Classifications

• • 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
  • 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
  • C07D405/14—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 three or more hetero rings
• • 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
  • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
  • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
  • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

• Trk's are the high affinity receptor tyrosine kinases activated by a group of soluble growth factors called neurotrophins (NT).
• the Trk receptor family has three members-TrkA, TrkB and TrkC.
• the neurotrophins are (i) nerve growth factor (NGF) which activates TrkA, (ii) brain-derived neurotrophic factor (BDNF) and NT-4/5 which activate TrkB and (iii) NT3 which activates TrkC.
• Trk's are widely expressed in neuronal tissue and are implicated in the maintenance, signaling and survival of neuronal cells (Patapoutian, A. et al., Current Opinion in Neurobiology, 2001 , 11 , 272-280).
• NTRK1 encodes the TrkA receptor tyrosine kinase. TrkA activates the PI3K/AKT, PKC and ERK1/2 pathways which promote cell growth and survival.
• a crystalline form of N-[5-(3,5-difluoro-benzyl)-1 H-indazol-3-yl]-4-(4- methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide wherein said crystalline form is characterized by an x-ray powder diffraction pattern comprising peaks at a 2-theta value of about 15.6 and 17.9 degrees.
• such a crystalline form wherein said crystalline form is unsolvated.
• a crystalline form of N-[5-(3,5-difluoro-benzyl)-1 H-indazol-3-yl]-4-(4- methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide wherein said crystalline form is characterized by an x-ray powder diffraction pattern comprising peaks at a 2-theta value of about 15.6, 17.9 and 39.0 ⁇ 0.5 degrees.
• such a crystalline form wherein said crystalline form is unsolvated.
• a pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of N-[5-(3,5-difluoro-benzyl)-1 H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro- pyran-4-ylamino)-benzamide, wherein said crystalline form is characterized by exhibiting a peak in a differential scanning calorimetry scan of from about 200°C to about 205°C, and an x-ray powder diffraction pattern comprising a peak at a 2-theta value of about 15.6 ⁇ 0.5 degrees.
• a pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of N-[5-(3,5-difluoro-benzyl)-1 H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro- pyran-4-ylamino)-benzamide, wherein said crystalline form is characterized by exhibiting a peak in a differential scanning calorimetry scan of from about 200°C to about 205°C, and an x-ray powder diffraction pattern comprising a peak at a 2-theta value of about 15.6 ⁇ 0.2 degrees.
• Crystalline Form 4 as defined above may be administered by any administration route, for instance by oral, parenteral, topical, rectal and nasal route.
• the liquid dispersions for oral administration may be, e.g., syrups, emulsions and suspensions.
• the syrups may contain, as carrier, saccharose or saccharose with glycerine and/or mannitol and sorbitol.
• the suppositories may contain, together with the active compound, a pharmaceutically acceptable carrier, e.g., cocoa butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin.
• a pharmaceutically acceptable carrier e.g., cocoa butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin.
• the therapeutically effective dose of the crystalline Form 4 of compound of formula (I), as defined above, or a pharmaceutically acceptyable salt may vary according to the disease, severity of the disorder and the conditions of the patient to be treated. Therefore the physician, as always, must set the optimal dose for each patient.
• the effective dosage range may be from about 10 mg to about 1 g per dose (calculated as a free base), from 1 to 3 times daily.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Medicinal Chemistry (AREA)
• Public Health (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Priority Applications (15)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=58709993

Family Applications (1)

Country Status (12)

Cited By (4)

Families Citing this family (5)

Citations (3)

Family Cites Families (1)

• 2017
  • 2017-05-18 CN CN201780031576.6A patent/CN109153669B/zh active Active
  • 2017-05-18 US US16/301,826 patent/US10738037B2/en active Active
  • 2017-05-18 EP EP17724052.0A patent/EP3464276B1/en active Active
  • 2017-05-18 EP EP21188238.6A patent/EP3967689A1/en not_active Withdrawn
  • 2017-05-18 WO PCT/EP2017/061919 patent/WO2017202674A1/en not_active Ceased
  • 2017-05-18 MX MX2018014298A patent/MX379558B/es unknown
  • 2017-05-18 PL PL17724052T patent/PL3464276T3/pl unknown
  • 2017-05-18 KR KR1020187037182A patent/KR102441736B1/ko active Active
  • 2017-05-18 CA CA3024208A patent/CA3024208C/en active Active
  • 2017-05-18 JP JP2018561474A patent/JP7094228B2/ja active Active
  • 2017-05-18 ES ES17724052T patent/ES2899953T3/es active Active
  • 2017-05-18 AU AU2017271458A patent/AU2017271458B2/en active Active
• 2018
  • 2018-11-14 IL IL263004A patent/IL263004B/en unknown
• 2020
  • 2020-06-26 US US16/912,965 patent/US11091469B2/en active Active
  • 2020-11-06 JP JP2020185594A patent/JP7154271B2/ja active Active

Patent Citations (3)

Non-Patent Citations (23)

Also Published As

Similar Documents

Legal Events