WO1996037489A1 - 1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists - Google Patents
1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists Download PDFInfo
- Publication number
- WO1996037489A1 WO1996037489A1 PCT/JP1996/001335 JP9601335W WO9637489A1 WO 1996037489 A1 WO1996037489 A1 WO 1996037489A1 JP 9601335 W JP9601335 W JP 9601335W WO 9637489 A1 WO9637489 A1 WO 9637489A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- salt
- alkyl
- formula
- acid
- Prior art date
Links
- SSOTVEFZSPRUME-MIJJZIGMSA-N Cc1cc(C([N](C2)(CC3)C2[C@H](Cc2ccccc2)CN3C(Cc2c[nH]c3c2cccc3)=O)=O)cc(C(F)(F)F)c1 Chemical compound Cc1cc(C([N](C2)(CC3)C2[C@H](Cc2ccccc2)CN3C(Cc2c[nH]c3c2cccc3)=O)=O)cc(C(F)(F)F)c1 SSOTVEFZSPRUME-MIJJZIGMSA-N 0.000 description 1
Classifications
-
- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Definitions
- the present invention relates to new piperazine
- composition comprising the same, and to a use of the same as a medicament.
- one object of the present invention is to provide new and useful piperazine derivatives and a
- Tachykinin antagonism especially Substance P antagonism, Neurokinin A antagonism, Neurokinin B antagonism, and the like.
- Another object of the present invention is to provide a process for the preparation of said piperazine derivatives and a salt thereof.
- a further object of the present invention is to provide a pharmaceutical composition comprising, as an active
- Still further object of the present invention is to provide a use of said piperazine derivatives or a
- Substance P antagonist especially Substance P antagonist, Neurokinin A antagonist or Neurokinin B antagonist, useful for treating or preventing Tachykinin-mediated diseases, for example,
- respiratory diseases such as asthma, bronchitis, rhinitis, cough, expectoration, and the like; ophthalmic diseases such as conjunctivitis, vernal conjunctivitis, and the like;
- cutaneous diseases such as contact dermatitis, atopic
- dermatitis urticaria, and other eczematoid dermatitis, and the like; inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and the like; pains or aches (e.g., migraine, headache, toothache cancerous pain, back pain, etc.); and the like in human being or animals.
- inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and the like
- pains or aches e.g., migraine, headache, toothache cancerous pain, back pain, etc.
- the object compound of the present invention is the compound of the following formula (I):
- the other object compound of the present invention can be represented by the following general formula (Ig) :
- R 1 is trihalo (lower) alkyl
- R 2 is trihalo (lower) alkyl
- R 3 is indolyl (lower) alkyl
- R 5 is hydrogen or lower alkoxycarbonyl
- R 6 is hydrogen or lower alkanoyl
- R 7 is hydrogen, lower alkyl, lower alkanoyl, lower
- alkoxycarbonyl lower alkoxy (lower) alkanoyl, cyclo (lower) alkylcarbonyl, aroyl or lower alkylsulfonyl,
- the object compounds can be prepared by processes which are illustrated in the following schemes. wherein R 1 , R 2 , R 3 and R 4 are each as defined above;
- -A 1 - is -CH 2 -;
- Suitable salts and pharmaceutically acceptable salts of the starting and object compounds are conventional non-toxic salt and include an acid addition salt such as an organic acid salt (e.g. acetate, trifluoroacetate, fumarate, maleate, tartrate, methanesulfonate, benzenesulfonate, formate, toluenesulfonate, etc.), an inorganic acid salt (e.g.
- hydrochloride hydrobromide, hydroiodide, sulfate, nitrate, phosphate, etc.
- a salt with an amino acid e.g.
- arginine aspartic acid, glutamic acid, etc.
- a metal salt such as an alkali metal salt (e.g. sodium salt,
- potassium salt, etc. and an alkaline earth metal salt (e.g. calcium salt, magnesium salt, etc.), an ammonium salt, an organic base salt (e.g. trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.), or the like.
- alkaline earth metal salt e.g. calcium salt, magnesium salt, etc.
- an ammonium salt e.g. calcium salt, magnesium salt, etc.
- an organic base salt e.g. trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.
- Suitable "lower alkyl” and “lower alkyl moiety" in the terms “indolyl (lower) alkyl” and “lower alkylsulfonyl” is straight or branched one having 1 to 6 carbon atom(s) and may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl and the like.
- Suitable “trihalo (lower) alkyl” may include
- alkoxy (lower) alkanoyl may include methoxy, ethoxy,
- Suitable "lower alkanoyl” and “lower alkanoyl moiety" in the term “lower alkoxy (lower) alkanoyl” may include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, hexanoyl, pivaloyl and the like.
- cyclo (lower) alkylcarbonyl may include cyclopropyl
- Suitable “aroyl” may include benzoyl, toluoyl, naphthoyl and the like.
- Suitable “leaving group” may include hydroxy, reactive group derived from hydroxy and the like.
- Suitable "reactive group derived from hydroxy” may include acid residue and the like.
- Suitable "acid residue” may include halogen (e.g.
- Process 1 for preparing the object compounds of the present invention are explained in detail in the following.
- the object compound (I) or a salt thereof can be
- Suitable reactive derivative at the carboxy group of the compound (II) may include an acid halide, an acid anhydride, an activated amide, an activated ester, and the like.
- Suitable examples of the reactive derivatives may be an acid chloride; an acid azide; a mixed acid anhydride with an acid such as substituted phosphoric acid [e.g.
- diphenylphosphoric acid dibenzylphosphoric acid, halogenated phosphoric acid, etc.
- dialkylphosphorous acid sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acid [e.g. methanesulfonic acid, etc.], aliphatic carboxylic acid [e.g. acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, pentanoic acid, isopentanoic acid,
- Suitable reactive derivative at the amino group of the compound (III) may include Schiff's base type imino or its tautomeric enamine type isomer formed by the reaction of the compound (III) with a carbonyl compound such as aldehyde, ketone or the like; a silyl derivative formed by the reaction of the compound (III) with a silyl compound such as
- the reaction is usually carried out in a conventional solvent such as water, alcohol [e.g. methanol, ethanol, etc.], acetone, 2-butanone, dioxane, acetonitrile,
- a conventional solvent such as water, alcohol [e.g. methanol, ethanol, etc.], acetone, 2-butanone, dioxane, acetonitrile,
- reaction when the compound (II) is used in a free acid form or its salt form, the reaction is preferably carried out in the presence of a conventional condensing agent such as N,N' -dicyclohexylcarbodiimide;
- N,N'-diethylcarbodiimide N,N'-diisopropylcarbodiimide
- phosphorus oxychloride (phosphoryl chloride); phosphorus trichloride; diphenyl phosphorylazide; thionyl chloride;
- triphenylphosphine 2-ethyl-7-hydroxybenzisoxazolium salt; 2-ethyl-5-(m-sulfophenyl)isoxazolium hydroxide intramolecular salt; 1-(p-chlorobenzenesulfonyloxy)-6-chloro-1H- benzotriazole; 1-hydroxybenzotriazole; so-called Mukaiyama reagent such as 2-chloro-1-methylpyridinium iodide;
- the reaction may also be carried out in the presence of an inorganic or organic base such as an alkali metal
- N-(lower)alkylmorpholine N,N-di(lower)alkylbenzylamine, or the like.
- the reaction temperature is not critical, and the reaction is usually carried out under cooling to warming.
- the object compound (If) can be prepared by reacting the compound (I) or a salt thereof other than fumaric acid salt thereof with fumaric acid.
- the reaction is usually carried out in a conventional solvent such as water, alcohol [e.g. methanol, ethanol, etc.], acetone, 2-butanone, dioxane, acetonitrile,
- a conventional solvent such as water, alcohol [e.g. methanol, ethanol, etc.], acetone, 2-butanone, dioxane, acetonitrile,
- the reaction temperature is not critical, and the reaction is usually carried out under cooling to warming.
- the object compound (Ig') or a salt thereof can be prepared by reacting the compound (IV) or its reactive derivative at the imino group or a salt thereof with the compound (V) or a salt thereof.
- Suitable reactive derivative at the imino group of the compound (IV) may include Schiff's base type imino or its tautomeric enamine type isomer formed by the reaction of the compound (IV) with a carbonyl compound such as aldehyde, ketone or the like; a silyl derivative formed by the reaction of the compound (IV) with a silyl compound such as
- This reaction is usually carried out in a solvent such as alcohol [e.g. methanol, ethanol, etc.], dichloromethane, benzene, N,N-dimethylformamide, tetrahydrofuran, diethyl ether or any other solvent which does not adversely affect the reaction.
- a solvent such as alcohol [e.g. methanol, ethanol, etc.], dichloromethane, benzene, N,N-dimethylformamide, tetrahydrofuran, diethyl ether or any other solvent which does not adversely affect the reaction.
- the raction may be carried out in the presence of an inorganic or an organic base such as an alkali metal
- hydroxide e.g. sodium hydroxide, potassium hydroxide, etc.
- an alkali metal carbonate e.g. sodium carbonate, potassium carbonate, etc.
- an alkali metal bicarbonate e.g. sodium bicarbonate, potassium bicarbonate, etc.
- alkali metal hydride e.g. sodium hydride, potassium hydride, etc.
- tri (lower) alkylamine e.g. trimethylamine, triethylamine, diisopropylethylamine, etc.]
- the base to be used in liquid it can also be used as a solvent.
- the reaction temperature is not critical, and the reaction can be carried out under cooling, at room
- the compound (Ig") or a salt thereof can be prepared by reacting a compound (IV) or its reactive derivative at the imino group or a salt thereof with a compound (VI) or its reactive derivative at the carboxy group or a salt thereof.
- the reaction can be carried out in the manner disclosed in Preparation 10 or similar manners thereto.
- the object compounds of the present invention have pharmacological activities such as Tachykinin antagonism, especially Substance P antagonism, Neurokinin A antagonism or Neurokinin B antagonism, and therefore are useful for treating or preventing Tachykinin-mediated diseases,
- Substance P-mediated diseases for example, respiratory diseases such as asthma, bronchitis (e.g. chronic bronchitis, acute bronchitis and diffuse panbronchiolitis, etc.), rhinitis, cough, expectoration, and the like;
- respiratory diseases such as asthma, bronchitis (e.g. chronic bronchitis, acute bronchitis and diffuse panbronchiolitis, etc.), rhinitis, cough, expectoration, and the like;
- ophthalmic diseases such as conjunctivitis, vernal
- cutaneous diseases such as contact dermatitis, atopic
- dermatitis dermatitis, urticaria, and other eczematoid dermatitis, and the like; inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and the like;
- pains or aches e.g. migraine, headache, cluster headache, toothache, cancerous pain, back pain, neuralgia, etc.; and the like.
- the object compounds of the present invention are useful for treating or preventing ophthalmic diseases such as glaucoma, uveitis, and the like; gastrointestinal diseases such as ulcer, ulcerative colitis, irritable bowel syndrome, food allergy, and the like;
- inflammatory diseases such as nephritis, and the like, circulatory diseases such as hypertension, angina pectoris, cardiac failure, thrombosis, Raynaud's disease, and the like; epilepsy; spastic paralysis; pollakiuria; cystitis; bladder detrusor hyperreflexia; urinary incontinence; Parkinson- diseases; dementia; AIDS related dementia; Alzheimer's diseases; Down's syndrome; Huntington's chorea; carcinoid syndrome; disorders related to immune enhancement or
- the object compounds of the present invention are useful for treating or preventing chronic obstructive pulmonary diseases, particularly chronic pulmonary emphysema; blinkis; proliferative vitreoretinopathy; psoriasis; inflammatory intestinal diseases, particularly Crohn's diseases; hepatitis; superficial pain on congelation, burn, herpes zoster or diabetic neuropathy; tenalgia attended to hyperlipidemia; postoperative neuroma, particularly of mastectomy; vulvar vestibulitis; hemodialysis-associated itching; lichen planus; laryngopharyngitis; bronchiectasis; coniosis; whooping cough; pulmonary tuberculosis; cystic fibrosis; emesis; mental diseases, particularly anxiety, depression, dysthymic disorders and schizophrenia;
- demyelinating diseases such as multiple sclerosis and
- amyotrophic lateral sclerosis amyotrophic lateral sclerosis; attenuation of morphine withdrawal; oedema, such as oedema caused by thermal injury; small cell carcinomas, particularly small cell lung cancer (SCLC); hypersensitivity disorders such as poison ivy;
- fibrosing and collagen diseases such as scleroderma and eosinophilic fascioliasis; reflex sympathetic dystrophy such as shoulder/hand syndrome; addiction disorders such as alcoholism; stress related somatic disorders; rheumatic diseases such as fibrositis; and the like.
- the object compounds of the present invention can be used in a form of pharmaceutical preparation containing one of said compound, as an active ingredient, in admixture with a pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient suitable for oral, parenteral, external including topical, enteral, intravenous, intramuscular, inhalant, nasal, intraarticular, intraspinal, transtracheal or
- a pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient suitable for oral, parenteral, external including topical, enteral, intravenous, intramuscular, inhalant, nasal, intraarticular, intraspinal, transtracheal or
- the pharmaceutical preparations may be solid, semi-solid or solutions such as capsules, tablets, pellets, dragees, powders, granules, suppositories, ointments, creams, lotions, inhalants, injections,
- aerosols suspension, emulsion, or the like. If desired, there may be included in these preparations, auxiliary substances, stabilizing agents, wetting or emulsifying agents, buffers and other commonly used additives.
- an average single dose of about 0.1 mg, 1 mg, 10 mg, 50 mg, 100 mg, 250 mg, 500 mg and 1000 mg of the object compounds may be
- kits for treating Tachykinin-mediated diseases such as asthma and the like.
- amounts between 0.1 mg/body and about 1,000 mg/body may be administered per day.
- Example 2 1 25 I-BH-Substance P Binding to h-NK 1 Receptors Test Method : 125 I-BH-Substance P Binding to h-NK 1 Receptors
- CHO cells permanently expressing h-NK-, receptors were harvested and homogenized with a Dounce homogenizer at 4°C in a buffer (0.25 M sucrose, 25 mM Tris-HCl pH 7.4, 10 mM MgCl 2 ,
- buffer 25 mM Tris-HCl pH 7.4, 10 mM MgCl 2 , 1 mM EDTA, 5 ⁇ g/ml p-APMSF
- buffer 25 mM Tris-HCl pH 7.4, 10 mM MgCl 2 , 1 mM EDTA, 5 ⁇ g/ml p-APMSF
- the object compound of the present invention is also superior in stability and the like.
- IR (CCCl 3 ) 3430, 3300, 3000, 2910, 2800,
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU57031/96A AU706021B2 (en) | 1995-05-25 | 1996-05-21 | Piperazine derivatives |
MX9709079A MX9709079A (en) | 1996-05-21 | 1996-05-21 | 1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists. |
EA199700425A EA000669B1 (en) | 1995-05-25 | 1996-05-21 | Piperazine derivatives |
EP96915200A EP0846116A1 (en) | 1995-05-25 | 1996-05-21 | 1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists |
NZ307625A NZ307625A (en) | 1995-05-25 | 1996-05-21 | 1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists |
JP8535553A JP3071829B2 (en) | 1995-05-25 | 1996-05-21 | 1-benzoyl-2- (indolyl-3-alkyl) -piperazine derivatives as neurokinin receptor antagonists |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US45017695A | 1995-05-25 | 1995-05-25 | |
US08/450,176 | 1995-05-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996037489A1 true WO1996037489A1 (en) | 1996-11-28 |
Family
ID=23787083
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1996/001335 WO1996037489A1 (en) | 1995-05-25 | 1996-05-21 | 1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists |
Country Status (14)
Country | Link |
---|---|
EP (1) | EP0846116A1 (en) |
JP (1) | JP3071829B2 (en) |
KR (1) | KR19990021857A (en) |
CN (1) | CN1072220C (en) |
AU (1) | AU706021B2 (en) |
CA (1) | CA2222041A1 (en) |
EA (1) | EA000669B1 (en) |
HU (1) | HUP9900822A3 (en) |
IL (1) | IL118369A (en) |
NZ (1) | NZ307625A (en) |
TR (1) | TR199600438A2 (en) |
TW (1) | TW391960B (en) |
WO (1) | WO1996037489A1 (en) |
ZA (1) | ZA964101B (en) |
Cited By (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0773026A2 (en) * | 1995-11-06 | 1997-05-14 | Pfizer Inc. | NK-1 receptor antagonists for the treatment of cancer |
WO1997022597A1 (en) * | 1995-12-18 | 1997-06-26 | Fujisawa Pharmaceutical Co., Ltd. | Piperazine derivatives as tachykinin antagonists |
WO1998057954A1 (en) * | 1997-06-17 | 1998-12-23 | Fujisawa Pharmaceutical Co., Ltd. | Aroyl-piperazine derivatives, their preparation and their use as tachykinin antagonists |
EP0899270A1 (en) * | 1997-08-27 | 1999-03-03 | Solvay Pharmaceuticals GmbH | Indolylmethyl-N,N'-bisacylpiperazines as neurokinine receptor antagonists |
US6001833A (en) * | 1997-08-27 | 1999-12-14 | Solvay Pharmaceuticals Gmbh | Urea derivatives |
WO2003006459A1 (en) * | 2001-07-09 | 2003-01-23 | Solvay Pharmaceuticals B.V. | Piperazine oxime derivatives having nk-1 receptor antagonistic activity |
WO2003084955A1 (en) | 2002-04-04 | 2003-10-16 | Solvay Pharmaceuticals B.V. | Diazabicyclo alkane derivatives with nk1 antagonistic activity |
US6833373B1 (en) | 1998-12-23 | 2004-12-21 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
WO2006123182A2 (en) | 2005-05-17 | 2006-11-23 | Merck Sharp & Dohme Limited | Cyclohexyl sulphones for treatment of cancer |
WO2007011820A2 (en) | 2005-07-15 | 2007-01-25 | Amr Technology, Inc. | Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
WO2007041052A2 (en) | 2005-09-29 | 2007-04-12 | Merck & Co., Inc. | Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators |
WO2007093827A1 (en) | 2006-02-15 | 2007-08-23 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Thiophene and thiazole substituted trifluoroethanone derivatives as histone deacetylase (hdac) inhibitors |
WO2008090117A1 (en) | 2007-01-24 | 2008-07-31 | Glaxo Group Limited | Pharmaceutical compositions comprising 3, 5-diamin0-6- (2, 3-dichl0phenyl) -l, 2, 4-triazine or r (-) -2, 4-diamino-5- (2, 3-dichlorophenyl) -6-fluoromethyl pyrimidine and an nk1 |
WO2008120653A1 (en) | 2007-04-02 | 2008-10-09 | Banyu Pharmaceutical Co., Ltd. | Indoledione derivative |
WO2008147864A2 (en) * | 2007-05-22 | 2008-12-04 | Xenon Pharmaceuticals Inc. | Methods of using piperazine compounds in treating sodium channel-mediated diseases or conditions |
WO2009002495A1 (en) | 2007-06-27 | 2008-12-31 | Merck & Co., Inc. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
WO2009111354A2 (en) | 2008-03-03 | 2009-09-11 | Tiger Pharmatech | Tyrosine kinase inhibitors |
WO2010114780A1 (en) | 2009-04-01 | 2010-10-07 | Merck Sharp & Dohme Corp. | Inhibitors of akt activity |
WO2010132487A1 (en) | 2009-05-12 | 2010-11-18 | Bristol-Myers Squibb Company | CRYSTALLINE FORMS OF (S)-7-([1,2,4]TRIAZOLO[1,5-a]PYRIDIN-6-YL)-4-(3,4-DICHLOROHPHENYL)-1,2,3,4-TETRAHYDROISOQUINOLINE AND USE THEREOF |
WO2010132442A1 (en) | 2009-05-12 | 2010-11-18 | Albany Molecular Reserch, Inc. | 7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof |
WO2011046771A1 (en) | 2009-10-14 | 2011-04-21 | Schering Corporation | SUBSTITUTED PIPERIDINES THAT INCREASE p53 ACTIVITY AND THE USES THEREOF |
EP2336120A1 (en) | 2007-01-10 | 2011-06-22 | Istituto di ricerche di Biologia Molecolare P. Angeletti S.R.L. | Combinations containing amide substituted indazoles as poly(ADP-ribose)polymerase (PARP) inhibitors |
WO2011163330A1 (en) | 2010-06-24 | 2011-12-29 | Merck Sharp & Dohme Corp. | Novel heterocyclic compounds as erk inhibitors |
WO2012018754A2 (en) | 2010-08-02 | 2012-02-09 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF CATENIN (CADHERIN-ASSOCIATED PROTEIN), BETA 1 (CTNNB1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
WO2012027236A1 (en) | 2010-08-23 | 2012-03-01 | Schering Corporation | NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
WO2012030685A2 (en) | 2010-09-01 | 2012-03-08 | Schering Corporation | Indazole derivatives useful as erk inhibitors |
WO2012036997A1 (en) | 2010-09-16 | 2012-03-22 | Schering Corporation | Fused pyrazole derivatives as novel erk inhibitors |
WO2012087772A1 (en) | 2010-12-21 | 2012-06-28 | Schering Corporation | Indazole derivatives useful as erk inhibitors |
WO2012145471A1 (en) | 2011-04-21 | 2012-10-26 | Merck Sharp & Dohme Corp. | Insulin-like growth factor-1 receptor inhibitors |
WO2013063214A1 (en) | 2011-10-27 | 2013-05-02 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
WO2013165816A2 (en) | 2012-05-02 | 2013-11-07 | Merck Sharp & Dohme Corp. | SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS |
EP2698157A1 (en) | 2006-09-22 | 2014-02-19 | Merck Sharp & Dohme Corp. | Method of treatment using fatty acid synthesis inhibitors |
WO2014052563A2 (en) | 2012-09-28 | 2014-04-03 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
WO2014085216A1 (en) | 2012-11-28 | 2014-06-05 | Merck Sharp & Dohme Corp. | Compositions and methods for treating cancer |
WO2014100065A1 (en) | 2012-12-20 | 2014-06-26 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as hdm2 inhibitors |
WO2014120748A1 (en) | 2013-01-30 | 2014-08-07 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as hdm2 inhibitors |
WO2015034925A1 (en) | 2013-09-03 | 2015-03-12 | Moderna Therapeutics, Inc. | Circular polynucleotides |
US9034899B2 (en) | 2009-05-12 | 2015-05-19 | Albany Molecular Research, Inc. | Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof |
US9085531B2 (en) | 2004-07-15 | 2015-07-21 | Albany Molecular Research, Inc. | Aryl- and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
EP3327125A1 (en) | 2010-10-29 | 2018-05-30 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
WO2019094311A1 (en) | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
WO2020033284A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
WO2020033282A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
US11096950B2 (en) | 2006-11-01 | 2021-08-24 | Barbara Brooke Jennings | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
EP4079856A1 (en) | 2010-08-17 | 2022-10-26 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10036818A1 (en) * | 2000-07-28 | 2002-02-07 | Solvay Pharm Gmbh | New N-Triazolylmethyl-Piperazine Derivatives as Neurokinin Receptor Antagonists |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0411150A1 (en) * | 1989-02-10 | 1991-02-06 | Otsuka Pharmaceutical Co., Ltd. | Indole derivatives, preparation thereof, and drug for preventing and treating nephritis containing same |
EP0655442A1 (en) * | 1993-11-29 | 1995-05-31 | Fujisawa Pharmaceutical Co., Ltd. | Piperazine derivatives as Tachykinin antagonists |
-
1996
- 1996-05-21 JP JP8535553A patent/JP3071829B2/en not_active Expired - Fee Related
- 1996-05-21 EP EP96915200A patent/EP0846116A1/en not_active Ceased
- 1996-05-21 EA EA199700425A patent/EA000669B1/en not_active IP Right Cessation
- 1996-05-21 KR KR1019970708331A patent/KR19990021857A/en not_active Application Discontinuation
- 1996-05-21 HU HU9900822A patent/HUP9900822A3/en unknown
- 1996-05-21 CA CA002222041A patent/CA2222041A1/en not_active Abandoned
- 1996-05-21 AU AU57031/96A patent/AU706021B2/en not_active Ceased
- 1996-05-21 WO PCT/JP1996/001335 patent/WO1996037489A1/en not_active Application Discontinuation
- 1996-05-21 CN CN96195744A patent/CN1072220C/en not_active Expired - Fee Related
- 1996-05-21 NZ NZ307625A patent/NZ307625A/en unknown
- 1996-05-22 ZA ZA964101A patent/ZA964101B/en unknown
- 1996-05-22 IL IL11836996A patent/IL118369A/en active IP Right Grant
- 1996-05-23 TW TW085106105A patent/TW391960B/en not_active IP Right Cessation
- 1996-05-24 TR TR96/00438A patent/TR199600438A2/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0411150A1 (en) * | 1989-02-10 | 1991-02-06 | Otsuka Pharmaceutical Co., Ltd. | Indole derivatives, preparation thereof, and drug for preventing and treating nephritis containing same |
EP0655442A1 (en) * | 1993-11-29 | 1995-05-31 | Fujisawa Pharmaceutical Co., Ltd. | Piperazine derivatives as Tachykinin antagonists |
Cited By (64)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0773026A3 (en) * | 1995-11-06 | 1999-11-17 | Pfizer Inc. | NK-1 receptor antagonists for the treatment of cancer |
EP0773026A2 (en) * | 1995-11-06 | 1997-05-14 | Pfizer Inc. | NK-1 receptor antagonists for the treatment of cancer |
WO1997022597A1 (en) * | 1995-12-18 | 1997-06-26 | Fujisawa Pharmaceutical Co., Ltd. | Piperazine derivatives as tachykinin antagonists |
WO1998057954A1 (en) * | 1997-06-17 | 1998-12-23 | Fujisawa Pharmaceutical Co., Ltd. | Aroyl-piperazine derivatives, their preparation and their use as tachykinin antagonists |
US6924278B2 (en) | 1997-06-17 | 2005-08-02 | Fujisawa Pharmaceutical Co., Ltd. | Aroyl-piperazine derivatives, their preparation and their use as tachykinin antagonists |
EP0899270A1 (en) * | 1997-08-27 | 1999-03-03 | Solvay Pharmaceuticals GmbH | Indolylmethyl-N,N'-bisacylpiperazines as neurokinine receptor antagonists |
US6001833A (en) * | 1997-08-27 | 1999-12-14 | Solvay Pharmaceuticals Gmbh | Urea derivatives |
CN1108290C (en) * | 1997-08-27 | 2003-05-14 | 索尔瓦药物有限公司 | Urea derivatives |
US6833373B1 (en) | 1998-12-23 | 2004-12-21 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
AU2002333229B2 (en) * | 2001-07-09 | 2006-11-30 | Solvay Pharmaceuticals B.V. | Piperazine oxime derivatives having NK-1 receptor antagonistic activity |
WO2003006459A1 (en) * | 2001-07-09 | 2003-01-23 | Solvay Pharmaceuticals B.V. | Piperazine oxime derivatives having nk-1 receptor antagonistic activity |
US7094779B2 (en) | 2001-07-09 | 2006-08-22 | Solvay Pharmaceuticals B.V. | Piperazine oxime dervatives having NK-1 receptor antagonistic activity |
WO2003084955A1 (en) | 2002-04-04 | 2003-10-16 | Solvay Pharmaceuticals B.V. | Diazabicyclo alkane derivatives with nk1 antagonistic activity |
US7202238B2 (en) | 2002-04-04 | 2007-04-10 | Solvay Pharmaceuticals B.V. | Diazabicyclo alkane derivatives with NK1 antagonistic activity |
US9085531B2 (en) | 2004-07-15 | 2015-07-21 | Albany Molecular Research, Inc. | Aryl- and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
US9499531B2 (en) | 2004-07-15 | 2016-11-22 | Albany Molecular Research, Inc. | Aryl- and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
WO2006123182A2 (en) | 2005-05-17 | 2006-11-23 | Merck Sharp & Dohme Limited | Cyclohexyl sulphones for treatment of cancer |
WO2007011820A2 (en) | 2005-07-15 | 2007-01-25 | Amr Technology, Inc. | Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
US9403776B2 (en) | 2005-07-15 | 2016-08-02 | Albany Molecular Research, Inc. | Aryl- and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
WO2007041052A2 (en) | 2005-09-29 | 2007-04-12 | Merck & Co., Inc. | Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators |
WO2007093827A1 (en) | 2006-02-15 | 2007-08-23 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Thiophene and thiazole substituted trifluoroethanone derivatives as histone deacetylase (hdac) inhibitors |
EP2698157A1 (en) | 2006-09-22 | 2014-02-19 | Merck Sharp & Dohme Corp. | Method of treatment using fatty acid synthesis inhibitors |
EP2946778A1 (en) | 2006-09-22 | 2015-11-25 | Merck Sharp & Dohme Corp. | Method of treatment using fatty acid synthesis inhibitors |
US11096950B2 (en) | 2006-11-01 | 2021-08-24 | Barbara Brooke Jennings | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
EP2805945A1 (en) | 2007-01-10 | 2014-11-26 | MSD Italia S.r.l. | Amide substituted indazoles as poly(ADP-ribose)polymerase (PARP) inhibitors |
EP2336120A1 (en) | 2007-01-10 | 2011-06-22 | Istituto di ricerche di Biologia Molecolare P. Angeletti S.R.L. | Combinations containing amide substituted indazoles as poly(ADP-ribose)polymerase (PARP) inhibitors |
WO2008090117A1 (en) | 2007-01-24 | 2008-07-31 | Glaxo Group Limited | Pharmaceutical compositions comprising 3, 5-diamin0-6- (2, 3-dichl0phenyl) -l, 2, 4-triazine or r (-) -2, 4-diamino-5- (2, 3-dichlorophenyl) -6-fluoromethyl pyrimidine and an nk1 |
WO2008120653A1 (en) | 2007-04-02 | 2008-10-09 | Banyu Pharmaceutical Co., Ltd. | Indoledione derivative |
WO2008147864A2 (en) * | 2007-05-22 | 2008-12-04 | Xenon Pharmaceuticals Inc. | Methods of using piperazine compounds in treating sodium channel-mediated diseases or conditions |
WO2008147864A3 (en) * | 2007-05-22 | 2009-07-09 | Xenon Pharmaceuticals Inc | Methods of using piperazine compounds in treating sodium channel-mediated diseases or conditions |
EP3103791A1 (en) | 2007-06-27 | 2016-12-14 | Merck Sharp & Dohme Corp. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
WO2009002495A1 (en) | 2007-06-27 | 2008-12-31 | Merck & Co., Inc. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
WO2009111354A2 (en) | 2008-03-03 | 2009-09-11 | Tiger Pharmatech | Tyrosine kinase inhibitors |
US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
US9498476B2 (en) | 2008-06-04 | 2016-11-22 | Albany Molecular Research, Inc. | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
WO2010114780A1 (en) | 2009-04-01 | 2010-10-07 | Merck Sharp & Dohme Corp. | Inhibitors of akt activity |
US9173879B2 (en) | 2009-05-12 | 2015-11-03 | Bristol-Myers Squibb Company | Crystalline forms of (S)-7-([1,2,4]triazolo[1,5-a ]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline and use thereof |
US9034899B2 (en) | 2009-05-12 | 2015-05-19 | Albany Molecular Research, Inc. | Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof |
US9604960B2 (en) | 2009-05-12 | 2017-03-28 | Albany Molecular Research, Inc. | Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof |
WO2010132487A1 (en) | 2009-05-12 | 2010-11-18 | Bristol-Myers Squibb Company | CRYSTALLINE FORMS OF (S)-7-([1,2,4]TRIAZOLO[1,5-a]PYRIDIN-6-YL)-4-(3,4-DICHLOROHPHENYL)-1,2,3,4-TETRAHYDROISOQUINOLINE AND USE THEREOF |
WO2010132442A1 (en) | 2009-05-12 | 2010-11-18 | Albany Molecular Reserch, Inc. | 7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof |
WO2011046771A1 (en) | 2009-10-14 | 2011-04-21 | Schering Corporation | SUBSTITUTED PIPERIDINES THAT INCREASE p53 ACTIVITY AND THE USES THEREOF |
WO2011163330A1 (en) | 2010-06-24 | 2011-12-29 | Merck Sharp & Dohme Corp. | Novel heterocyclic compounds as erk inhibitors |
EP3330377A1 (en) | 2010-08-02 | 2018-06-06 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (ctnnb1) gene expression using short interfering nucleic acid (sina) |
WO2012018754A2 (en) | 2010-08-02 | 2012-02-09 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF CATENIN (CADHERIN-ASSOCIATED PROTEIN), BETA 1 (CTNNB1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
EP4079856A1 (en) | 2010-08-17 | 2022-10-26 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina) |
WO2012027236A1 (en) | 2010-08-23 | 2012-03-01 | Schering Corporation | NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
WO2012030685A2 (en) | 2010-09-01 | 2012-03-08 | Schering Corporation | Indazole derivatives useful as erk inhibitors |
WO2012036997A1 (en) | 2010-09-16 | 2012-03-22 | Schering Corporation | Fused pyrazole derivatives as novel erk inhibitors |
EP3327125A1 (en) | 2010-10-29 | 2018-05-30 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
EP3766975A1 (en) | 2010-10-29 | 2021-01-20 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acid (sina) |
WO2012087772A1 (en) | 2010-12-21 | 2012-06-28 | Schering Corporation | Indazole derivatives useful as erk inhibitors |
WO2012145471A1 (en) | 2011-04-21 | 2012-10-26 | Merck Sharp & Dohme Corp. | Insulin-like growth factor-1 receptor inhibitors |
WO2013063214A1 (en) | 2011-10-27 | 2013-05-02 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
EP3919620A1 (en) | 2012-05-02 | 2021-12-08 | Sirna Therapeutics, Inc. | Short interfering nucleic acid (sina) compositions |
WO2013165816A2 (en) | 2012-05-02 | 2013-11-07 | Merck Sharp & Dohme Corp. | SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS |
WO2014052563A2 (en) | 2012-09-28 | 2014-04-03 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
WO2014085216A1 (en) | 2012-11-28 | 2014-06-05 | Merck Sharp & Dohme Corp. | Compositions and methods for treating cancer |
WO2014100065A1 (en) | 2012-12-20 | 2014-06-26 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as hdm2 inhibitors |
WO2014120748A1 (en) | 2013-01-30 | 2014-08-07 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as hdm2 inhibitors |
WO2015034925A1 (en) | 2013-09-03 | 2015-03-12 | Moderna Therapeutics, Inc. | Circular polynucleotides |
WO2019094311A1 (en) | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
WO2020033284A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
WO2020033282A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
Also Published As
Publication number | Publication date |
---|---|
IL118369A0 (en) | 1996-09-12 |
JPH11505830A (en) | 1999-05-25 |
NZ307625A (en) | 1999-02-25 |
HUP9900822A2 (en) | 1999-06-28 |
AU5703196A (en) | 1996-12-11 |
HUP9900822A3 (en) | 1999-11-29 |
IL118369A (en) | 2000-06-01 |
ZA964101B (en) | 1996-07-29 |
TW391960B (en) | 2000-06-01 |
AU706021B2 (en) | 1999-06-03 |
EA199700425A1 (en) | 1998-12-24 |
TR199600438A2 (en) | 1996-12-21 |
CN1072220C (en) | 2001-10-03 |
EP0846116A1 (en) | 1998-06-10 |
CA2222041A1 (en) | 1996-11-28 |
KR19990021857A (en) | 1999-03-25 |
CN1191533A (en) | 1998-08-26 |
EA000669B1 (en) | 2000-02-28 |
JP3071829B2 (en) | 2000-07-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO1996037489A1 (en) | 1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists | |
EP0655442B1 (en) | Piperazine derivatives as Tachykinin antagonists | |
US6087357A (en) | Piperazine derivatives as tachykinin antagonists | |
RU2258702C2 (en) | Derivatives of aroylpiperazine, method for their preparing, pharmaceutical composition based on thereof and method for treatment | |
EP0640099B1 (en) | Peptides having tachykinin antagonist activity | |
CA2033363A1 (en) | Quinazoline derivatives and their preparation | |
US5939413A (en) | Piperazine derivatives | |
US5883098A (en) | Piperazine derivatives | |
US5654400A (en) | Process for making peptide compounds having tachykinin antagonistic activity | |
MXPA97009079A (en) | Derivatives of 1-benzol-2- (indolil-3-alkyl) piperazine as antagonists of the neuroquin receiver | |
AU743723B2 (en) | Aroyl-piperazine derivatives, their preparation and their use as tachykinin antagonists | |
MXPA98004887A (en) | Piperazine derivatives as taquicin antagonists | |
MXPA99011778A (en) | Aroyl-piperazine derivatives, their preparation and their use as tachykinin antagonists |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 96195744.1 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA CN HU JP KR MX NZ AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref document number: 1996 535553 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1019970708331 Country of ref document: KR |
|
ENP | Entry into the national phase |
Ref document number: 2222041 Country of ref document: CA Ref document number: 2222041 Country of ref document: CA Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/1997/009079 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1996915200 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 307625 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 199700425 Country of ref document: EA |
|
WWP | Wipo information: published in national office |
Ref document number: 1996915200 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1019970708331 Country of ref document: KR |
|
WWR | Wipo information: refused in national office |
Ref document number: 1996915200 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1996915200 Country of ref document: EP |
|
WWR | Wipo information: refused in national office |
Ref document number: 1019970708331 Country of ref document: KR |