CA2427560A1 - Alkynyl amides and their therapeutic applications - Google Patents

Alkynyl amides and their therapeutic applications Download PDF

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Publication number
CA2427560A1
CA2427560A1 CA002427560A CA2427560A CA2427560A1 CA 2427560 A1 CA2427560 A1 CA 2427560A1 CA 002427560 A CA002427560 A CA 002427560A CA 2427560 A CA2427560 A CA 2427560A CA 2427560 A1 CA2427560 A1 CA 2427560A1
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propyl
hexynamide
compound
oxoethyl
amino
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CA002427560A
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French (fr)
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CA2427560C (en
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Youssef L. Bennani
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Abbott Laboratories
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Individual
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/12—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/06—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
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/28—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
    • 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
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/09—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic unsaturated carbon skeleton
    • 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
    • C07B2200/07—Optical isomers

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Hospice & Palliative Care (AREA)
  • Anesthesiology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Compounds of formula (I), are novel and useful for treating seizure, migraine and psychiatric disorders.

Claims (30)

1. A compound of formula (I) wherein R1 is selected from the group consisting of alkyl and haloalkyl;
R2 is selected from the group consisting of hydrogen, alkyl and fluorine;
R3 is selected from the group consisting of hydrogen, alkyl and (NR A R
B)carbonylalkyl wherein R A and R B are each independently selected from the group consisting of hydrogen and alkyl;
R4 is selected from the group consisting of hydrogen and alkyl; and R5 is selected from the group consisting of hydrogen and alkyl.
2. A compound according to claim 1 wherein R1 is alkyl wherein said alkyl is propyl; and R5 is alkyl wherein said alkyl is methyl.
3. A compound according to claim 2 wherein R3 is hydrogen.
4. A compound according to claim 3 that is (2R)-2-propyl-4-hexynamide.
5. A compound according to claim 2 wherein R3 is (NR A R B)carbonylalkyl.
6. A compound according to claim 5 selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;

(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
7. A compound according to claim 2 wherein R3 is (NR AR B)carbonylalkyl; and R2 is fluorine.
8. A compound according to claim 2 wherein R3 is (NR AR B)carbonylalkyl; and R2 is alkyl.
9. A method of treating seizures in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (I).
10. A method of treating epilepsy in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (I).
11. A method of treating migraine in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (I).
12. A method of treating psychiatric disorders selected from the group consisting of Mood Disorders, Anxiety Disorders, Attention-Deficit and Disruptive Behavior Disorders, Behavioral Disturbances associated with dementia, Substance Abuse-related Disorders, Schizophrenia, Impulse Control Disorders, Personality Disorders and Behavioral Disturbances associated with autism in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (I).
13. A method of treating neuropathic pain in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (I).
14. A method of treating restlessness syndrome in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (I).
15. A method of providing neuroprotection to a mammal suffering from a cerebral insult, comprising administering to said mammal a therapeutically effective amount of a compound of formula (I).
16. The method of claim 9, wherein the compound is (2R)-2-propyl-4-hexynamide.
17. The method of claim 10, wherein the compound is (2R)-2-propyl-4-hexynamide.
18. The method of claim 11, wherein the compound is (2R)-2-propyl-4-hexynamide.
19. The method of claim 12, wherein the compound is (2R)-2-propyl-4-hexynamide.
20. The method of claim 13, wherein the compound is (2R)-2-propyl-4-hexynamide.
21. The method of claim 14, wherein the compound is (2R)-2-propyl-4-hexynamide.
22. The method of claim 15, wherein the compound is (2R)-2-propyl-4-hexynamide.
23. The method of claim 9, wherein the compound is selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;

(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
24. The method of claim 10, wherein the compound is selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
25. The method of claim 11, wherein the compound is selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
26. The method of claim 12, wherein the compound is selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
27. The method of claim 13, Wherein the compound is selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
28. The method of claim 14, wherein the compound is selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
29. The method of claim 15, wherein said compound is selected from the group consisting of (2R)-N-(2-amino-2-oxoethyl)-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-1-(aminocarbonyl)-3-methylbutyl]-2-propyl-4-hexynamide;
(2R)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide; and (2R)-N-[(1R)-2-amino-1-methyl-2-oxoethyl]-2-propyl-4-hexynamide.
30. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.
CA2427560A 2000-11-01 2001-10-31 Alkynyl amides and their therapeutic applications Expired - Fee Related CA2427560C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US70377100A 2000-11-01 2000-11-01
US09/703,771 2000-11-01
PCT/US2001/045704 WO2002036546A2 (en) 2000-11-01 2001-10-31 Alkynyl amides and their therapeutic applications

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CA2427560A1 true CA2427560A1 (en) 2002-05-10
CA2427560C CA2427560C (en) 2010-12-07

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EP (1) EP1330429A2 (en)
JP (1) JP4115835B2 (en)
AU (1) AU2002228726A1 (en)
CA (1) CA2427560C (en)
MX (1) MXPA03003926A (en)
PE (1) PE20020575A1 (en)
UY (1) UY26997A1 (en)
WO (1) WO2002036546A2 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2545771A1 (en) * 2003-11-12 2005-05-26 Nps Pharmaceuticals, Inc. Migraine treatments including isovaleramide compounds and serotonin agonists
DE102005062987A1 (en) * 2005-12-28 2007-07-05 Grünenthal GmbH New substituted propiolic acid amides, useful for treatment and prevention of e.g. pain, anxiety and panic attacks, are inhibitors of the mGluR5 receptor

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5585358A (en) * 1993-07-06 1996-12-17 Yissum Research Development Corporation Of The Hebrew University Of Jerusalem Derivatives of valproic acid amides and 2-valproenoic acid amides, method of making and use thereof as anticonvulsant agents

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WO2002036546A3 (en) 2002-10-10
JP4115835B2 (en) 2008-07-09
WO2002036546A2 (en) 2002-05-10
MXPA03003926A (en) 2004-05-24
JP2004532804A (en) 2004-10-28
AU2002228726A1 (en) 2002-05-15
CA2427560C (en) 2010-12-07
EP1330429A2 (en) 2003-07-30
UY26997A1 (en) 2002-07-31
PE20020575A1 (en) 2002-06-25

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