CN115867532A - Apol1的抑制剂及其用途 - Google Patents

Apol1的抑制剂及其用途 Download PDF

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Publication number
CN115867532A
CN115867532A CN202180049447.6A CN202180049447A CN115867532A CN 115867532 A CN115867532 A CN 115867532A CN 202180049447 A CN202180049447 A CN 202180049447A CN 115867532 A CN115867532 A CN 115867532A
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Chinese (zh)
Inventor
J·曹
J·H·科姆
L·A·达金
F·德尼斯
W·A·多尔施
A·富尔捷
M·哈梅尔
E·B·克吕格尔
B·勒福德
F·马尔泰斯
S·S·南塔库马
O·尼科拉斯
C·E·赛伊
T·J·森特
T·王
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Vertex Pharmaceuticals Inc
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Vertex Pharmaceuticals Inc
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Publication of CN115867532A publication Critical patent/CN115867532A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C07D209/16—Tryptamines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN202180049447.6A 2020-06-12 2021-06-11 Apol1的抑制剂及其用途 Pending CN115867532A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063038276P 2020-06-12 2020-06-12
US63/038276 2020-06-12
PCT/US2021/036944 WO2021252849A1 (en) 2020-06-12 2021-06-11 Inhibitors of apol1 and use of the same

Publications (1)

Publication Number Publication Date
CN115867532A true CN115867532A (zh) 2023-03-28

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CN202180049447.6A Pending CN115867532A (zh) 2020-06-12 2021-06-11 Apol1的抑制剂及其用途

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US (1) US20230014907A1 (https=)
EP (1) EP4165023A1 (https=)
JP (1) JP2023529216A (https=)
CN (1) CN115867532A (https=)
AU (1) AU2021286666A1 (https=)
CA (1) CA3185144A1 (https=)
WO (1) WO2021252849A1 (https=)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116789603A (zh) * 2023-06-06 2023-09-22 南昌大学 一种新型多菌灵半抗原、全抗原、抗体及其制备方法及应用
WO2026012338A1 (zh) * 2024-07-09 2026-01-15 上海旭成医药科技有限公司 一种APOLs抑制剂

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11618746B2 (en) 2018-12-17 2023-04-04 Vertex Pharmaceuticals Incorporated Inhibitors of APOL1 and methods of using same
WO2021154997A1 (en) 2020-01-29 2021-08-05 Vertex Pharmaceuticals Incorporated Inhibitors of apol1 and methods of using same
IL296035A (en) 2020-03-06 2022-10-01 Vertex Pharma Methods of treating apol-1 dependent focal segmental glomerulosclerosis
CA3185604A1 (en) 2020-06-12 2021-12-16 Vertex Pharmaceuticals Incorporated Inhibitors of apol1 and use of the same
CN115867543A (zh) 2020-06-12 2023-03-28 弗特克斯药品有限公司 Apol1抑制剂的固体形式及其使用方法
CN116547287B (zh) 2020-08-26 2025-09-26 弗特克斯药品有限公司 Apol1的抑制剂及其使用方法
US12612379B2 (en) 2021-11-30 2026-04-28 Vertex Pharmaceuticals Incorporated Inhibitors of APOL1 and methods of using same
WO2023115167A1 (en) * 2021-12-24 2023-06-29 Psylo Pty Ltd Compounds
MX2024008868A (es) 2022-01-18 2024-09-23 Maze Therapeutics Inc Inhibidores de la apolipoproteína l1 (apol1) y métodos de uso.
CN119212986A (zh) * 2022-02-08 2024-12-27 弗特克斯药品有限公司 作为apol1的抑制剂的螺哌啶衍生物及其使用方法
EP4476228A1 (en) * 2022-02-08 2024-12-18 Vertex Pharmaceuticals Incorporated 4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] derivatives as inhibitors of apol1 and methods of using same
AU2023219516A1 (en) * 2022-02-08 2024-08-22 Vertex Pharmaceuticals Incorporated 2-methyl-4-phenylpiperidin-4-ol derivatives as inhibitors of apol1 and methods of using same
WO2024220852A2 (en) * 2023-04-20 2024-10-24 University Of Florida Research Foundation, Incorporated Tead core inhibitors for cancer therapeutics
WO2024242846A1 (en) * 2023-05-03 2024-11-28 Omniab, Inc. Heteroarylindole inhibitors of apol-1
WO2025042797A1 (en) * 2023-08-18 2025-02-27 Shattuck Labs, Inc. Trim7 inhibitors and uses thereof
GB202401326D0 (en) * 2024-02-01 2024-03-20 Podium Bio Ltd Novel compounds
WO2025231011A1 (en) * 2024-05-01 2025-11-06 Omniab, Inc. Heteroarylindole inhibitors of apol-1

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WO2001038305A2 (fr) * 1999-11-25 2001-05-31 Fournier Industrie Et Sante Nouveaux antagonistes des recepteurs de l'il-8
WO2002092568A1 (fr) * 2001-05-17 2002-11-21 Laboratoires Fournier Sa Derives de 5-cyano-1h-indole antagonistes des recepteurs de l'interleukine-8
JP2008195642A (ja) * 2007-02-13 2008-08-28 Asahi Kasei Corp インドール誘導体

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US5206382A (en) * 1991-06-27 1993-04-27 Fidia Georgetown Institute For The Neurosciences Indole derivatives, pharmaceutical compositions and methods of treating neurological and psychiatric disorders
EP0924209B1 (en) * 1997-12-19 2003-05-02 Eli Lilly And Company Hypoglycemic imidazoline compounds
GB9905010D0 (en) * 1999-03-04 1999-04-28 Merck Sharp & Dohme Therapeutic agents
GB0003397D0 (en) * 2000-02-14 2000-04-05 Merck Sharp & Dohme Therapeutic agents
AU2002211828A1 (en) * 2000-10-02 2002-04-15 Merck & Co., Inc. Inhibitors of prenyl-protein transferase
FR2824827B1 (fr) * 2001-05-17 2004-02-13 Fournier Lab Sa Nouveaux derives de 5-phenyl-1h-indole antagoniste des recepteurs de l'interleukine-8
WO2007061763A2 (en) * 2005-11-22 2007-05-31 Merck & Co., Inc. Indole orexin receptor antagonists
DK2178870T3 (en) * 2007-08-17 2018-10-22 Lg Chemical Ltd INDOLE AND INDAZOLIC COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSE
EP3186225A4 (en) * 2014-08-27 2018-02-28 The Governing Council of the University of Toronto Cannabinoid type 1 receptor modulators
US11618746B2 (en) * 2018-12-17 2023-04-04 Vertex Pharmaceuticals Incorporated Inhibitors of APOL1 and methods of using same
WO2021154997A1 (en) * 2020-01-29 2021-08-05 Vertex Pharmaceuticals Incorporated Inhibitors of apol1 and methods of using same

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
WO2001038305A2 (fr) * 1999-11-25 2001-05-31 Fournier Industrie Et Sante Nouveaux antagonistes des recepteurs de l'il-8
WO2002092568A1 (fr) * 2001-05-17 2002-11-21 Laboratoires Fournier Sa Derives de 5-cyano-1h-indole antagonistes des recepteurs de l'interleukine-8
JP2008195642A (ja) * 2007-02-13 2008-08-28 Asahi Kasei Corp インドール誘導体

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A. P. KOZIKOWSKI等: "Chemistry, Binding Affinities, and Behavioral Properties of a New Class of"Antineophobic" Mitochondrial DBI Receptor Complex (mDRC) Ligands", J. MED. CHEM., vol. 36, no. 20, 1 January 1993 (1993-01-01), pages 2909 *
A.N.GRINEV等: "Synthesis of aldehydes and nitriles in the 5-hydroxyindole series", CHEMISTRY OF HETEROCYCLIC COMPOUNDS, vol. 11, 31 December 1975 (1975-12-31), pages 1087 - 1090, XP002803923, DOI: Synthesis of aldehydes and nitriles in the 5-hydroxyindole series *
MICHAEL P. WINTERS等: "Carboxylic acid bioisosteres acylsulfonamides, acylsulfamides, and sulfonylureas as novel antagonists of the CXCR2 receptor", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 18, no. 6, 15 March 2008 (2008-03-15), pages 1926 - 1927 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116789603A (zh) * 2023-06-06 2023-09-22 南昌大学 一种新型多菌灵半抗原、全抗原、抗体及其制备方法及应用
WO2026012338A1 (zh) * 2024-07-09 2026-01-15 上海旭成医药科技有限公司 一种APOLs抑制剂

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CA3185144A1 (en) 2021-12-16
WO2021252849A1 (en) 2021-12-16
EP4165023A1 (en) 2023-04-19
JP2023529216A (ja) 2023-07-07
AU2021286666A1 (en) 2023-01-19
US20230014907A1 (en) 2023-01-19

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Application publication date: 20230328