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WO2017019817A1 - Méthodes et compositions pour une thérapeutique ciblée - Google Patents

Méthodes et compositions pour une thérapeutique ciblée Download PDF

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Publication number
WO2017019817A1
WO2017019817A1 PCT/US2016/044353 US2016044353W WO2017019817A1 WO 2017019817 A1 WO2017019817 A1 WO 2017019817A1 US 2016044353 W US2016044353 W US 2016044353W WO 2017019817 A1 WO2017019817 A1 WO 2017019817A1
Authority
WO
WIPO (PCT)
Prior art keywords
variations
rbi
rdi
independently
formulae
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2016/044353
Other languages
English (en)
Inventor
Roopa Rai
Son Minh Pham
Barry Patrick Hart
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medivation Technologies LLC
Original Assignee
Medivation Technologies LLC
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 Medivation Technologies LLC filed Critical Medivation Technologies LLC
Publication of WO2017019817A1 publication Critical patent/WO2017019817A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/46—Phenazines

Definitions

  • Heterocyclyl refers to a saturated or an unsaturated non-aromatic group having a single ring or multiple condensed rings, and having from 1 to 10 annular carbon atoms (e.g. , 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2- 10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-
  • R b3 is H.
  • R a i and R b i are " 3 ⁇ 4 ⁇
  • R a2 and Rb2 are ' 3 ⁇ 4 ⁇
  • R a i and Rbi are ' 3 ⁇ 4
  • R a2 and Rb 2 are ' 3 ⁇ 4 ⁇ and each of R a3 and
  • Rbi are ' 3 ⁇ 4
  • R a2 and Rb 2 are ' 3 ⁇ 4
  • R a3 and Rb 3 are H
  • R a i and R b i are , R a2 and R b2 are R a3 and R b3 are
  • R a 4 and Rb4 are '3 ⁇ 4 ⁇ ⁇
  • R a i and R b i are '3 ⁇ 4 ⁇ ⁇ 5
  • R a2 and R b2 are '3 ⁇ 4 ⁇ R a3
  • R a i and R b i; R a2 and R b2 ; R a3 and R b3 ; R a 4 and R b4 ; R a s and R b s ; R a 6 and Rb6i and R a7 and R b7 are as described above, and each of R a s is H, and R b8 is CH 3 .
  • R a i and R b i are both CH 3 . In some variations, R a i and R b i are ' 3 ⁇ 4 ⁇ . In
  • each of Rai.i and Rbi.i is H and R a i. 2 and Rbi. 2 are ' 3 ⁇ 4 .
  • R a i. 2 and Rbi. 2 are ' 3 ⁇ 4 .
  • R a i.i and R b i.i are '3 ⁇ 4 ⁇
  • R a i. 2 and R b i. 2 are '3 ⁇ 4 ⁇ ⁇ * ⁇
  • R a i 1 and Rbi 1 are ' 3 ⁇ 4 ⁇
  • R a i 2 and Rbi 2 are ' 3 ⁇ 4 ⁇
  • each of R a i 3 and R b i 3 is H.
  • R a i 1 and R b i 1 are ' 3 ⁇ 4 ⁇ " 5 al 2 and R b i 2 are ' 3 ⁇ 4
  • each of R a i 3 and R b i 3 is CH 3 .
  • R a i 1 and R b i 1 are ' 3 ⁇ 4
  • R a i. 2 and R b i. 2 are ⁇ ⁇
  • R a i. 3 is H
  • R b i. 3 is CH 3 .
  • R b i.2 are '3 ⁇ 4 ⁇ ⁇
  • each of R a i.3 and R b i.3 is CH 3 .
  • R a i.i and R b i.i are '3 ⁇ 4 ⁇ ⁇ ,
  • Rbi. 3 are CH 3
  • R a i.4 and Rbi.4 are ' 3 ⁇ 4 ⁇ ⁇ .
  • R a i.i and Rbi.i are H
  • R a i. 2 and Rbi.2 are CH 3
  • R a i. 3 and Rbi.3 are ' 3 ⁇ 4 ⁇
  • R a i.4 and Rbi.4 are ' 3 ⁇ 4 ⁇ ⁇
  • R b i.i are ' ⁇ 3 ⁇ 4 3 ⁇ 4 ⁇
  • R a i. 2 and R b i. 2 are 3 ⁇ 4 ' 3 ⁇ 4 3 ⁇ 4 ⁇
  • R a i. 3 and R b i. 3 are H
  • R al .4 and R b i.4 In some variations, R a i.i and R b i.i are ' 3 ⁇ 4 R a i. 2 and R b i. 2 are " ⁇ - , R a i. 3 and R b i. 3 are CH 3 , and R a i. 4 and R b i. 4 are ' 3 ⁇ 4 ⁇ ⁇ . In some variations, R ai .i and
  • R a i.i and R b i.i are H
  • R a i. 2 and R b i. 2 are H
  • R a i. 3 and Rbi. 3 and R a i.4 and Rbi.4 together are ' « ⁇ ⁇ ⁇ .
  • R a i.i and Rbi.4 together are ' « ⁇ ⁇ ⁇ .
  • Rbi.2 are CH 3
  • R a i. 3 and Rbi. 3 and R a i.4 and Rbi.4 together are ⁇ ⁇ .
  • R a i.i and are ' 3 ⁇ 4
  • R a i. 2 and R b i. 2 are and R a i. 3 and
  • each of R a2 1 and R b2 1 is H and R a2 2 and R b2 2 are " 3 ⁇ 4 ⁇ ⁇ In some variations, each of
  • R a2 .4 and R b2 .4 are ' 3 ⁇ 4 ⁇ ⁇ .
  • R a2 .i and R b2 are ' 3 ⁇ 4 ⁇
  • R a2 . 2 and R b2 are O 0
  • R a2 .i and R b2 are A '3 ⁇ 4 ⁇ R a2 . 2 and R b2 are A '3 ⁇ 4 ⁇ R a2 . 3 and R b2 . 3 are H, and R a2 .4 and
  • R a2 .i and Rb 2 are ⁇ "
  • R a2 . 2 and Rb 2 are ⁇ x
  • R a2 .3 and Rb 2 .3 and R a2 .4 and Rb 2 .4 together
  • h is 0.
  • a first instance of h is 0.
  • a first instance of h is 2.
  • a first instance of 3 ⁇ 4 is 3.
  • a first instance of 3 ⁇ 4 is 4.
  • a second instance of h is 0.
  • a second instance of h is 1.
  • a second instance of h is 2.
  • a second instance of 3 ⁇ 4 is 3.
  • li is 1. In some variations in which li is 1, a first instance of I 2 is 0. In some variations in which li is 1, a first instance of I 2 is 2. In some variations in which li is 1, a first instance of 3 ⁇ 4 is 3. In some variations in which li is 1, a first instance of h is 4. In some of the variations described in this paragraph, a second instance of I 2 is 0. In some of the variations described in this paragraph, a second instance of I 2 is 1. In some of the variations described in this paragraph, a second instance of I 2 is 2. In some of the variations described in this paragraph, a second instance of h is 3.
  • each of R C 2.is 3 ⁇ 42.is R C 2.2S and Rd2.2s is H and R C 2.3' and Rd2.3' are O
  • Rd 2 are CH 3 '
  • R c2 .3' and Rd 2 .3' are CH 3 '
  • R c2 .4' and Rd 2 .4' are '3 ⁇ 4 ⁇ .
  • R c2 .4' and R d2 .4- are '3 ⁇ 4 ⁇ ⁇ ⁇ 7 0
  • Rc2.4- and Rd2.4' together are 'T 3 ⁇ 4 - .
  • R C 2.r and R d 2 are H
  • R C 2.2' and R d 2 are A '3 ⁇ 4 ⁇
  • R C 2. 3 ' and Rd2.3' are H
  • R d 2 is CH 3
  • R c2 . 2' and R d 2 are A '3 ⁇ 4 ⁇ and R c2 . 3' and R d 2.3' and R c2 . 4 - and R d 2.4' together are o o
  • R a i.i is H
  • Rbi.i is CH 3
  • R a i. 2 and Rbi. 2 are '3 ⁇ 4 ⁇ ⁇ .
  • R a i.i is H
  • Rbi.i is CH 3
  • R a i. 2 and Rbi. 2 are '3 ⁇ 4 ⁇ ⁇ .
  • each of Rai.i , Rbi.i, Rai.2, and Rbi.2 is H and each of R a i. 3 and Rbi. 3 is CH 3 .
  • each of Rai.i, Rbi.i, Rai.2, and Rbi.2 is CH 3 and each of R a i. 3 and Rbi. 3 is H.
  • R a i.i is H and each of R a i. 2 , R a i.3, R b i.i, 3 ⁇ 4L2, and Rbi. 3 is CH 3 .
  • each of R a i.i, Rbi.i, ai.2, and Rbi.2, is H and R a i. 3 and Rbi. 3 are ' 3 ⁇ 4 ⁇
  • each of R a i.i and R a i. 2 is H and each of R b i.i and R b i.2 is CH 3 , and

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des compostions et méthodes d'administration et de localisation de cellules réparatrices sur des cibles thérapeutiques.
PCT/US2016/044353 2015-07-29 2016-07-28 Méthodes et compositions pour une thérapeutique ciblée Ceased WO2017019817A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562198616P 2015-07-29 2015-07-29
US62/198,616 2015-07-29

Publications (1)

Publication Number Publication Date
WO2017019817A1 true WO2017019817A1 (fr) 2017-02-02

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10875848B2 (en) 2018-10-10 2020-12-29 Forma Therapeutics, Inc. Inhibiting fatty acid synthase (FASN)
US10973817B2 (en) 2014-02-10 2021-04-13 Sentinel Oncology Limited Pharmaceutical compounds
US11247987B2 (en) 2017-10-06 2022-02-15 Forma Therapeutics, Inc. Inhibiting ubiquitin specific peptidase 30
US11535618B2 (en) 2018-10-05 2022-12-27 Forma Therapeutics, Inc. Fused pyrrolines which act as ubiquitin-specific protease 30 (USP30) inhibitors
US11697666B2 (en) 2021-04-16 2023-07-11 Gilead Sciences, Inc. Methods of preparing carbanucleosides using amides
US11767337B2 (en) 2020-02-18 2023-09-26 Gilead Sciences, Inc. Antiviral compounds
US12030903B2 (en) 2020-02-18 2024-07-09 Gilead Sciences, Inc. Antiviral compounds
US12049466B2 (en) 2018-05-17 2024-07-30 Forma Therapeutics, Inc. Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors
US12054507B2 (en) 2020-02-18 2024-08-06 Gilead Sciences, Inc. Antiviral compounds
US12116380B2 (en) 2021-08-18 2024-10-15 Gilead Sciences, Inc. Phospholipid compounds and methods of making and using the same

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1433472A1 (fr) * 2002-12-23 2004-06-30 L'oreal Composition tinctoriale pour les fibres kératiniques humaines contenant un colorant direct tricationique
EP1433474A1 (fr) * 2002-12-23 2004-06-30 L'oreal Composition tinctoriale contenant un colorant direct polycationique dissymétrique particulier, procédé de teinture, utilisation et dispositifs à plusieurs compartiments
EP1433471A1 (fr) * 2002-12-23 2004-06-30 L'oreal Composition tinctoriale contenant un colorant direct polycationique particuler, procédé de teinture, utilisation et dispositifs à plusieurs compartiments
WO2006099605A2 (fr) * 2005-03-17 2006-09-21 Biotium, Inc. Colorants d'acides nucleiques dimeriques et trimeriques et systemes et procedes associes
WO2015116707A1 (fr) * 2014-01-28 2015-08-06 Medivation Technologies, Inc. Agents thérapeutiques ciblés

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1433472A1 (fr) * 2002-12-23 2004-06-30 L'oreal Composition tinctoriale pour les fibres kératiniques humaines contenant un colorant direct tricationique
EP1433474A1 (fr) * 2002-12-23 2004-06-30 L'oreal Composition tinctoriale contenant un colorant direct polycationique dissymétrique particulier, procédé de teinture, utilisation et dispositifs à plusieurs compartiments
EP1433471A1 (fr) * 2002-12-23 2004-06-30 L'oreal Composition tinctoriale contenant un colorant direct polycationique particuler, procédé de teinture, utilisation et dispositifs à plusieurs compartiments
WO2006099605A2 (fr) * 2005-03-17 2006-09-21 Biotium, Inc. Colorants d'acides nucleiques dimeriques et trimeriques et systemes et procedes associes
WO2015116707A1 (fr) * 2014-01-28 2015-08-06 Medivation Technologies, Inc. Agents thérapeutiques ciblés

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
R. JAMES CHRISTIE ET AL: "Optical Properties and Application of a Reactive and Bioreducible Thiol-Containing Tetramethylrhodamine Dimer", BIOCONJUGATE CHEMISTRY, vol. 20, no. 3, 18 March 2009 (2009-03-18), pages 476 - 480, XP055184658, ISSN: 1043-1802, DOI: 10.1021/bc800367e *
WILSON BETH ET AL: "Synthesis and DNA interactions of a bis-phenothiazinium photosensitizer.", ORGANIC & BIOMOLECULAR CHEMISTRY 7 NOV 2008, vol. 6, no. 21, 7 November 2008 (2008-11-07), pages 4026 - 4035, XP002763250, ISSN: 1477-0539 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10973817B2 (en) 2014-02-10 2021-04-13 Sentinel Oncology Limited Pharmaceutical compounds
US11786524B2 (en) 2014-02-10 2023-10-17 Sentinel Oncology Limited Pharmaceutical compounds
US11247987B2 (en) 2017-10-06 2022-02-15 Forma Therapeutics, Inc. Inhibiting ubiquitin specific peptidase 30
US12049466B2 (en) 2018-05-17 2024-07-30 Forma Therapeutics, Inc. Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors
US11814386B2 (en) 2018-10-05 2023-11-14 Forma Therapeutics, Inc. Fused pyrrolines which act as ubiquitin-specific protease 30 (USP30) inhibitors
US11535618B2 (en) 2018-10-05 2022-12-27 Forma Therapeutics, Inc. Fused pyrrolines which act as ubiquitin-specific protease 30 (USP30) inhibitors
US11299484B2 (en) 2018-10-10 2022-04-12 Forma Therapeutics, Inc. Inhibiting fatty acid synthase (FASN)
US10875848B2 (en) 2018-10-10 2020-12-29 Forma Therapeutics, Inc. Inhibiting fatty acid synthase (FASN)
US11767337B2 (en) 2020-02-18 2023-09-26 Gilead Sciences, Inc. Antiviral compounds
US12030903B2 (en) 2020-02-18 2024-07-09 Gilead Sciences, Inc. Antiviral compounds
US12054507B2 (en) 2020-02-18 2024-08-06 Gilead Sciences, Inc. Antiviral compounds
US12264173B2 (en) 2020-02-18 2025-04-01 Gilead Sciences, Inc. Antiviral compounds
US11697666B2 (en) 2021-04-16 2023-07-11 Gilead Sciences, Inc. Methods of preparing carbanucleosides using amides
US12116380B2 (en) 2021-08-18 2024-10-15 Gilead Sciences, Inc. Phospholipid compounds and methods of making and using the same

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