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NZ744194B2 - 5-ethyl-4-methyl-pyrazole-3-carboxamide derivative having activity as agonist of taar - Google Patents

5-ethyl-4-methyl-pyrazole-3-carboxamide derivative having activity as agonist of taar Download PDF

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Publication number
NZ744194B2
NZ744194B2 NZ744194A NZ74419417A NZ744194B2 NZ 744194 B2 NZ744194 B2 NZ 744194B2 NZ 744194 A NZ744194 A NZ 744194A NZ 74419417 A NZ74419417 A NZ 74419417A NZ 744194 B2 NZ744194 B2 NZ 744194B2
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NZ
New Zealand
Prior art keywords
compound
formula
disorders
acid addition
addition salt
Prior art date
Application number
NZ744194A
Other versions
NZ744194A (en
Inventor
Guido Galley
Marius Hoener
Roger Norcross
Philippe Pflieger
Original Assignee
F Hoffmann La Roche Ag
Filing date
Publication date
Application filed by F Hoffmann La Roche Ag filed Critical F Hoffmann La Roche Ag
Priority claimed from PCT/EP2017/055885 external-priority patent/WO2017157873A1/en
Publication of NZ744194A publication Critical patent/NZ744194A/en
Publication of NZ744194B2 publication Critical patent/NZ744194B2/en

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    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/282—Organic compounds, e.g. fats
    • A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
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    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
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    • 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
    • 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
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention relates to a compound of formula (I) and to a pharmaceutically suitable acid addition salt thereof with a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1, for the treatment of certain CNS diseases.

Claims (11)

Claims
1. A compound of a I: and a pharmaceutically le acid addition salt thereof.
2. The compound of formula I according to claim 1, which is 5-ethylmethyl-N-[4-[(2S) morpholinyl]phenyl]-1H-pyrazolecarboxamide.
3. The nd of a I according to claim 1, which is a pharmaceutically suitable 10 acid addition salt of 5-ethylmethyl-N-[4-[(2S) morpholinyl]phenyl]-1H-pyrazole carboxamide.
4. The compound of formula I according to claim 3, wherein the pharmaceutically suitable acid addition salt is a hydrochloride salt.
5. A process for the manufacture of the compound of formula I according to any one of claims 1 to 4, which process comprises a) cleaving off the N-protecting group (PG) from compounds of formula 20 to a compound of formula wherein PG is a N-protecting group, selected from –C(O)O-tert-butyl (BOC), and, if d, converting the compounds obtained into pharmaceutically acceptable acid addition salts.
6. A pharmaceutical ition comprising the compound of formula I ing to any one of claims 1 to 4 and pharmaceutically acceptable excipients.
7. The use of a compound of formula I according to any one of claims 1 to 4 for the 10 ation of a medicament for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, schizophrenia, Parkinson’s disease, Alzheimer’s e, epilepsy, migraine, hypertension, substance abuse, addiction, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and 15 assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and ian rhythm, and cardiovascular disorders.
8. The compound of formula I according to any one of claims 1 to 4, ntially as herein bed with reference to any example thereof.
9. The process according to claim 5, substantially as herein described with reference to any example thereof.
10. The pharmaceutical ition according to claim 6, substantially as herein 25 described with reference to any example thereof.
11. The use according to claim 7, substantially as herein described with reference to any example thereof.
NZ744194A 2017-03-14 5-ethyl-4-methyl-pyrazole-3-carboxamide derivative having activity as agonist of taar NZ744194B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16160790 2016-03-17
PCT/EP2017/055885 WO2017157873A1 (en) 2016-03-17 2017-03-14 5-ethyl-4-methyl-pyrazole-3-carboxamide derivative having activity as agonist of taar

Publications (2)

Publication Number Publication Date
NZ744194A NZ744194A (en) 2024-09-27
NZ744194B2 true NZ744194B2 (en) 2025-01-07

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