS AS BTK INHIBITORS
CN105682661B (en) * 2013-08-23 2020-03-27 润新生物公司 Certain chemical entities, compositions, and methods
US9663486B2 (en) 2013-10-14 2017-05-30 Eisai R&D Management Co., Ltd. Selectively substituted quinoline compounds
ES2773303T3 (en) * 2013-10-14 2020-07-10 Eisai R&D Man Co Ltd Selectively substituted quinoline compounds
CN104557913B (en) 2013-10-28 2017-02-08 上海汇伦生命科技有限公司 Pyridopyrimidine compounds as well as preparation method and application thereof
WO2015088045A1 (en) 2013-12-13 2015-06-18 Takeda Pharmaceutical Company Limited Pyrrolo[3,2-c]pyridine derivatives as tlr inhibitors
US9695171B2 (en) 2013-12-17 2017-07-04 Pfizer Inc. 3,4-disubstituted-1 H-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazines as LRRK2 inhibitors
US9938282B2 (en) 2014-02-05 2018-04-10 Stereokem, Inc. Expedient synthesis of sitagliptin
CN104945377A (en) 2014-03-24 2015-09-30 南京明德新药研发股份有限公司 Quinoline derivatives used as SMO inhibitors
US9938292B2 (en) 2014-03-24 2018-04-10 Guangdong Zhongsheng Pharmaceutical Co., Ltd Quinoline derivatives as SMO inhibitors
MX2016013689A (en) 2014-04-22 2017-01-20 Hoffmann La Roche 4-amino-imidazoquinoline compounds.
GB201411236D0 (en) 2014-06-25 2014-08-06 Takeda Pharmaceutical Novel compounds
CA2965741C (en) 2014-11-03 2022-05-17 Iomet Pharma Ltd Pharmaceutical compound
UY36390A (en) * 2014-11-05 2016-06-01 Flexus Biosciences Inc MODULATING COMPOUNDS OF INDOLAMINE ENZYME 2,3-DIOXYGENASE (IDO), ITS SYNTHESIS METHODS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
BE1023340B1 (en) * 2014-11-13 2017-02-08 Glaxosmithkline Biologicals S.A. COMPOUNDS
WO2016087593A1 (en) * 2014-12-05 2016-06-09 Syngenta Participations Ag Novel fungicidal quinolinylamidines
MA41169A (en) 2014-12-17 2017-10-24 Acraf WIDE-SPECTRUM ANTIBACTERIAL COMPOUNDS
JP2018525345A (en) 2015-07-01 2018-09-06 ノースウェスタン ユニバーシティ Substituted quinazoline compounds and their use for modulation of glucocerebrosidase activity
WO2017031427A1 (en) 2015-08-19 2017-02-23 3-V Biosciences, Inc. COMPOUNDS AND METHODS FOR INHIBITING mTOR
MX2021006804A (en) 2015-12-17 2023-01-13 Merck Patent Gmbh Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders.
US20190119236A1 (en) * 2016-02-23 2019-04-25 Portola Pharmaceuticals, Inc. Compounds for binding proprotein convertase subtilisin/kexin type 9 (pcsk9)
WO2018031434A1 (en) 2016-08-08 2018-02-15 Merck Patent Gmbh Tlr7/8 antagonists and uses thereof
PL3558984T3 (en) * 2016-12-20 2024-01-15 Fmc Corporation Fungicidal oxadiazoles
US11050028B2 (en) * 2017-01-24 2021-06-29 Universal Display Corporation Organic electroluminescent materials and devices
JP7239554B2 (en) 2017-07-18 2023-03-14 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング TLR7/8 antagonists and their uses
WO2019125849A1 (en) 2017-12-19 2019-06-27 Merck Patent Gmbh Tlr7/8 antagonists and uses thereof
KR20210040085A (en) 2018-07-31 2021-04-12 메르크 파텐트 게엠베하 TLR7/8 antagonist and uses thereof

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