WO2000048584A2 - Aroyl aminoacyl pyrroles for use in the treatment of neuropathic pain - Google Patents
Aroyl aminoacyl pyrroles for use in the treatment of neuropathic pain Download PDFInfo
- Publication number
- WO2000048584A2 WO2000048584A2 PCT/US2000/004063 US0004063W WO0048584A2 WO 2000048584 A2 WO2000048584 A2 WO 2000048584A2 US 0004063 W US0004063 W US 0004063W WO 0048584 A2 WO0048584 A2 WO 0048584A2
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- WIPO (PCT)
- Prior art keywords
- ciph
- group
- methyl
- formula
- active compound
- Prior art date
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- 0 *c1c(C(C2=CCCC=C2)=O)[n](*)c(*)c1 Chemical compound *c1c(C(C2=CCCC=C2)=O)[n](*)c(*)c1 0.000 description 2
Classifications
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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]
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D401/06—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 only aliphatic carbon atoms
Definitions
- This invention relates to compounds useful in the treatment of neuropathic pain. More particularly, this invention relates to aroyl aminoacyl pyrroles that are useful in the treatment of neuropathic pain.
- neuropathic pain constitute an area of continuing medical need.
- Neuropathic pain is defined as pain caused by aberrant somatosensory processing in the peripheral or central nervous system.
- Chronic or debilitating conditions such as post-herpetic neuralgia and phantom limb syndrome, are categorized as neuropathic pain. Such conditions are widespread and cause unnecessary pain and suffering.
- current methods of treating neuropathic pain are often inadequate and result in huge medical costs.
- compositions of anticonvulsants and non-toxic NMDA (N-methyl-D-aspartate) antagonists in neuropathic pain-alleviating amounts have been shown to block a major intracellular consequence of NMDA receptor activation, Frank S. Caruso, et al., Pharmaceutical Compositions Containing Anticonvulsants and NMDA Receptor Antagonists for Treating Neuropathic Pain, WIPO Patent No. 98/07447.
- aroyl amino acyl pyrrole compounds of the present invention have been previously disclosed and taught as useful anticonvulsants, Richard J. Carmosin, John R. Carson, Philip M. Pitis, Anticonvulsant Aroyl Amino Acyl Pyrroles, US Patent No. 5,332,736.
- the compounds of the present invention have not previously been shown as effective for the treatment of neuropathic pain. It is an object of the present invention to teach a method for the treatment of neuropathic pain using the compounds of the present invention.
- neuropathic pain comprising the step of administering to a mammal suffering from such condition an effective amount, in a pharmaceutically acceptable carrier, of an active compound of the formula:
- n is an integer from 1 to 5;
- R1 is selected from the group consisting of H and Chalky!
- R2 and R3 are selected from the group consisting of H and C-j ⁇ alkyl; R 4 and R 5 are independently selected from the group consisting of H,
- Y is S or O
- x is 3 to 7 and R? is selected from the group consisting of methyl and hydroxymethyl
- R? is selected from the group consisting of methyl and hydroxymethyl
- R 6 is selected from the group consisting of halo, C-
- the compounds of the present invention used in the treatment of neuropathic pain may be placed into two categories, those having benzoyl at the 2-position and those having benzoyl at the 4-position. Both categories of compounds may be prepared by variations of what is fundamentally the same reaction scheme.
- Scheme 1 exemplifies the preparation of compounds having benzoyl at the 2-position.
- a simple pyrrole A1 is acylated with an appropriately substituted benzoyl chloride B1 to produce benzoyl pyrrole C1.
- This acylation may be carried out by simply heating the benzoyl chloride and the pyrrole in an aprotic solvent followed by removing excess benzoyl chloride by reaction with a dibasic amine and extraction with HCI.
- aprotic solvents which may be utilized are aromatic hydrocarbons, such as, benzene, toluene, xylene, chlorobenzene, nitrobenzene, etc.; paraffins, such as, methyl cyclohexane, octane, etc.; halocarbons, such as, methyl chloride, chloroform, tetrachloroethane, etc.; ethers, such as, diethyl ether, diglyme, etc.; ketones, such as, methyl ethyl ketone, cyclohexanone, etc.; esters, such as, ethyl butyrate, etc.; nitroalkanes, such as, nitropropane, etc.; or carbon disulfide.
- aromatic hydrocarbons such as, benzene, toluene, xylene, chlorobenzene, nitrobenzene, etc.
- paraffins such as, methyl cyclo
- the temperature of the acylation will vary depending upon the desired rate of reaction and the substituents of pyrrole A1. Preferably the acylation is carried out at a temperature of from about 50 to 250°C.
- a suitable dibasic amine is dimethyl-3- aminopropyl amine.
- R " 1 is hydrogen the acylation, as described, may not produce desirable yields.
- a Vilsmeier type acylation as employed by J. White and G. McGillivrey, J. Org. Chem., Vol. 42, pp 42-48, 1977 might be expeditiously employed.
- benzoyl pyrrole C1 is acylated at the 4-position in a Friedel-Crafts reaction with acid chloride D1 to produce 2-benzoyl-4-alkanoyl pyrrole E1.
- the Friedel-Crafts reaction is carried out by refluxing the carboxylic acid chloride D1 , in which X is Cl, Br or I, with product C1 in a solvent with a Friedel-Crafts reagent followed by treatment with HCI and evaporation of the solvent.
- Suitable Friedel-Crafts reagents include aluminum chloride, zinc chloride, BF3 or TiCl4.
- Suitable solvents include methylene chloride, 1 ,2-dichloroethane, carbon tetrachloride or chloroform.
- the temperature of reflux might vary between about 30 and
- Scheme 2 exemplifies the preparation of compounds having benzoyl at the 4-position. Except for the specifics of the reactants, each step of Scheme 2 is analogous to the corresponding step of Scheme 1 with the reactions and description thereof being identical.
- a simple pyrrole A2 is acylated with an appropriately substituted alkanoyl chloride B2 to produce alkanoyl pyrrole C2.
- alkanoyl pyrrole C2 is acylated at the 4-position in a Friedel-Crafts reaction with benzoic acid chloride D2 to produce 2-alkanoyl-4-benzoyl pyrrole E2.
- 2- alkanoyl-4-benzoyl pyrrole E2 is aminated with amine F2 to produce the desired 2-aminoalkanoyl-4-benzoyl pyrrole G2.
- Rl include hydrogen, methyl, ethyl, n-propyl and i-propyl. In the most preferred compounds, R1 is methyl.
- R ⁇ and R ⁇ include hydrogen, methyl, ethyl, n-propyl and i- propyl. In the most preferred compounds, R ⁇ and R3 are hydrogen and methyl.
- R ⁇ and R5> where independently selected, include hydrogen, methyl, ethyl, n-propyl, i-propyl, benzyl and 2-phenyleth-1 -yl where the phenyl ring may be mono- or di-substituted with a substituent selected from the group of methyl and methoxy.
- R ⁇ and R5, where independently selected, are hydrogen, methyl and in at most one instance benzyl.
- Preferred R ⁇ and R5, where fused and depicted together with nitrogen include 4-[bis(4-fluorophenyl)methylene]-piperidin-1-yl, 1 ,2,3,4-tetrahydro-6,7- dimethoxy-isoquinolin-2-yl,
- R ⁇ and R where fused and depicted together with nitrogen, are piperidine-1-yl, pyrrolidin-1-yl, morpholin-1-yl and imidazol-1-yl.
- R ⁇ include bromine, chlorine, methyl, ethyl, methoxy, ethoxy, hydroxy, nitro, amino, formylamino, acetylamino, cyano, perfluoromethyl, 3,3,3- trifluoropropyl, methylsulfonyl, methylsulfinyl, formyl, and acetyl.
- R is non-existent, methyl or chloro.
- the compounds herein readily form pharmaceutically acceptable acid addition salts.
- Such salts include hydrochlorides, sulfates, phosphates, methane sulfonates, fumarates, maleates, citrates, lactates, and the like. Those skilled in the art will readily recognize suitable methods for manufacture and use of the acid addition salts.
- the compounds of the present invention are useful in the treatment of neuropathic pain.
- the use of the compounds in treating neuropathic pain was determined using an animal model. This model was developed and first described by S. H. Chung and J. M. Chung, An Experimental Model for Peripheral Neuropathy Produced by Segmental Spinal Nerve Ligation in the Rat, Pain, 1992, 50, 355-363 (referred to hereinafter as the "Chung Model"). Male Sprague-Dawley rats, weighing approximately 200 g each were anesthetized with isoflurane. The spinal nerve at the level of L 5 was exposed through an incision just left of the dorsal midline and tightly ligated with 6-0 silk.
- the sham operation consisted of a similar surgery; the spinal nerve was visualized without being ligated. These animals were also tested for mechanical allodynia and showed no response to greater than 15 g of force applied to the ipsilateral paw.
- the results of the assay were expressed as percent of the maximum possible effect (% MPE), calculated as the PWT at the time of testing minus the baseline PWT divided by the maximum PWT (15 g) minus the baseline PWT times 100.
- the compounds of the present invention indicated in Table 1 were tested for activity against neuropathic pain by being dissolved or suspended in either water or hydroxypropyl methylcellulose, respectively. Postoperative animals between 14 to 42 days were fasted overnight prior to dosing. Animals were orally dosed and dosage volumes were calculated on a 4 mL/kg basis. The screening dose employed was 30 mg/kg.
- the compounds of the present invention listed in Table 1 include compounds of the formula: Table 1
- Ar, R 1 , R 2 , R 3 , R 4 and R 5 are selected concurrently from the group consisting of: Cpd # Ar R 1 R 2 R 3 R 4 , R 5 %MPE
- the results of the "Chung Model" study are statistically significant and suggest that the compounds of the present invention are effective in reducing neuropathic pain.
- the compounds of the present invention may be employed at a daily dosage in the range of about 30 to 2000 mg, usually in 2 to 4 divided doses, for an average adult human.
- a unit dose would contain about 10 to 500 mg of the active ingredient.
- the treatment would comprise the daily administration of from about 0.5 mg/kg to about 50 mg/kg.
- one or more compounds of the present invention are intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques, which carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral, by suppository, or parenteral.
- a pharmaceutical carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral, by suppository, or parenteral.
- any of the usual pharmaceutical media may be employed.
- suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like;
- suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar coated or enteric coated by standard techniques. Suppositories may be prepared, in which case cocoa butter could be used as the carrier.
- the carrier will usually comprise sterile water, though other ingredients, for example, for purposes such as aiding solubility or for preservation, may be included.
- injectable suspensions may also be prepared, in which case appropriate liquid carriers, suspending agents and the like may be employed.
- compositions herein will contain, per dosage unit, e.g., tablet, capsule, powder, injection, teaspoonful, suppository and the like, from about 10 to about 500 mg of the active ingredient.
- Example 3 By the procedure of Example 1 , employing the appropriate aroyl chloride in place of 4-methoxybenzoylchloride, the following products were produced: (2-chlorophenyl)(1 -methyl-1 H-pyrrol-2-yl)-methanone: mp 55-57°C ( 1 -methyl-1 H-pyrrol-2-yl)(4-nitrophenyl)-methanone: mp 148-150°C (3-chlorophenyl)(1 -methyl-1 H-pyrrol-2-yl)-methanone: bp 115-116°C (0.004 Torr).
- Example 3 (2-chlorophenyl)(1 -methyl-1 H-pyrrol-2-yl)-methanone: mp 55-57°C ( 1 -methyl-1 H-pyrrol-2-yl)(4-nitrophenyl)-methanone: mp 148-150°C (3-chlorophenyl)(1 -methyl-1 H-pyrrol-2-
- Example 8 Using the procedure of Example 6 and employing the appropriate aryl pyrrolyl methanone in place of (2,4-dichlorphenyl)(1 ,3,5-trimethyl-1 H-pyrrol-2-yl)- methanone and the approriate y-chloroacyl choride in place of chloroacetyl chloride, there were obtained the following products (8-1 through 8-9) having the formula:
- Ar, R 1 , R 2 , R 3 and n are selected concurrently from the group consisting of: o.
- Example 9 Using the procedure of Example 7 and employing the appropriate 1-(5- aroylpyrrol-3-yl)-y-chloroalkanone in place of 2-chloro-1-[5-(2,4- dichlorobenzoyl)-1 ,2,4-thmethyl-1 H-pyrrol-3-yl]-ethanone and the appropriate amine in place of piperidine, there were obtained the following products (9-1 through 9-42) having the formula:
- n, R 1 , R 2 , R 3 , R 4 , R 5 and Ar are selected concurrently from the group consisting of:
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK00911850T DK1154996T3 (en) | 1999-02-18 | 2000-02-17 | Aminoacylaroyl pyrrols for the treatment of neuropathic pain |
DE60006363T DE60006363T2 (en) | 1999-02-18 | 2000-02-17 | AMINOACYLAROYLPYRROLE FOR THE TREATMENT OF NEUROPATHIC PAIN |
AU33675/00A AU3367500A (en) | 1999-02-18 | 2000-02-17 | Aroyl aminoacyl pyrroles for use in the treatment of neuropathic pain |
CA002361390A CA2361390A1 (en) | 1999-02-18 | 2000-02-17 | Aroyl aminoacyl pyrroles for use in the treatment of neuropathic pain |
AT00911850T ATE253556T1 (en) | 1999-02-18 | 2000-02-17 | AMINOACYLAROYLPYRROLES FOR THE TREATMENT OF NEUROPATHIC PAIN |
EP00911850A EP1154996B1 (en) | 1999-02-18 | 2000-02-17 | Aroyl aminoacyl pyrroles for use in the treatment of neuropathic pain |
JP2000599376A JP2002537247A (en) | 1999-02-18 | 2000-02-17 | Aroylaminoacylpyrroles for use in treating neuropathic pain |
HK02102939.8A HK1041003B (en) | 1999-02-18 | 2002-04-18 | Aroyl aminoacyl pyrroles for use in the treatment of neuropathic pain |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12047799P | 1999-02-18 | 1999-02-18 | |
US60/120,477 | 1999-02-18 |
Publications (2)
Publication Number | Publication Date |
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WO2000048584A2 true WO2000048584A2 (en) | 2000-08-24 |
WO2000048584A3 WO2000048584A3 (en) | 2000-12-07 |
Family
ID=22390558
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/004063 WO2000048584A2 (en) | 1999-02-18 | 2000-02-17 | Aroyl aminoacyl pyrroles for use in the treatment of neuropathic pain |
Country Status (14)
Country | Link |
---|---|
US (2) | US6191142B1 (en) |
EP (1) | EP1154996B1 (en) |
JP (1) | JP2002537247A (en) |
AR (1) | AR022620A1 (en) |
AT (1) | ATE253556T1 (en) |
AU (1) | AU3367500A (en) |
CA (1) | CA2361390A1 (en) |
DE (1) | DE60006363T2 (en) |
DK (1) | DK1154996T3 (en) |
ES (1) | ES2209843T3 (en) |
HK (1) | HK1041003B (en) |
TR (1) | TR200103219T2 (en) |
TW (1) | TW562797B (en) |
WO (1) | WO2000048584A2 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002002521A2 (en) * | 2000-06-30 | 2002-01-10 | Ortho-Mcneil Pharmaceutical, Inc. | Aroyl aminoacyl pyrrole compounds and their pharmaceutical use |
WO2002057253A2 (en) * | 2000-12-20 | 2002-07-25 | Ortho-Mcneil Pharmaceutical, Inc. | Isoindolyl and isoquinolinyl aroyl pyrrole compounds for the treatment of central nervous system disorders |
WO2003057219A1 (en) * | 2001-12-27 | 2003-07-17 | Ortho-Mcneil Pharmaceutical Inc. | Aroyl pyrrole heteroeryl and methanols useful for treating a central nervous system disorder |
WO2003066040A1 (en) * | 2002-02-05 | 2003-08-14 | Ajinomoto Co.,Inc. | Medicinal compositions containing gabapentin or pregabalin and n-type calcium channel antagonist |
EP2256103A1 (en) | 2009-05-07 | 2010-12-01 | Biosynth AG | Novel indicator platform |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU230403B1 (en) * | 2003-12-19 | 2016-04-28 | Pál Kocsis | Pharmaceutical composition of a sodium channel blocker and a selective serotonin uptake inhibitor |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5332736A (en) * | 1993-11-01 | 1994-07-26 | Ortho Pharmaceutical Corporation | Anti-convulsant aroyl aminoacylpyrroles |
US5418236A (en) * | 1993-12-23 | 1995-05-23 | Ortho Pharmaceutical Corporation | Anxiolytic aroyl piperidinyl and piperazinylacyl pyrroles |
WO1998007447A1 (en) * | 1996-08-23 | 1998-02-26 | Algos Pharmaceutical Corporation | Anticonvulsant containing composition for treating neuropathic pain |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5760007A (en) | 1997-07-16 | 1998-06-02 | Ortho Pharmaceutical Corporation | Anticonvulsant derivatives useful in treating neuropathic pain |
-
2000
- 2000-02-17 CA CA002361390A patent/CA2361390A1/en not_active Abandoned
- 2000-02-17 EP EP00911850A patent/EP1154996B1/en not_active Expired - Lifetime
- 2000-02-17 ES ES00911850T patent/ES2209843T3/en not_active Expired - Lifetime
- 2000-02-17 AU AU33675/00A patent/AU3367500A/en not_active Abandoned
- 2000-02-17 DE DE60006363T patent/DE60006363T2/en not_active Expired - Lifetime
- 2000-02-17 WO PCT/US2000/004063 patent/WO2000048584A2/en active IP Right Grant
- 2000-02-17 TR TR2001/03219T patent/TR200103219T2/en unknown
- 2000-02-17 AT AT00911850T patent/ATE253556T1/en active
- 2000-02-17 US US09/505,916 patent/US6191142B1/en not_active Expired - Lifetime
- 2000-02-17 JP JP2000599376A patent/JP2002537247A/en active Pending
- 2000-02-17 AR ARP000100674A patent/AR022620A1/en unknown
- 2000-02-17 DK DK00911850T patent/DK1154996T3/en active
- 2000-03-23 TW TW089102769A patent/TW562797B/en not_active IP Right Cessation
-
2001
- 2001-02-05 US US09/777,087 patent/US6369228B2/en not_active Expired - Lifetime
-
2002
- 2002-04-18 HK HK02102939.8A patent/HK1041003B/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5332736A (en) * | 1993-11-01 | 1994-07-26 | Ortho Pharmaceutical Corporation | Anti-convulsant aroyl aminoacylpyrroles |
US5418236A (en) * | 1993-12-23 | 1995-05-23 | Ortho Pharmaceutical Corporation | Anxiolytic aroyl piperidinyl and piperazinylacyl pyrroles |
WO1998007447A1 (en) * | 1996-08-23 | 1998-02-26 | Algos Pharmaceutical Corporation | Anticonvulsant containing composition for treating neuropathic pain |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002002521A2 (en) * | 2000-06-30 | 2002-01-10 | Ortho-Mcneil Pharmaceutical, Inc. | Aroyl aminoacyl pyrrole compounds and their pharmaceutical use |
WO2002002521A3 (en) * | 2000-06-30 | 2002-04-04 | Ortho Mcneil Pharm Inc | Aroyl aminoacyl pyrrole compounds and their pharmaceutical use |
US6573267B2 (en) | 2000-06-30 | 2003-06-03 | Ortho-Mcneil Pharmaceutical, Inc. | Useful aroyl aminoacyl pyrrole compounds |
WO2002057253A2 (en) * | 2000-12-20 | 2002-07-25 | Ortho-Mcneil Pharmaceutical, Inc. | Isoindolyl and isoquinolinyl aroyl pyrrole compounds for the treatment of central nervous system disorders |
WO2002057253A3 (en) * | 2000-12-20 | 2002-10-24 | Ortho Mcneil Pharm Inc | Isoindolyl and isoquinolinyl aroyl pyrrole compounds for the treatment of central nervous system disorders |
WO2003057219A1 (en) * | 2001-12-27 | 2003-07-17 | Ortho-Mcneil Pharmaceutical Inc. | Aroyl pyrrole heteroeryl and methanols useful for treating a central nervous system disorder |
WO2003066040A1 (en) * | 2002-02-05 | 2003-08-14 | Ajinomoto Co.,Inc. | Medicinal compositions containing gabapentin or pregabalin and n-type calcium channel antagonist |
US7713957B2 (en) | 2002-02-05 | 2010-05-11 | Ajinomoto Co., Inc. | Pharmaceutical composition containing gabapentin or pregabalin and N-type calcium channel antagonist |
EP2256103A1 (en) | 2009-05-07 | 2010-12-01 | Biosynth AG | Novel indicator platform |
Also Published As
Publication number | Publication date |
---|---|
DE60006363T2 (en) | 2005-07-21 |
WO2000048584A3 (en) | 2000-12-07 |
ATE253556T1 (en) | 2003-11-15 |
EP1154996B1 (en) | 2003-11-05 |
HK1041003A1 (en) | 2002-06-28 |
CA2361390A1 (en) | 2000-08-24 |
ES2209843T3 (en) | 2004-07-01 |
TW562797B (en) | 2003-11-21 |
AU3367500A (en) | 2000-09-04 |
US6369228B2 (en) | 2002-04-09 |
TR200103219T2 (en) | 2002-04-22 |
US20010044452A1 (en) | 2001-11-22 |
JP2002537247A (en) | 2002-11-05 |
US6191142B1 (en) | 2001-02-20 |
EP1154996A2 (en) | 2001-11-21 |
AR022620A1 (en) | 2002-09-04 |
DE60006363D1 (en) | 2003-12-11 |
HK1041003B (en) | 2004-05-07 |
DK1154996T3 (en) | 2004-02-16 |
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