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WO2019005682A1 - Utilisation d'amphiphiles de benzothiazole pour traiter une lésion cérébrale traumatique - Google Patents

Utilisation d'amphiphiles de benzothiazole pour traiter une lésion cérébrale traumatique Download PDF

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Publication number
WO2019005682A1
WO2019005682A1 PCT/US2018/039322 US2018039322W WO2019005682A1 WO 2019005682 A1 WO2019005682 A1 WO 2019005682A1 US 2018039322 W US2018039322 W US 2018039322W WO 2019005682 A1 WO2019005682 A1 WO 2019005682A1
Authority
WO
WIPO (PCT)
Prior art keywords
substituted
unsubstituted
benzothiazole
tbi
traumatic brain
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/US2018/039322
Other languages
English (en)
Inventor
Vincent F. Simmon
Stella SARRAF
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.)
Spinogenix Inc
Original Assignee
Spinogenix Inc
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 Spinogenix Inc filed Critical Spinogenix Inc
Publication of WO2019005682A1 publication Critical patent/WO2019005682A1/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
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings

Definitions

  • FIG. 4 Sensorimotor recovery measured by the hindlimb footfault test for rats having TBI treated with BTA-EG4 ("BTA-EG4") compared to untreated rats having TBI ("DMSO”) at day 0 (preinjury), day 1, day 7, day 14, day 21 and day 35 after TBI.
  • BTA-EG4 BTA-EG4
  • FIG. 10 Novel object recognition (NOR) test for rats having TBI treated with BTA ⁇ EG4 ("BTA-EG4") compared to untreated rats having TBI (“DMSO”) at day 14 and day 35 after TBI.
  • BTA-EG4 BTA ⁇ EG4
  • the rings of a fused ring aryl or bridged ring aryl can be aryl rings.
  • An aryl can be monocyclic or polycyclic.
  • An aryl can have two, three, four, or five rings.
  • a heteroaryl can be a fused ring heteroaryl, wherein the fused rings are one or more heteroaryl rings and optionally one or more cycloalkyl, heterocycloalkyl, and/or aryl rings.
  • a heteroaryl can be a bridged ring heteroaryl, wherein the bridged rings are one or more heteroaryl rings and optionally one or more cycloalkyl, heterocycloalkyl, and/or aryl rings.
  • a point of attachment of a ring to the remainder of a molecule is not limited to a single atom (a floating substituent)
  • the attachment point may be any atom of the ring and in the case of fused rings, bridged rings, or spirocyclic rings, any atom of any of the fused rings, bridged rings, or spirocyclic rings while obeying the rules of chemical valency.
  • a ring, fused rings, bridged rings, or spirocyclic rings contain one or more ring heteroatoms and the ring, fused rings, bridged rings, or spirocyclic rings are shown with one or more floating substituents (including, but not limited to, points of attachment to the remainder of the molecule), the floating substituents may be bonded to the heteroatoms.
  • the ring heteroatoms are shown bound to one or more hydrogens (e.g. a ring nitrogen with two bonds to ring atoms and a third bond to a hydrogen) in the structure or formula with the floating substituent, when the heteroatom is bonded to the floating substituent, the substituent will be understood to replace the hydrogen, while obeying the rules of chemical valency.
  • n of formula (I) is an integer from 1 to 20.
  • n is an integer from 1 to 15, 1 to 14, 1 to 13, or 1 to 12.
  • n can be an integer from 3 to 12, 3 to 10, 3 to 8, 3 to 6, or 3 to 5.
  • n can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, or 20.
  • n is 3 to 5.
  • the present invention also provides compounds which are in a prodrug form.
  • Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention.
  • prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment.
  • prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.
  • the prodrug form may include a phosphate derivative or a sugar (e.g. ribose) derivative.
  • Dragee cores are provided with suitable coatings such as concentrated sugar solutions, which may also contain gum arable, talc, polyvinylpyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures.
  • Dyestuffs or pigments may be added to the tablets or dragee coatings for product identification or to characterize the quantity of active compound (i .e., dosage of the
  • the measured performance of one or more functional domains in a patient will improve by a percentage (%) compared to the performance of the one or more functional domains measured prior to treatment but after injury.
  • the performance of one or more functional domains can improve by at least 1% compared to the performance of the one or more functional domains measured prior to treatment but after injury, or by at least 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70 or 80% compared to the performance of the one or more functional domains measured prior to treatment but after injury.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des procédés de réduction des symptômes d'une lésion cérébrale traumatique chez des patients par l'administration, dans les 72 heures de survenue de la lésion, d'une quantité thérapeutiquement efficace d'un composé amphiphile de benzothiazole à un patient souffrant d'une lésion cérébrale traumatique.
PCT/US2018/039322 2017-06-26 2018-06-25 Utilisation d'amphiphiles de benzothiazole pour traiter une lésion cérébrale traumatique Ceased WO2019005682A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201762524758P 2017-06-26 2017-06-26
US62/524,758 2017-06-26
US201762574635P 2017-10-19 2017-10-19
US62/574,635 2017-10-19

Publications (1)

Publication Number Publication Date
WO2019005682A1 true WO2019005682A1 (fr) 2019-01-03

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2018/039322 Ceased WO2019005682A1 (fr) 2017-06-26 2018-06-25 Utilisation d'amphiphiles de benzothiazole pour traiter une lésion cérébrale traumatique

Country Status (1)

Country Link
WO (1) WO2019005682A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020160332A1 (fr) * 2019-01-31 2020-08-06 Spinogenix, Inc. Formes solides d'un promoteur de la spinogenèse
US11117878B2 (en) 2017-08-02 2021-09-14 Spinogenix, Inc. Benzothiazole and related compounds
EP4294391A4 (fr) * 2021-02-22 2024-12-18 Spinogenix, Inc. Méthodes de traitement d'une lésion ou d'un endommagement de la moelle épinière
US12486287B2 (en) 2020-01-30 2025-12-02 Spinogenix, Inc. Solid forms of a promoter of spinogenesis

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110105621A1 (en) * 2006-08-23 2011-05-05 The University Of Montana Method of reducing brain cell damage, inflammation or death
WO2014134287A1 (fr) * 2013-02-27 2014-09-04 The Regents Of The University Of California Amélioration de la fonction cognitive
US20160220206A1 (en) * 2015-02-04 2016-08-04 Oren E. Petel Diagnostic for in situ Deformation and Strain Measurements Applicable to Traumatic Internal Injury Investigation and Prevention

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110105621A1 (en) * 2006-08-23 2011-05-05 The University Of Montana Method of reducing brain cell damage, inflammation or death
WO2014134287A1 (fr) * 2013-02-27 2014-09-04 The Regents Of The University Of California Amélioration de la fonction cognitive
US20160220206A1 (en) * 2015-02-04 2016-08-04 Oren E. Petel Diagnostic for in situ Deformation and Strain Measurements Applicable to Traumatic Internal Injury Investigation and Prevention

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CIFELLI ET AL.: "Benzothiazole Amphiphiles Ameliorate Amyloid beta-Related Cell Toxicity and Oxidative Stress", ACS CHEMICAL NEUROSCIENCE, vol. 7, no. 6, 2016, pages 682 - 688, XP055397284 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11117878B2 (en) 2017-08-02 2021-09-14 Spinogenix, Inc. Benzothiazole and related compounds
US12391659B2 (en) 2017-08-02 2025-08-19 Spinogenix, Inc. Benzothiazole and related compounds
WO2020160332A1 (fr) * 2019-01-31 2020-08-06 Spinogenix, Inc. Formes solides d'un promoteur de la spinogenèse
US12486287B2 (en) 2020-01-30 2025-12-02 Spinogenix, Inc. Solid forms of a promoter of spinogenesis
EP4294391A4 (fr) * 2021-02-22 2024-12-18 Spinogenix, Inc. Méthodes de traitement d'une lésion ou d'un endommagement de la moelle épinière

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