US20090088433A1 - Methods of using as analgesics 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds - Google Patents

Methods of using as analgesics 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds Download PDF

Info

Publication number
US20090088433A1
US20090088433A1 US11/814,604 US81460406A US2009088433A1 US 20090088433 A1 US20090088433 A1 US 20090088433A1 US 81460406 A US81460406 A US 81460406A US 2009088433 A1 US2009088433 A1 US 2009088433A1
Authority
US
United States
Prior art keywords
compound
threo
pharmaceutically acceptable
hydroxy
acceptable salt
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.)
Abandoned
Application number
US11/814,604
Other languages
English (en)
Inventor
Bertrand Leblond
Eric Beausoleil
Thierry Taverne
John E. Donello
Fabien (Jacques) Schweighoffer
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.)
Allergan Inc
Original Assignee
Allergan 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 Allergan Inc filed Critical Allergan Inc
Priority to US11/814,604 priority Critical patent/US20090088433A1/en
Assigned to ALLERGAN, INC. reassignment ALLERGAN, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SCHWEIGHOFFER, FABIEN, DONELLO, JOHN E., BEAUSOLEIL, ERIC, LEBLOND, BERTRAND, TAVERNE, THIERRY
Publication of US20090088433A1 publication Critical patent/US20090088433A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines 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
    • A61K31/495—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
    • 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
    • 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
    • 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
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
    • 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
    • C07D405/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings

Definitions

  • the present invention relates to methods of treating mammals in need of such treatment with an analgesics composition containing 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides or related compounds.
  • PDMP 1-Phenyl-2-decanoylamino-3-morpholino-1-propanol
  • glucosylceramide (GlcCer) formation by inhibiting the enzyme GlcCer synthase, thereby lowering the level of glycosphingolipids.)
  • the isomers most active have the R,R-(D-threo)-configuration. Four enantiomers are produced during the synthesis. Because only the D -threo enantiomers are active in inhibiting the glucosylceramide synthase, resolution of the active D -threo inhibitors was performed by chiral chromatography.
  • D-threo-PDMP has antitumor activity via inhibition of glycosphingolipid biosynthesis as described by Inokuchi J., Cancer Letters 38(1-2), 23-30, 1987.
  • D-threo-PDMP suppresses synaptic function by Mizutani A. et al., Biochem. Biophys. Res. Commun., 222, 494-498, 1996.
  • L-threo-PDMP is an agent for treating neuronal diseases WO 95/05177. This compound is also described to be an agent for protecting brain in U.S. Pat. No. 6,407,064. Moreover treatment with L-threo-PDMP after transient forebrain ischemia in rats ameliorated the deficit of a well learned spatial memory by an 8-arm maze task, suggesting a potential for neurodegenerative disorders as described by Inokuchi et al., Ann. N.Y. Acad. Sci., 845(1), 219-224, 1998 and JP 10324671 (Seikagaku Kogyo Co.).
  • a stereoselective synthesis of enantiomerically pure D-threo-PDMP has also been described by Shin, S. et al., Tetrahedron asymmetry, 11, 3293-3301, 2000 and WO 2002012185 the key step is the regioselective cleavage by nitrogen nucleophiles, as morpholine, of the C(3)—N-bond of non-activated enantiomerically pure aziridine-2-methanols.
  • L-threo-PDMP is an agent for treating neuronal diseases WO 95/05177. This compound is also described to be an agent for protecting brain in U.S. Pat. No. 6,407,064.
  • treatment with L-threo-PDMP after transient forebrain ischemia in rats ameliorated the deficit of a well learned spatial memory by an 8-arm maze task, suggesting a potential for neurodegenerative disorders as described by Inokuchi et al., Ann. N.Y. Acad. Sci., 845(1), 219-224, 1998 and JP 10324671 (Seikagaku Kogyo Co.).
  • PBPP D-threo-1-phenyl-2-benzyloxycarbonylamino-3-pyrrolidino-1-propanol
  • D-threo-P4 and its analogues from N-benzyloxycarbonyl-D-serine was described by Jimbo M. et al, J. Biochem., 127(3), 485-91, 2000 and EP 782992 (Seikagaku Kogyo Co.).
  • PBPP is described as a potent GCS inhibitor.
  • Novel prodrugs of P4 derivatives were described in US 20020198240 and WO 2002062777.
  • methyl isocyanoacetate CNCH 2 CO 2 Me was treated with pyrrolidine and the amide was treated with 1,4-benzodioxane-6-carboxaldehyde, followed by hydrolysis of the oxazoline using HCl in methanol, reduction of the keto group of amide II using LiAlH 4 , and acylation with palmitoyl chloride to give D,L-threo-ethylenedioxy-P4 III.
  • D-threo-ethylenedioxy-P4 was prepared via a multistep synthetic sequence starting from S-(+)-Ph glycinol, phenyl- ⁇ -bromoacetate, 1,4-benzodioxan-6-carboxaldehyde, pyrrolidine and palmitoyl chloride.
  • New D-threo-P4 analogues that bear ether substituents on the aromatic ring have been recently synthesized from D-serine and found to suppress neurite extension in an embryonic insect cell line as described by Slavish., J. P. et al., Bioorg. Med. Chem. Lett., 14, 1487-1490, 2004.
  • the present invention is directed to methods of using the compounds shown below as analgesics by administering to a mammal, in need of such administration a pharmaceutical composition containing one or more of the compounds or their pharmaceutically acceptable salts.
  • the present invention is still further directed to pharmaceutical compositions containing the compounds shown below and all other pharmaceutically acceptable salts of these compounds, to be used as analgesics.
  • the scope of the present invention includes use of the threo and erythro isomers, mixtures of erythro and threo isomers, both enantiomers of the isomers in optically pure form, racemic mixtures and mixtures where the enantiomers are not present in equal amounts.
  • the designation “DL” or “(+/ ⁇ )” or “( ⁇ )” in this application includes the pure dextrorotatory enantiomer, the pure levorotatory enantiomer and all racemic mixtures, including mixtures where the two enantiomers are present in equal or in unequal proportions.
  • the compounds used in the methods or compositions of the present invention may already be shown as hydrochloride salts.
  • the compounds may also exist in salt free form or may form salts with pharmaceutically acceptable acids, other than hydrochloric acid, and such pharmaceutically acceptable salts are also within the scope of the invention.
  • the compounds used in the method or compositions of the invention have analgesic activity in mammals.
  • An art-accepted model or assay for measuring an analgesic effect of a compound in chronic pain is the model known as Kim and Chung 1992, Pain 150, pp 355-363 (Chung model).
  • This model involves the surgical ligation of the L5 (and optionally the L6) spinal nerves on one side in experimental animals. Rats recovering from the surgery gain weight and display a level of general activity similar to that of normal rats. However, these rats develop abnormalities of the foot, wherein the hindpaw is moderately everted and the toes are held together. More importantly, the hindpaw on the side affected by the surgery appears to become sensitive to low-threshold mechanical stimuli and will perceive pain instead of the faint sensation of touch.
  • rats are anesthetized before surgery.
  • the surgical site is shaved and prepared either with betadine or Novacaine.
  • Incision is made from the thoracic vertebra Xlll down toward the sacrum.
  • Muscle tissue is separated from the spinal vertebra (left side) at the L4-S2 levels.
  • the L6 vertebra is located and the transverse process is carefully removed with a small rongeur to expose the L4-L6 spinal nerves.
  • the L5 and L6 spinal nerves are isolated and tightly ligated with 6-0 silk thread. The same procedure is done on the right side as a control, except no ligation of the spinal nerves is performed.
  • the wounds are sutured.
  • a small amount of antibiotic ointment is applied to the incised area, and the rat is transferred to the recovery plastic cage under a regulated heat-temperature lamp.
  • the test drugs are administered by intraperitoneal (i.p.) injection or oral gavage (p.o.).
  • i.p. administration the compounds are formulated in H 2 O and given in a volume of 1 ml/kg body weight by injecting into the intraperitoneal cavity.
  • p.o. administration the compounds are formulated in H 2 O and given in a volume of 1 ml/kg body weight using an 18-gauge, 3 inch gavage needle that is slowly inserted through the esophagus into the stomach.
  • Tactile allodynia is assessed via von Frey hairs, which are a series of fine hairs with incremental differences in stiffness. Rats are placed in a plastic cage with a wire mesh bottom and allowed to acclimate for approximately 30 minutes. To establish the pre-drug baseline, the von Frey hairs are applied perpendicularly through the mesh to the mid-plantar region of the rats' hindpaw with sufficient force to cause slight buckling and held for 6-8 seconds. The applied force has been calculated to range from 0.41 to 15.1 grams. If the paw is sharply withdrawn, it is considered a positive response. A normal animal will not respond to stimuli in this range, but a surgically ligated paw will be withdrawn in response to a 1-2 gram hair.
  • the 50% paw withdrawal threshold is determined using the method of Dixon, W. J., Ann. Rev. Pharmacol. Toxicol. 20:441-462 (1980) hereby incorporated by reference. Tactile allodynia is measured prior to and 15, 30, and 60 minutes after drug administration. The post-drug threshold is compared to the pre-drug threshold and the percent reversal of tactile sensitivity is calculated based on a normal threshold of 15.1 grams.
  • Table 1 below indicates the degree of pain reversal obtained in the Chung model with exemplary compounds used in accordance with the invention.
  • the intraperitonial (i.p.) and/or intravenous (iv) administration of the compounds was in doses ranging from 1 ⁇ g/kg to 300 ⁇ g/kg or 3 mg/kg PO and the peak percentage of reversal of allodynia was measured at 15, 30 or 60 minutes after administration, as is indicated in the table. Data are expressed as the highest % allodynia reversal (out of 3 time points: 15 min, 30 min, or 60 min. post-drug) with a minimum of a 20% allodynia reversal in the rat Chung model. Comparisons between groups (drug treated vs.
  • the compounds used in the methods and compositions of the invention are administered at pharmaceutically effective dosages.
  • dosages are normally the minimum dose necessary to achieve the desired therapeutic effect; in the treatment of chromic pain, this amount would be roughly that necessary to reduce the discomfort caused by the pain to tolerable levels.
  • doses generally will be in the range 0.1-5000 mg/day; more preferably in the range 1 to 3000 mg/day, still more preferably in the range of 10 mg to 1000 mg/day.
  • the actual amount of the compound to be administered in any given case will be determined by a physician taking into account the relevant circumstances, such as the severity of the pain, the age and weight of the patient, the patient's general physical condition, the cause of the pain, and the route of administration.
  • the patient will be given the compound in a composition orally in any pharmaceutically acceptable form, such as a tablet, liquid, capsule, powder and the like.
  • a composition orally in any pharmaceutically acceptable form, such as a tablet, liquid, capsule, powder and the like.
  • other routes may be desirable or necessary, particularly if the patient suffers from nausea.
  • Such other routes may include, without exception, transdermal, intraperitonial, parenteral, subcutaneous, intranasal, intrathecal, intramuscular, intravenous and intrarectal modes of delivery and the present invention extends to pharmaceutical compositions adapted for such deliveries.
  • Pharmaceutical compositions tend to contain a pharmaceutically acceptable excipient.
  • excipient are well known in the art and may be a carrier or a diluent; this is usually mixed with the active compound, or permitted to dilute or enclose the active compound.
  • the carrier may be solid, semi-solid, or liquid material that acts as an excipient or vehicle for the active compound.
  • the formulations of the compositions may also include wetting agents, emulsifying agents, preserving agents, sweetening agents, and/or flavoring agents. If used as in an ophthalmic or infusion format, the formulation will usually contain one or more salt to influence the osmotic pressure of the formulation.
  • the white suspension was then concentrated to remove THF and taken back up in a mixture of 300 mL CH 2 Cl 2 and 1N aqueous hydrochloric acid (50 mL).
  • the organic layer was removed, combined with additional CH 2 Cl 2 extracts (4 ⁇ 200 mL) and dried over MgSO 4 , filtered and evaporated.
  • a three neck, 250 mL round bottom flask was equipped with a low temperature thermometer and two (2) equalizing dropping funnels. One of these was connected to a nitrogen line and charged with a solution of ((R)-1-((S)-1-phenylethyl)aziridin-2-yl)methanol EBE 06046 (7.0 g, 39.5 mmol) in CH 2 Cl 2 (75 mL), the other was charged with a solution of DMSO (9.25 g, 118.5 mmol) in CH 2 Cl 2 (11 mL).
  • EBE 06070A the acetate salt of (2R)-amino-3-morpholin-4-yl-(1R)-phenyl-propan-1-ol (0.279 g, 98% yield).
  • solution of EBE 06070A the acetate salt of (2R)-amino-3-morpholin-4-yl-(1R)-phenyl-propan-1-ol (0.100 g, 0.338 mmol) in ethanol (1 mL) was added a solution of HCl (0.8 M, 0.930 mL) in EtOH.
  • PDMP 1-phenyl-2-decanoylamino-3-morpholino-1-propanol
  • Enantiomerically pure D-threo-PDMP has been reported by Mitchell, Scott A. [ J. Org. Chem., 63 (24), 8837-8842, 1998]; Miura, T. et al, [Bioorg. Med. Chem., 6, 1481-1498, 1998]; Shin, S. et al., [ Tetrahedron asymmetry, 11, 3293-3301, 2000]; WO 2002012185 which are incorporated herein by reference. Synthesis of enantiomerically pure L-threo-PDMP is described by Mitchell, Scott A., [ J. Org. Chem., 63 (24), 8837-8842, 1998]; Miura, T. et al, [Bioorg. Med. Chem., 6, 1481-1498, 1998]; and JP-A-9-216858, which are incorporated herein by reference.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Rheumatology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pyridine Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Quinoline Compounds (AREA)
  • Furan Compounds (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Hydrogenated Pyridines (AREA)
US11/814,604 2005-01-26 2006-01-25 Methods of using as analgesics 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds Abandoned US20090088433A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/814,604 US20090088433A1 (en) 2005-01-26 2006-01-25 Methods of using as analgesics 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US64727105P 2005-01-26 2005-01-26
US11/814,604 US20090088433A1 (en) 2005-01-26 2006-01-25 Methods of using as analgesics 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
PCT/US2006/002505 WO2006081252A2 (fr) 2005-01-26 2006-01-25 Methodes d'utilisation comme analgesiques de 1-benzyl-1-hydroxy-2, de 3-diamino-propyl amines, d'amides d'acide 3-benzyl-3-hydroxy-2-amino-propionique et de leurs composes

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/002505 A-371-Of-International WO2006081252A2 (fr) 2005-01-26 2006-01-25 Methodes d'utilisation comme analgesiques de 1-benzyl-1-hydroxy-2, de 3-diamino-propyl amines, d'amides d'acide 3-benzyl-3-hydroxy-2-amino-propionique et de leurs composes

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/450,854 Division US9278943B2 (en) 2005-01-26 2012-04-19 Methods of using as analgesics 1-benzyl-1-hydroxy-2, 3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds

Publications (1)

Publication Number Publication Date
US20090088433A1 true US20090088433A1 (en) 2009-04-02

Family

ID=36250723

Family Applications (11)

Application Number Title Priority Date Filing Date
US11/814,604 Abandoned US20090088433A1 (en) 2005-01-26 2006-01-25 Methods of using as analgesics 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
US11/814,593 Active 2027-06-18 US8153666B2 (en) 2005-01-26 2006-01-25 Compounds having analgesic and/or immunostimulant activity
US11/814,598 Active 2028-09-15 US8288556B2 (en) 2005-01-26 2006-01-25 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic and/or immuno stimulant activity
US11/814,601 Active 2027-08-16 US8013000B2 (en) 2005-01-26 2006-01-25 3-heteroaryl-3-hydroxy-2-amino-propyl amines and related compounds having analgesic and/or immuno stimlant activity
US13/196,132 Active US8513288B2 (en) 2005-01-26 2011-08-02 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and related compounds having analgesic and/or immuno stimulant activity
US13/409,853 Active 2026-09-08 US8835463B2 (en) 2005-01-26 2012-03-01 Compounds having analgesic and/or immunostimulant activity
US13/450,854 Active US9278943B2 (en) 2005-01-26 2012-04-19 Methods of using as analgesics 1-benzyl-1-hydroxy-2, 3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
US13/612,260 Active US8431599B2 (en) 2005-01-26 2012-09-12 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic and/or immuno stimulant activity
US13/834,336 Active US8927589B2 (en) 2005-01-26 2013-03-15 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-aminopropionic acid amides and related compounds having analgesic and/or immuno stimulant activity
US13/949,468 Active US9399628B2 (en) 2005-01-26 2013-07-24 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and related compounds having analgesic and/or immuno stimulant activity
US14/954,263 Active US9828349B2 (en) 2005-01-26 2015-11-30 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and related compounds having analgesic and/or immuno stimulant activity

Family Applications After (10)

Application Number Title Priority Date Filing Date
US11/814,593 Active 2027-06-18 US8153666B2 (en) 2005-01-26 2006-01-25 Compounds having analgesic and/or immunostimulant activity
US11/814,598 Active 2028-09-15 US8288556B2 (en) 2005-01-26 2006-01-25 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic and/or immuno stimulant activity
US11/814,601 Active 2027-08-16 US8013000B2 (en) 2005-01-26 2006-01-25 3-heteroaryl-3-hydroxy-2-amino-propyl amines and related compounds having analgesic and/or immuno stimlant activity
US13/196,132 Active US8513288B2 (en) 2005-01-26 2011-08-02 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and related compounds having analgesic and/or immuno stimulant activity
US13/409,853 Active 2026-09-08 US8835463B2 (en) 2005-01-26 2012-03-01 Compounds having analgesic and/or immunostimulant activity
US13/450,854 Active US9278943B2 (en) 2005-01-26 2012-04-19 Methods of using as analgesics 1-benzyl-1-hydroxy-2, 3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
US13/612,260 Active US8431599B2 (en) 2005-01-26 2012-09-12 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic and/or immuno stimulant activity
US13/834,336 Active US8927589B2 (en) 2005-01-26 2013-03-15 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-aminopropionic acid amides and related compounds having analgesic and/or immuno stimulant activity
US13/949,468 Active US9399628B2 (en) 2005-01-26 2013-07-24 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and related compounds having analgesic and/or immuno stimulant activity
US14/954,263 Active US9828349B2 (en) 2005-01-26 2015-11-30 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and related compounds having analgesic and/or immuno stimulant activity

Country Status (20)

Country Link
US (11) US20090088433A1 (fr)
EP (7) EP2474534B1 (fr)
JP (6) JP5042040B2 (fr)
KR (1) KR101395382B1 (fr)
CN (2) CN102718748B (fr)
AT (3) ATE460159T1 (fr)
AU (4) AU2006209208B2 (fr)
BR (5) BRPI0607304A2 (fr)
CA (4) CA2595522C (fr)
DE (1) DE602006012801D1 (fr)
DK (3) DK1841423T3 (fr)
ES (5) ES2565236T3 (fr)
HK (2) HK1145628A1 (fr)
HU (1) HUE028654T2 (fr)
MX (1) MX2007008955A (fr)
NZ (1) NZ556614A (fr)
PL (2) PL1841743T3 (fr)
RU (1) RU2433999C2 (fr)
WO (4) WO2006081252A2 (fr)
ZA (1) ZA200706010B (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100113433A1 (en) * 2007-04-03 2010-05-06 Song Li N-Substituted Thiomorpholine Derivatives as the Inhibitors of Dipeptidyl Peptidase IV and the Pharmaceutical Uses Thereof

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8003617B2 (en) 2004-11-10 2011-08-23 Genzyme Corporation Methods of treating diabetes mellitus
BRPI0607304A2 (pt) * 2005-01-26 2009-08-25 Allergan Inc compostos tendo atividade analgésica e/ou imunoestimulante
PT2032134E (pt) 2006-05-09 2015-10-07 Genzyme Corp Métodos de tratamento da doença do fígado gorduroso
WO2008011485A2 (fr) * 2006-07-19 2008-01-24 Allergan, Inc. Méthodes de traitement de la douleur chronique
WO2008011487A2 (fr) * 2006-07-19 2008-01-24 Allergan, Inc. Procédés pour le traitement de la douleur chronique à l'aide de 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, d'amides d'acide 3-benzyl-3-hydroxy-2-amino-propioniques et de composés apparentés
WO2008011478A2 (fr) * 2006-07-19 2008-01-24 Allergan, Inc. Procédés de traitement de douleur chronique utilisant des amides d'acide 3-aryl-3-hydroxy-2-amino-propioniques, amides d'acide 3-hétéroaryl-3-hydroxy-2-amino-propionique et composés connexes
WO2008011483A2 (fr) * 2006-07-19 2008-01-24 Allergan, Inc. Procédés de traitement de la douleur chronique à l'aide de 1-aryl-1-hydroxy 2,3-diamino-propyl amines, de 1-hétéroaryl-1-hydroxy-2,3-diamino-propyl amines et de composés apparentés
US20140179925A1 (en) 2009-09-04 2014-06-26 Allergan, Inc. Methods for treating cognitive disorders using 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds
US8173683B2 (en) 2007-03-06 2012-05-08 Allergan, Inc. Methods for treating cognitive disorders
US9314466B2 (en) 2007-03-06 2016-04-19 Allergan, Inc. Methods for treating cognitive disorders using 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
WO2008109610A1 (fr) 2007-03-06 2008-09-12 Allergan, Inc. Procédés de traitement des troubles cognitifs au moyen d'amides d'acides 3-aryl-3-hydroxy-2-amino-propioniques, d'amides d'acides 3-hétéroaryl-3-hydroxy-2-amino-propioniques et de composés apparentés
EP2594565B1 (fr) 2007-05-31 2018-10-24 Genzyme Corporation Inhibiteurs de glucosylcéramide synthase de type 2-acylaminopropanol
RU2491931C2 (ru) * 2007-07-17 2013-09-10 Аллерган, Инк. Способы лечения тревоги
EP2209473B1 (fr) 2007-10-05 2017-11-22 Genzyme Corporation Procédé utilisant des dérivés de céramide pour traiter des maladies polykystiques des reins
US8168631B2 (en) 2008-02-05 2012-05-01 Allergan, Inc. 3-(4-fluorophenyl)-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic activity
US8389517B2 (en) 2008-07-28 2013-03-05 Genzyme Corporation Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease
MX2011003517A (es) 2008-10-03 2011-05-25 Genzyme Corp Inhibidores de la glucosilceramida sintasa tipo 2-acilaminopropanol.
EP2453890B1 (fr) * 2009-07-17 2020-05-27 Allergan, Inc. Compositions comprenant un inhibiteur de la cholinestérase pour traiter des troubles cognitifs
WO2011034915A1 (fr) * 2009-09-16 2011-03-24 Allergan, Inc. Compositions et procédés de traitement de troubles de la motilité gastro-intestinale
ES2440068T3 (es) 2009-09-16 2014-01-27 Allergan, Inc. Compuestos para su uso en el tratamiento de trastornos convulsivos
CA2774355A1 (fr) 2009-09-16 2011-03-24 Allergan, Inc. Compositions et procedes de traitement de la spasticite
AU2010320963B2 (en) 2009-11-18 2015-07-09 Fab Pharma Sas Novel heterocyclic acrylamides and their use as pharmaceuticals
EP3336079A1 (fr) * 2013-08-15 2018-06-20 Allergan, Inc. Sel de tartrate de (-)-(2r,3s)-2-amino-3-hydroxy-3-pyridin-4-yl-1-pyrrolidin-1-yl-propan-1-one (l)-(+), son procédé de production et utilisation
JP6537500B2 (ja) 2013-09-20 2019-07-03 ビオマリン プハルマセウトイカル インコーポレイテッド 疾患治療用のグルコシルセラミドシンターゼ阻害剤
JP6152816B2 (ja) * 2014-03-26 2017-06-28 ソニー株式会社 半導体デバイス、表示パネル、表示装置、電子装置、および、半導体デバイスの製造方法
DE102015217629A1 (de) * 2015-09-15 2017-03-16 Tridonic Gmbh & Co Kg PFC-Modul für lückenden Betrieb

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5767121A (en) * 1991-05-10 1998-06-16 Takeda Chemical Industries, Ltd. Pyridine derivatives, their production and use
US5916911A (en) * 1995-09-20 1999-06-29 The Regents Of The University Of Michigan Amino ceramide--like compounds and therapeutic methods of use
US5976781A (en) * 1994-09-19 1999-11-02 The Board Of Trustees Of The Leland Stanford Junior University Determining plasmodium in blood by sphingomyelin synthase activity
US6407064B2 (en) * 1999-12-06 2002-06-18 Seikagaku Corporation Aminoalcohol derivative and medicament comprising the same
US20020198240A1 (en) * 2001-01-10 2002-12-26 Shayman James A. Amino ceramide - like compounds and therapeutic methods of use
US20030050299A1 (en) * 2001-07-16 2003-03-13 Genzyme Corporation Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors

Family Cites Families (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2514380A (en) * 1946-12-26 1950-07-11 Hoffmann La Roche Diamines and method of production
DE1001261C2 (de) * 1954-08-05 1957-07-04 Thomae Gmbh Dr K Verfahren zur Herstellung von basischen Estern endocyclisch substituierter Mandelsaeuren und ihren Salzen
US2918466A (en) * 1955-05-24 1959-12-22 Univ St Johns Antimicrobial chemical compounds derived from alkoxyphenyl glycidic acid
US3065265A (en) * 1957-07-04 1962-11-20 Hoffmann La Roche Amino acid hydrazides
SU1063026A1 (ru) 1982-05-19 1990-12-07 Институт биохимии АН ЛитССР N @ -Бензолсульфонильные производные трес-DL-фенилсерина, обладающие противовоспалительной активностью
EP0144290A3 (fr) * 1983-12-01 1987-05-27 Ciba-Geigy Ag Dérivés éthylènediamine substitués
JPS60132935A (ja) 1983-12-20 1985-07-16 Sumitomo Chem Co Ltd フエニルセリン誘導体及びその製造方法
JPS61145148A (ja) 1984-12-19 1986-07-02 Sumitomo Seiyaku Kk フエニルセリン誘導体
GB8618188D0 (en) * 1986-07-25 1986-09-03 Ici Plc Diamine compounds
GB8622352D0 (en) * 1986-09-17 1986-10-22 Zambeleetti Spa Dr L Compounds
JPH02250845A (ja) 1989-03-22 1990-10-08 Sumitomo Pharmaceut Co Ltd ３―（４―フルオロフェニル）プロピオンアルデヒドの製造方法
JPH0550499A (ja) 1991-08-27 1993-03-02 Kuwabara Yasunaga 成形型内におけるトリミング方法及び容器
US6696486B1 (en) * 1992-01-22 2004-02-24 Glaxo Group Limited Medical use for atypical β-adrenoceptor agonists
DE69426331T2 (de) * 1993-08-13 2001-06-21 Seikagaku Kogyo Co Ltd Arzneimittel gegen nervöse erkrankungen
WO1995016786A1 (fr) 1993-12-17 1995-06-22 Dsm N.V. Amides de phenylserine et preparation de phenylserines/amides de phenylserine
US5763438A (en) * 1994-06-10 1998-06-09 Seikagaku Corporation 2-acylaminopropanol compound and medical composition
US5585388A (en) * 1995-04-07 1996-12-17 Sibia Neurosciences, Inc. Substituted pyridines useful as modulators of acetylcholine receptors
FR2732894B1 (fr) 1995-04-13 1997-07-04 Sanofi Sa Nouvelle utilisation de composes agonistes beta9-adrenergiques
JPH08337569A (ja) * 1995-06-15 1996-12-24 Sankyo Co Ltd 鎮痛活性物質
WO2001004108A1 (fr) 1999-07-09 2001-01-18 Regents Of The University Of Michigan Composes de type amino-ceramide et procedes therapeutiques d'utilisation
NO965193L (no) * 1995-12-08 1997-06-09 Seikagaku Kogyo Kk Seikagaku C Aminalkoholderivat og fremgangsmåte for fremstilling derav
JP3993908B2 (ja) * 1995-12-08 2007-10-17 生化学工業株式会社 アミノアルコール誘導体及び該誘導体の製造方法
DE19601745C1 (de) 1996-01-19 1997-10-09 Gruenenthal Gmbh Verfahren zur Racematspaltung von Tramadol
EP0848059A1 (fr) * 1996-12-12 1998-06-17 Vetigen Récepteur ICYP (Iodocyanopindolol) de mammifères et ses applications
AU5923998A (en) * 1997-01-31 1998-08-25 Avid Therapeutics Inc. 2-benzoylamino-3-phenylpropenamide derivatives and methods of using the same
AU6867498A (en) 1997-03-21 1998-10-20 Scripps Research Institute, The Synthesis of alpha,beta-substituted amino amides, esters and acids
JP4036500B2 (ja) 1997-05-23 2008-01-23 生化学工業株式会社 アミノアルコール誘導体及びそれを含有する医薬
US6617340B1 (en) * 1999-07-29 2003-09-09 Novartis Ag N-(substituted glycyl)-pyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
SE9904197D0 (sv) 1999-11-22 1999-11-22 Amersham Pharm Biotech Ab A method for anion exchange adsorption on matrices carrying mixed mode ligands
AU2207001A (en) * 1999-12-24 2001-07-09 Smithkline Beecham Plc Novel compounds and process
US6380398B2 (en) * 2000-01-04 2002-04-30 Novo Nordisk A/S Therapeutically active and selective heterocyclic compounds that are inhibitors of the enzyme DPP-IV
GB0010188D0 (en) * 2000-04-26 2000-06-14 Ferring Bv Inhibitors of dipeptidyl peptidase IV
KR20000063913A (ko) 2000-08-10 2000-11-06 하현준 아지리딘으로부터 1,2-디아미노프로판 알코올을 제조하는방법
WO2002062777A2 (fr) 2001-01-10 2002-08-15 The Regents Of The University Of Michigan Composes du type amino-ceramide et procedes therapeutiques d'utilisation
CA2462200A1 (fr) * 2001-08-10 2003-02-20 Palatin Technologies, Inc. Peptidomimetiques de metallopeptides biologiquement actifs
AU2002348261A1 (en) 2001-11-26 2003-06-10 Genzyme Corporation Diastereoselective synthesis of udp-glucose : n-acylsphingosine glucosyltransferase inhibitors
JP2006021997A (ja) 2002-07-09 2006-01-26 Ono Pharmaceut Co Ltd ｃｙｓＬＴ１／ｃｙｓＬＴ２両受容体拮抗性呼吸器疾患治療剤
EP1578414A4 (fr) * 2002-12-04 2007-10-24 Merck & Co Inc Derives de phenylalanine utilises comme inhibiteurs de la dipeptidylpeptisase pour le traitement ou la prevention de diabetes
MXPA05007394A (es) 2003-01-08 2005-09-12 Chiron Corp Agentes antibacterianos.
JP4704914B2 (ja) * 2003-12-11 2011-06-22 田辺三菱製薬株式会社 α−アミノ酸誘導体及びその医薬用途
MXPA06007378A (es) 2003-12-23 2007-01-26 Musc Found For Res Dev Metodos y composiciones para la prevencion y tratamiento de enfermedades o condiciones inflamatorias.
US20070093492A1 (en) * 2004-03-09 2007-04-26 Weir-Torn Jiaang Pyrrolidine derivatives
US20080221203A1 (en) 2004-08-09 2008-09-11 University Catholique De Louvain Use of Agonists and Antagonists of Beta Adrenoceptors for Treating Arterial Disease
DE102004053409A1 (de) 2004-11-05 2006-05-11 Bayer Healthcare Ag Verfahren zur gezielten Herstellung von Lysobactinfragmenten
BRPI0607304A2 (pt) 2005-01-26 2009-08-25 Allergan Inc compostos tendo atividade analgésica e/ou imunoestimulante
US7858825B2 (en) * 2007-02-15 2010-12-28 Colorado State University Research Foundation Acid and base stable diphenylmethanol derivatives and methods of use
US8173683B2 (en) * 2007-03-06 2012-05-08 Allergan, Inc. Methods for treating cognitive disorders
WO2008109286A1 (fr) * 2007-03-06 2008-09-12 Allergan, Inc. Procédés de traitement de troubles cognitifs utilisant les 1-aryl-1-hydroxy-2,3-diamino-propyl amines, les 1-hétéroaryl-1-hydroxy-2,3-diamino-propyl amines et les composés apparentés
WO2008109610A1 (fr) * 2007-03-06 2008-09-12 Allergan, Inc. Procédés de traitement des troubles cognitifs au moyen d'amides d'acides 3-aryl-3-hydroxy-2-amino-propioniques, d'amides d'acides 3-hétéroaryl-3-hydroxy-2-amino-propioniques et de composés apparentés
RU2491931C2 (ru) * 2007-07-17 2013-09-10 Аллерган, Инк. Способы лечения тревоги
US8168631B2 (en) 2008-02-05 2012-05-01 Allergan, Inc. 3-(4-fluorophenyl)-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic activity
US8124648B2 (en) * 2008-05-20 2012-02-28 Allergan, Inc. Therapeutic lactams
WO2011034915A1 (fr) * 2009-09-16 2011-03-24 Allergan, Inc. Compositions et procédés de traitement de troubles de la motilité gastro-intestinale
CA2774355A1 (fr) * 2009-09-16 2011-03-24 Allergan, Inc. Compositions et procedes de traitement de la spasticite
ES2440068T3 (es) * 2009-09-16 2014-01-27 Allergan, Inc. Compuestos para su uso en el tratamiento de trastornos convulsivos

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5767121A (en) * 1991-05-10 1998-06-16 Takeda Chemical Industries, Ltd. Pyridine derivatives, their production and use
US5976781A (en) * 1994-09-19 1999-11-02 The Board Of Trustees Of The Leland Stanford Junior University Determining plasmodium in blood by sphingomyelin synthase activity
US5916911A (en) * 1995-09-20 1999-06-29 The Regents Of The University Of Michigan Amino ceramide--like compounds and therapeutic methods of use
US5945442A (en) * 1995-09-20 1999-08-31 The Regents Of The University Of Michigan Amino ceramide-like compounds and therapeutic methods of use
US5952370A (en) * 1995-09-20 1999-09-14 The Regents Of University Of Michigan Amino ceramide-like compounds and therapeutic methods of use
US6030995A (en) * 1995-09-20 2000-02-29 The Regents Of The University Of Michigan Amino ceramide-like compounds and therapeutic methods of use
US6051598A (en) * 1995-09-20 2000-04-18 The Regents Of The University Of Michigan Amino ceramide-like compounds and therapeutic methods of use
US6407064B2 (en) * 1999-12-06 2002-06-18 Seikagaku Corporation Aminoalcohol derivative and medicament comprising the same
US20020198240A1 (en) * 2001-01-10 2002-12-26 Shayman James A. Amino ceramide - like compounds and therapeutic methods of use
US20030050299A1 (en) * 2001-07-16 2003-03-13 Genzyme Corporation Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100113433A1 (en) * 2007-04-03 2010-05-06 Song Li N-Substituted Thiomorpholine Derivatives as the Inhibitors of Dipeptidyl Peptidase IV and the Pharmaceutical Uses Thereof
US8173643B2 (en) 2007-04-03 2012-05-08 Beijing Molecule Science And Technology Co., Ltd. N-substituted thiomorpholine derivatives as the inhibitors of dipeptidyl peptidase IV and the pharmaceutical uses thereof

Also Published As

Publication number Publication date
US20130202653A1 (en) 2013-08-08
US8513288B2 (en) 2013-08-20
DE602006012801D1 (de) 2010-04-22
US8835463B2 (en) 2014-09-16
US20120225881A1 (en) 2012-09-06
CA2595544A1 (fr) 2006-08-03
WO2006081252A3 (fr) 2006-12-28
AU2006209207A1 (en) 2006-08-03
CN102718748B (zh) 2016-06-22
ES2436612T3 (es) 2014-01-03
US20160083371A1 (en) 2016-03-24
ES2380904T3 (es) 2012-05-21
WO2006081276A8 (fr) 2007-05-03
WO2006081280A1 (fr) 2006-08-03
EP1841423B1 (fr) 2010-03-10
RU2007128313A (ru) 2009-03-10
US8013000B2 (en) 2011-09-06
HK1173721A1 (en) 2013-05-24
JP2012162546A (ja) 2012-08-30
EP1841742B1 (fr) 2013-10-30
JP5107058B2 (ja) 2012-12-26
PL1841743T3 (pl) 2016-06-30
DK1841756T3 (da) 2011-10-17
EP2198864B1 (fr) 2012-03-14
CA2595522C (fr) 2013-09-10
AU2006209207C1 (en) 2013-05-23
BRPI0607379B1 (pt) 2020-06-30
JP5042039B2 (ja) 2012-10-03
BRPI0606112B8 (pt) 2021-05-25
BRPI0607379B8 (pt) 2021-05-25
BRPI0607379A2 (pt) 2009-09-01
CA2595542A1 (fr) 2006-08-03
KR20070098946A (ko) 2007-10-05
BRPI0606112A2 (pt) 2009-06-02
ATE523491T1 (de) 2011-09-15
HUE028654T2 (en) 2016-12-28
JP2008528596A (ja) 2008-07-31
JP5039564B2 (ja) 2012-10-03
US20130005717A1 (en) 2013-01-03
ES2565236T3 (es) 2016-04-01
WO2006081273A8 (fr) 2007-03-01
AU2006209209A1 (en) 2006-08-03
CN101151248B (zh) 2012-06-20
US9399628B2 (en) 2016-07-26
US8431599B2 (en) 2013-04-30
ATE549020T1 (de) 2012-03-15
EP1841423A2 (fr) 2007-10-10
WO2006081252A2 (fr) 2006-08-03
DK1841743T3 (en) 2016-03-14
CA2595544C (fr) 2013-04-02
KR101395382B1 (ko) 2014-05-14
CA2595522A1 (fr) 2006-08-03
US20120157497A1 (en) 2012-06-21
US20110288094A1 (en) 2011-11-24
JP2008528600A (ja) 2008-07-31
WO2006081273A1 (fr) 2006-08-03
DK1841423T3 (da) 2010-06-07
EP1841756A1 (fr) 2007-10-10
AU2006209207B2 (en) 2012-08-23
JP2012162547A (ja) 2012-08-30
EP1841742A1 (fr) 2007-10-10
JP5042040B2 (ja) 2012-10-03
HK1145628A1 (en) 2011-04-29
AU2006209209B2 (en) 2012-07-19
MX2007008955A (es) 2007-09-18
BRPI0606112B1 (pt) 2021-02-23
ATE460159T1 (de) 2010-03-15
BRPI0606111B8 (pt) 2021-05-25
JP2008528601A (ja) 2008-07-31
EP1841743A1 (fr) 2007-10-10
WO2006081276A1 (fr) 2006-08-03
US20130310383A1 (en) 2013-11-21
AU2006209208A1 (en) 2006-08-03
BRPI0606111A2 (pt) 2009-06-02
US20090318499A1 (en) 2009-12-24
ES2371265T3 (es) 2011-12-29
US8288556B2 (en) 2012-10-16
US9828349B2 (en) 2017-11-28
CN102718748A (zh) 2012-10-10
BR122018068138B1 (pt) 2021-09-08
US20090036436A1 (en) 2009-02-05
NZ556614A (en) 2010-10-29
PL383715A1 (pl) 2008-05-12
BRPI0606111B1 (pt) 2020-12-15
CA2595519C (fr) 2013-10-29
BR122018068138B8 (pt) 2022-02-08
US8927589B2 (en) 2015-01-06
EP2489658B1 (fr) 2014-04-09
AU2006209197A1 (en) 2006-08-03
CN101151248A (zh) 2008-03-26
EP1841756B1 (fr) 2011-09-07
AU2006209208B2 (en) 2012-08-23
EP2489658A1 (fr) 2012-08-22
US20080312236A1 (en) 2008-12-18
EP2474534B1 (fr) 2015-07-29
EP1841743B1 (fr) 2016-01-20
US8153666B2 (en) 2012-04-10
JP2008528602A (ja) 2008-07-31
EP2198864A1 (fr) 2010-06-23
ES2340196T3 (es) 2010-05-31
CA2595519A1 (fr) 2006-08-03
US9278943B2 (en) 2016-03-08
ZA200706010B (en) 2009-04-29
BRPI0607304A2 (pt) 2009-08-25
RU2433999C2 (ru) 2011-11-20
EP2474534A1 (fr) 2012-07-11

Similar Documents

Publication Publication Date Title
US9278943B2 (en) Methods of using as analgesics 1-benzyl-1-hydroxy-2, 3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
WO2008011487A2 (fr) Procédés pour le traitement de la douleur chronique à l'aide de 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, d'amides d'acide 3-benzyl-3-hydroxy-2-amino-propioniques et de composés apparentés
US20100105687A1 (en) Methods for treating cognitive disorders using 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and related compounds
US20100190792A1 (en) Methods for treating cognitive disorders using 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
US9314466B2 (en) Methods for treating cognitive disorders using 1-benzyl-1-hydroxy-2,3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds
AU2012201628A1 (en) Use of 1-benzyl-1-hydroxy-2, 3-diamino-propyl amines, 3-benzyl-3-hydroxy-2-amino-propionic acid amides and related compounds as analgesics
AU2012208996A1 (en) 3-heteroaryl-3-hydroxy-2-amino-propyl amines and related compounds having analgesic and/or immuno stimulant activity

Legal Events

Date Code Title Description
AS Assignment

Owner name: ALLERGAN, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BEAUSOLEIL, ERIC;LEBLOND, BERTRAND;TAVERNE, THIERRY;AND OTHERS;REEL/FRAME:019619/0169;SIGNING DATES FROM 20050225 TO 20070727

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION