RU2018138195A - Соединения 3,5-диамино-6-хлор-n-(n-(4- фенилбутил)карбамимидоил)пиразин-2-карбоксамида - Google Patents
Соединения 3,5-диамино-6-хлор-n-(n-(4- фенилбутил)карбамимидоил)пиразин-2-карбоксамида Download PDFInfo
- Publication number
- RU2018138195A RU2018138195A RU2018138195A RU2018138195A RU2018138195A RU 2018138195 A RU2018138195 A RU 2018138195A RU 2018138195 A RU2018138195 A RU 2018138195A RU 2018138195 A RU2018138195 A RU 2018138195A RU 2018138195 A RU2018138195 A RU 2018138195A
- Authority
- RU
- Russia
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- compound according
- treatment
- dry
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims 24
- 150000003839 salts Chemical class 0.000 claims 23
- 125000000217 alkyl group Chemical group 0.000 claims 11
- 201000003883 Cystic fibrosis Diseases 0.000 claims 9
- 238000000034 method Methods 0.000 claims 9
- 206010035664 Pneumonia Diseases 0.000 claims 8
- 201000009267 bronchiectasis Diseases 0.000 claims 8
- 206010006451 bronchitis Diseases 0.000 claims 8
- 230000018044 dehydration Effects 0.000 claims 8
- 238000006297 dehydration reaction Methods 0.000 claims 8
- 206010013781 dry mouth Diseases 0.000 claims 8
- 201000009890 sinusitis Diseases 0.000 claims 8
- 239000000203 mixture Substances 0.000 claims 7
- 210000002850 nasal mucosa Anatomy 0.000 claims 7
- 241000282412 Homo Species 0.000 claims 6
- 125000004432 carbon atom Chemical group C* 0.000 claims 6
- 206010061876 Obstruction Diseases 0.000 claims 5
- 201000010099 disease Diseases 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 5
- 230000036571 hydration Effects 0.000 claims 5
- 238000006703 hydration reaction Methods 0.000 claims 5
- 230000002265 prevention Effects 0.000 claims 5
- 210000002345 respiratory system Anatomy 0.000 claims 5
- 206010006448 Bronchiolitis Diseases 0.000 claims 4
- 206010006458 Bronchitis chronic Diseases 0.000 claims 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 4
- 208000025678 Ciliary Motility disease Diseases 0.000 claims 4
- 206010010774 Constipation Diseases 0.000 claims 4
- 206010011224 Cough Diseases 0.000 claims 4
- 208000005156 Dehydration Diseases 0.000 claims 4
- 206010056361 Distal intestinal obstruction syndrome Diseases 0.000 claims 4
- 206010013786 Dry skin Diseases 0.000 claims 4
- 206010014561 Emphysema Diseases 0.000 claims 4
- 206010030216 Oesophagitis Diseases 0.000 claims 4
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 4
- 206010044314 Tracheobronchitis Diseases 0.000 claims 4
- 208000009470 Ventilator-Associated Pneumonia Diseases 0.000 claims 4
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims 4
- 208000005946 Xerostomia Diseases 0.000 claims 4
- 208000006673 asthma Diseases 0.000 claims 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 4
- 210000005252 bulbus oculi Anatomy 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 208000007451 chronic bronchitis Diseases 0.000 claims 4
- 210000004087 cornea Anatomy 0.000 claims 4
- 208000007784 diverticulitis Diseases 0.000 claims 4
- 230000037336 dry skin Effects 0.000 claims 4
- 208000006881 esophagitis Diseases 0.000 claims 4
- 230000002427 irreversible effect Effects 0.000 claims 4
- 206010023332 keratitis Diseases 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 239000001301 oxygen Substances 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 201000009266 primary ciliary dyskinesia Diseases 0.000 claims 4
- 230000002441 reversible effect Effects 0.000 claims 4
- 230000000638 stimulation Effects 0.000 claims 4
- 238000002054 transplantation Methods 0.000 claims 4
- 206010033078 Otitis media Diseases 0.000 claims 3
- 230000001684 chronic effect Effects 0.000 claims 3
- 208000003243 intestinal obstruction Diseases 0.000 claims 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 2
- 108010078678 Osmolite Proteins 0.000 claims 2
- 239000000443 aerosol Substances 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 claims 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims 1
- 229930195725 Mannitol Natural products 0.000 claims 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims 1
- 102000001744 Purinergic P2Y2 Receptors Human genes 0.000 claims 1
- 108010029812 Purinergic P2Y2 Receptors Proteins 0.000 claims 1
- 108010052164 Sodium Channels Proteins 0.000 claims 1
- 102000018674 Sodium Channels Human genes 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 229940124599 anti-inflammatory drug Drugs 0.000 claims 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 claims 1
- 229940125715 antihistaminic agent Drugs 0.000 claims 1
- 239000000739 antihistaminic agent Substances 0.000 claims 1
- 229960005475 antiinfective agent Drugs 0.000 claims 1
- 239000004599 antimicrobial Substances 0.000 claims 1
- 229940125388 beta agonist Drugs 0.000 claims 1
- 230000000903 blocking effect Effects 0.000 claims 1
- 239000000812 cholinergic antagonist Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940112141 dry powder inhaler Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 230000000968 intestinal effect Effects 0.000 claims 1
- 229940043355 kinase inhibitor Drugs 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 235000010355 mannitol Nutrition 0.000 claims 1
- 239000000594 mannitol Substances 0.000 claims 1
- 210000004379 membrane Anatomy 0.000 claims 1
- 239000012528 membrane Substances 0.000 claims 1
- 229940071648 metered dose inhaler Drugs 0.000 claims 1
- 210000004877 mucosa Anatomy 0.000 claims 1
- 239000006199 nebulizer Substances 0.000 claims 1
- 230000000414 obstructive effect Effects 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 230000000065 osmolyte Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 1
- 229940044601 receptor agonist Drugs 0.000 claims 1
- 239000000018 receptor agonist Substances 0.000 claims 1
- 239000012266 salt solution Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 238000005507 spraying Methods 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61K31/4965—Non-condensed pyrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P1/10—Laxatives
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- A61P11/08—Bronchodilators
-
- 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
- A61P11/12—Mucolytics
-
- 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
- A61P11/14—Antitussive agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
-
- 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
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- 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
- 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
- A61P27/16—Otologicals
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
- C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
- C07D241/30—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms in which said hetero-bound carbon atoms are part of a substructure —C(=X)—X—C(=X)—X— in which X is an oxygen or sulphur atom or an imino radical, e.g. imidoylguanidines
- C07D241/32—(Amino-pyrazinoyl) guanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
- C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
- C07D241/34—(Amino-pyrazine carbonamido) guanidines
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Gynecology & Obstetrics (AREA)
- Communicable Diseases (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
Claims (53)
1. Соединение формулы:
где Ar представляет собой фрагмент молекулы, выбранный из группы:
X выбран из -CH2-, -O- или -S-;
R1 и R2 независимо выбраны из H и C1-C6 алкила;
или R1 и R2 вместе с атомом азота, с которым они соединены связью, формируют 5-членное или 6-членное гетероциклическое кольцо, необязательно содержащее один дополнительный гетероатом в цикле, выбранный из N или O;
R3 представляет собой алкильную группу, содержащую от 3 до 8 атомов углерода, или полигидроксилированную алкильную группу, содержащую от 3 до 8 атомов углерода;
R4 представляет собой полигидроксилированную алкильную группу, содержащую от 3 до 8 атомов углерода;
R5 выбран из H или C1-C3 алкила;
или его фармацевтически приемлемая соль.
2. Соединение по п.1 формулы:
где R1 и R2 независимо выбраны из H и C1-C6 алкила;
или R1 и R2 вместе с атомом азота, с которым они соединены связью, формируют 5-членное или 6-членное гетероциклическое кольцо, необязательно содержащее один дополнительный гетероатом в цикле, выбранный из N или O;
R3 представляет собой алкильную группу, содержащую от 3 до 8 атомов углерода, или полигидроксилированную алкильную группу, содержащую от 3 до 8 атомов углерода;
R4 представляет собой полигидроксилированную алкильную группу, содержащую от 3 до 8 атомов углерода; и
R5 выбран из H или C1-C3 алкила;
или его фармацевтически приемлемая соль.
3. Соединение по п.1 или 2, в котором R3 полигидроксилированная алкильная группа имеет формулу -CH2-(CHR5)n, где n представляет собой целое число, выбранное из 2, 3, 4, 5, 6 или 7, и R5, независимо, в каждом случае, представляет собой H или OH при условии, что, по меньшей мере, две из R5 групп представляют собой OH, или его фармацевтически приемлемая соль.
4. Соединение по п.1, 2 или 3, в котором полигидроксилированная алкильная группа имеет формулу -CH2-CHOH-(CHR6)m, где m представляет собой целое число, выбранное из 1, 2, 3, 4, 5 или 6, и R6, независимо, в каждом случае, представляет собой H или OH при условии, что, по меньшей мере, одна из R6 групп представляют собой OH, или его фармацевтически приемлемая соль.
5. Соединение по п.1, 2, 3 или 4, в котором полигидроксилированная алкильная группа имеет формулу -CH2-(CHOH)n-CH2OH, где n представляет собой целое число, выбранное из 1, 2, 3, 4, 5 или 6, или его фармацевтически приемлемая соль.
6. Соединение по п.1, 2, 3, 4 или 5, в котором полигидроксилированная алкильная группа имеет формулу:
или его фармацевтически приемлемая соль.
7. Соединение по п.1, 2, 3, 4, 5 или 6, в котором полигидроксилированная алкильная группа имеет формулу:
или его фармацевтически приемлемая соль.
8. Соединение по п.1, 2, 3, 4, 5, 6 или 7, имеющее формулу, выбранную из группы:
или его фармацевтически приемлемая соль.
9. Фармацевтическая композиция, включающая фармацевтически эффективное количество соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли, и фармацевтически приемлемый носитель или наполнитель.
10. Композиция по п.9, где указанная композиция подходит для ингаляции.
11. Композиция по п.9 или 10, где указанная композиция представляет собой раствор для распыления в виде аэрозоля и введения с помощью распылителя, дозирующего ингалятора или ингалятора сухого порошка.
12. Композиция по п.9, 10 или 11, дополнительно включающая фармацевтически эффективное количество терапевтически активного агента, выбранного из противовоспалительных средств, антихолинергических средств, бета-агонистов, модуляторов муковисцидозного трансмембранного регулятора проводимости (CFTR), агонистов P2Y2-рецепторов, агонистов гамма-рецептора, активируемого пролифератором пероксисом, ингибиторов киназы, противоинфекционных средств и антигистаминных средств.
13. Способ, включающий введение человеку эффективного количества соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли.
14. Способ блокирования натриевых каналов у человека, включающий введение указанному человеку эффективного количества соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли.
15. Способ стимулирования гидратации поверхности слизистой оболочки или восстановления защиты слизистой оболочки у человека, включающий введение указанному человеку эффективного количества соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли.
16. Способ лечения заболевания, выбранного из обратимой или необратимой обструкции верхних дыхательных путей, хронической обструктивной болезни легких (ХОБЛ), астмы, бронхоэктаза (включая бронхоэктаз вследствие состояний, отличных от кистозного фиброза), острого бронхита, хронического бронхита, поствирусного кашля, кистозного фиброза, эмфиземы, пневмонии, панбронхиолита, бронхиолита после трансплантации и вентиляторно-ассоциированного трахеобронхита или профилактики вентиляторно-ассоциированной пневмонии у нуждающегося в этом человека, причем указанный способ включает введение указанному человеку эффективного количества соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли.
17. Способ лечения сухости во рту (ксеростомии), сухой кожи, вагинальной сухости, синусита, риносинусита или обезвоживания слизистой оболочки носа, включая обезвоживание слизистой оболочки носа, вызванное применением сухого кислорода, сухого кератита или болезни Шегрена, стимуляции гидратация глазного яблока и роговицы, лечения синдрома дистальной кишечной непроходимости, лечения среднего отита, первичной цилиарной дискинезии, синдрома дистальной кишечной непроходимости, эзофагита, запора или хронического дивертикулита у нуждающегося в этом человека, причем указанный способ включает введение указанному человеку эффективного количества соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли.
18. Соединение по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемая соль, предназначенное для применения в качестве лекарственного средства.
19. Соединение по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемая соль, предназначенное для применения при терапии заболевания, связанного с обратимой или необратимой обструкцией верхних дыхательных путей, хронической обструктивной болезнью легких (ХОБЛ), астмой, бронхоэктазом (включая бронхоэктаз вследствие состояний, отличных от кистозного фиброза), острым бронхитом, хроническим бронхитом, поствирусным кашлем, кистозным фиброзом, эмфиземой, пневмонией, панбронхиолитом, бронхиолитом после трансплантации и вентиляторно-ассоциированным трахеобронхитом, или при профилактике вентиляторно-ассоциированной пневмонии у человека, при необходимости этого.
20. Соединение по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемая соль, предназначенное для лечения сухости во рту (ксеростомии), сухой кожи, вагинальной сухости, синусита, риносинусита или обезвоживания слизистой оболочки носа, включая обезвоживание слизистой оболочки носа, вызванное применением сухого кислорода, сухого кератита или болезни Шегрена, стимуляции гидратация глазного яблока и роговицы, лечения синдрома дистальной кишечной непроходимости, лечения среднего отита, первичной цилиарной дискинезии, синдрома дистальной кишечной непроходимости, эзофагита, запора или хронического дивертикулита у человека, при необходимости этого.
21. Применение соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли, для изготовления лекарственного средства для лечения заболевания, связанного с обратимой или необратимой обструкцией верхних дыхательных путей, хронической обструктивной болезнью легких (ХОБЛ), астмой, бронхоэктазом (включая бронхоэктаз вследствие состояний, отличных от кистозного фиброза), острым бронхитом, хроническим бронхитом, поствирусным кашлем, кистозным фиброзом, эмфиземой, пневмонией, панбронхиолитом, бронхиолитом после трансплантации и вентиляторно-ассоциированным трахеобронхитом, или для профилактики вентиляторно-ассоциированной пневмонии у человека.
22. Применение соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли, для изготовления лекарственного средства для лечения сухости во рту (ксеростомии), сухой кожи, вагинальной сухости, синусита, риносинусита или обезвоживания слизистой оболочки носа, включая обезвоживание слизистой оболочки носа, вызванное применением сухого кислорода, сухого кератита или болезни Шегрена, стимуляции гидратация глазного яблока и роговицы, лечения синдрома дистальной кишечной непроходимости, лечения среднего отита, первичной цилиарной дискинезии, синдрома дистальной кишечной непроходимости, эзофагита, запора или хронического дивертикулита.
23. Композиция, включающая соединение по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемую соль, предназначенная для получения лекарственного средства для лечения заболевания, связанного с обратимой или необратимой обструкцией верхних дыхательных путей, хронической обструктивной болезнью легких (ХОБЛ), астмой, бронхоэктазом (включая бронхоэктаз вследствие состояний, отличных от кистозного фиброза), острым бронхитом, хроническим бронхитом, поствирусным кашлем, кистозным фиброзом, эмфиземой, пневмонией, панбронхиолитом, бронхиолитом после трансплантации и вентиляторно-ассоциированным трахеобронхитом, или для профилактики вентиляторно-ассоциированной пневмонии у человека.
24. Композиция, включающая соединение по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемую соль, предназначенная для получения лекарственного средства для лечения сухости во рту (ксеростомии), сухой кожи, вагинальной сухости, синусита, риносинусита или обезвоживания слизистой оболочки носа, включая обезвоживание слизистой оболочки носа, вызванное применением сухого кислорода, сухого кератита или болезни Шегрена, стимуляции гидратация глазного яблока и роговицы, лечения синдрома дистальной кишечной непроходимости, лечения среднего отита, первичной цилиарной дискинезии, синдрома дистальной кишечной непроходимости, эзофагита, запора или хронического дивертикулита.
25. Способ профилактики, облегчения и/или лечения детерминированных воздействий на состояние дыхательных путей и/или других органов, вызванных вдыхаемыми аэрозолями, содержащими радионуклиды, у нуждающегося в этом человека, причем указанный способ включает введение указанному человеку эффективного количества соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли.
26. Фармацевтическая композиция, включающая фармацевтически эффективное количество соединения по п.1, 2, 3, 4, 5, 6, 7 или 8, или его фармацевтически приемлемой соли, и осмолит.
27. Фармацевтическая композиция по п.26, в которой осмолит представляет собой гипертонический раствор соли.
28. Фармацевтическая композиция по п.26, в которой осмолит представляет собой маннитол.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261738235P | 2012-12-17 | 2012-12-17 | |
US61/738,235 | 2012-12-17 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2015129062A Division RU2671976C2 (ru) | 2012-12-17 | 2013-12-13 | Соединения 3,5-диамино-6-хлор-n-(n-(4-фенилбутил)карбамимидоил)пиразин-2-карбоксамида |
Publications (1)
Publication Number | Publication Date |
---|---|
RU2018138195A true RU2018138195A (ru) | 2018-12-18 |
Family
ID=50931176
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2018138195A RU2018138195A (ru) | 2012-12-17 | 2013-12-13 | Соединения 3,5-диамино-6-хлор-n-(n-(4- фенилбутил)карбамимидоил)пиразин-2-карбоксамида |
RU2015129062A RU2671976C2 (ru) | 2012-12-17 | 2013-12-13 | Соединения 3,5-диамино-6-хлор-n-(n-(4-фенилбутил)карбамимидоил)пиразин-2-карбоксамида |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2015129062A RU2671976C2 (ru) | 2012-12-17 | 2013-12-13 | Соединения 3,5-диамино-6-хлор-n-(n-(4-фенилбутил)карбамимидоил)пиразин-2-карбоксамида |
Country Status (13)
Country | Link |
---|---|
US (4) | US9029382B2 (ru) |
EP (2) | EP2931712B8 (ru) |
JP (2) | JP6392241B2 (ru) |
KR (1) | KR20150095870A (ru) |
CN (2) | CN104995178B (ru) |
AU (2) | AU2013363215B2 (ru) |
BR (1) | BR112015014178A2 (ru) |
IL (2) | IL239409A (ru) |
MX (1) | MX2015007797A (ru) |
NZ (1) | NZ709197A (ru) |
RU (2) | RU2018138195A (ru) |
WO (1) | WO2014099673A1 (ru) |
ZA (1) | ZA201504561B (ru) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6858615B2 (en) | 2002-02-19 | 2005-02-22 | Parion Sciences, Inc. | Phenyl guanidine sodium channel blockers |
DK3219705T3 (da) | 2005-12-28 | 2020-04-14 | Vertex Pharma | Farmaceutiske sammensætninger af den amorfe form af n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinolin-3-carboxamid |
AR086745A1 (es) | 2011-06-27 | 2014-01-22 | Parion Sciences Inc | 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida |
EP2723176B1 (en) | 2011-06-27 | 2017-04-12 | Parion Sciences, Inc. | A chemically and metabolically stable dipeptide possessing potent sodium channel blocker activity |
EP3366680B1 (en) | 2012-05-29 | 2020-05-13 | Parion Sciences, Inc. | Dendrimer like amino amides possessing sodium channel blocker activity for the treatment of dry eye and other mucosal diseases |
JP6392241B2 (ja) | 2012-12-17 | 2018-09-19 | パリオン・サイエンシィズ・インコーポレーテッド | 3,5−ジアミノ−6−クロロ−n−(n−(4−フェニルブチル)カルバムイミドイル)ピラジン−2−カルボキサミド化合物 |
DK2931713T3 (en) | 2012-12-17 | 2017-01-30 | Parion Sciences Inc | CHLORPYRAZINE CARBOXAMIDE DERIVATIVES USED FOR THE TREATMENT OF DISEASES BENEFITED BY INDEPENDENT MOSPHEREWIN |
JP6596421B2 (ja) | 2013-08-23 | 2019-10-23 | パリオン・サイエンシィズ・インコーポレーテッド | ジチオール粘液溶解薬 |
US9102633B2 (en) | 2013-12-13 | 2015-08-11 | Parion Sciences, Inc. | Arylalkyl- and aryloxyalkyl-substituted epithelial sodium channel blocking compounds |
UY36034A (es) | 2014-03-18 | 2015-09-30 | Astrazeneca Ab | Derivados de 3,5-diamino-6-cloro-pirazina-2-carboxamida y sales farmaceuticamente aceptables de estos |
US20150376145A1 (en) | 2014-06-30 | 2015-12-31 | Parion Sciences, Inc. | Stable sodium channel blockers |
AU2015328174B2 (en) | 2014-10-06 | 2020-05-21 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
JP6746569B2 (ja) | 2014-10-07 | 2020-08-26 | バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated | 嚢胞性線維症膜貫通コンダクタンス制御因子のモジュレーターの共結晶 |
CN107614480B (zh) | 2015-01-30 | 2020-09-15 | 帕里昂科学公司 | 新型单硫醇粘液溶解剂 |
EP3244893A4 (en) * | 2015-02-18 | 2019-01-09 | Parion Sciences, Inc. | SODIUM CHANNEL BLOCKER FOR SKIN DISEASES |
AU2016255851A1 (en) | 2015-04-30 | 2017-12-14 | Parion Sciences, Inc. | Novel prodrugs of dithiol mucolytic agents |
GB201610854D0 (en) | 2016-06-21 | 2016-08-03 | Entpr Therapeutics Ltd | Compounds |
GB201619694D0 (en) | 2016-11-22 | 2017-01-04 | Entpr Therapeutics Ltd | Compounds |
GB201717051D0 (en) * | 2017-10-17 | 2017-11-29 | Enterprise Therapeutics Ltd | Compounds |
GB201808093D0 (en) | 2018-05-18 | 2018-07-04 | Enterprise Therapeutics Ltd | Compounds |
EP3921033B1 (en) * | 2019-02-08 | 2023-07-26 | AstraZeneca AB | Arginase inhibitors and methods of use thereof |
US20220265583A1 (en) * | 2019-07-30 | 2022-08-25 | The Regents Of The University Of California | Methods and composition for treating respiratory obstructive diseases |
WO2021183371A1 (en) * | 2020-03-11 | 2021-09-16 | Purdue Research Foundation | Nano-composite microparticles of polymyxin |
WO2023229667A1 (en) * | 2022-05-24 | 2023-11-30 | The Cleveland Clinic Foundation | Topical angiotensin ii receptor blockers (arbs) for treating eye conditions |
Family Cites Families (413)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3268406A (en) | 1961-10-12 | 1966-08-23 | Merck & Co Inc | Compositions and method of using (3-amino-pyrazinoyl) guanidines |
BE639386A (ru) | 1962-10-30 | |||
DK109779C (da) | 1962-10-30 | 1968-07-01 | Merck & Co Inc | Fremgangsmåde til fremstilling af 3-aminopyrazinamidoguanidinforbindelser eller syreadditionssalte heraf. |
NL6409716A (ru) | 1962-10-30 | 1965-10-01 | ||
US3316266A (en) | 1964-03-31 | 1967-04-25 | Merck & Co Inc | 3-aminopyrazinoic acid derivatives and process for their preparation |
BE639393A (ru) | 1962-10-30 | |||
NL6409714A (ru) | 1962-10-30 | 1965-10-01 | ||
US3274191A (en) | 1963-11-15 | 1966-09-20 | Merck & Co Inc | N-(3-aminopyrazinoyl) benzamidines and process for preparing |
US3240780A (en) | 1963-12-23 | 1966-03-15 | Merck & Co Inc | Amino-pyrazinoyl guanidines |
DE1245967B (de) | 1964-03-31 | 1967-08-03 | Merck &. Co., Inc., Rahway, N.J. (V. St. A.) | Verfahren zur Herstellung von S.S-Diamino-o-chlor-pyrazincarbonsäurealkylestern |
NL6501301A (ru) | 1964-04-03 | 1965-10-04 | ||
US3249610A (en) | 1964-09-08 | 1966-05-03 | Merck & Co Inc | Synthesis of 3-amino, 5-chloro, 6-substituted-pyrazinoates |
DE1281818B (de) | 1965-07-17 | 1968-10-31 | Rheinische Kalksteinwerke | Verfahren zum gleichzeitigen Mahlen mehrerer Rohstoffe unterschiedlicher Mahlbarkeit |
US3318813A (en) | 1965-08-16 | 1967-05-09 | Dow Chemical Co | Poly-alkylstyrene viscosity index improver |
US3341540A (en) | 1965-10-04 | 1967-09-12 | Merck & Co Inc | 3-amino-6-halopyrazinonitriles and their syntheses |
US3274192A (en) | 1965-10-04 | 1966-09-20 | Merck & Co Inc | Derivatives of pyrazine and a method for their preparation |
US3305552A (en) | 1965-11-22 | 1967-02-21 | Merck & Co Inc | 3-aminopyrazinoic acids and process for their preparation |
US3361748A (en) | 1965-11-22 | 1968-01-02 | Merck & Co Inc | Process for the preparation of pteridinones |
US3361306A (en) | 1966-03-31 | 1968-01-02 | Merck & Co Inc | Aerosol unit dispensing uniform amounts of a medically active ingredient |
NL6707564A (ru) | 1966-08-25 | 1968-02-26 | ||
IL27897A (en) | 1966-08-25 | 1972-02-29 | Merck & Co Inc | Preparation of pyrazinoalguanides and pyrazinoamidoguanidines |
FR1525670A (fr) | 1966-08-25 | 1968-05-17 | Merck & Co Inc | Procédé de fabrication de guanidines substituées |
FR1525671A (fr) | 1966-08-25 | 1968-05-17 | Merck & Co Inc | Procédé de préparation de (3, 5 - diamino - 6 - halogéno - pyrazinoyl) - guanidines et de (3, 5 - diamino - 6 - halogéno -pyrazinamido) guanidines |
US3660400A (en) | 1966-11-17 | 1972-05-02 | Merck & Co Inc | Lower alkyl 3-hydroxy and 3-mercaptopyrazinoates |
US3472848A (en) | 1966-11-17 | 1969-10-14 | Merck & Co Inc | 3-hydroxy and 3-mercapto-pyrazinoyl-guanidines,corresponding ethers and thioethers and processes for their preparation |
US3527758A (en) | 1967-04-13 | 1970-09-08 | Merck & Co Inc | Process for the preparation of pyrazinoylguanidines from a pyrazinoic azide and a guanidine |
US3507865A (en) | 1967-04-27 | 1970-04-21 | Merck & Co Inc | 3-hydroxy- and 3-mercaptopyrazinamidoguanidines the corresponding ethers and thioethers and processes for their preparation |
US3507866A (en) | 1967-08-08 | 1970-04-21 | Merck & Co Inc | 1h - imidazo(4,5-b)pyrazin - 2 - one and processes for their preparation |
US3487082A (en) | 1967-09-28 | 1969-12-30 | Merck & Co Inc | 2,4 - diamino - 6 - halopteridines and processes for their preparation |
US3503973A (en) | 1967-11-07 | 1970-03-31 | Merck & Co Inc | Process for preparation of pyrazinoylguanidines |
US3515723A (en) | 1967-11-14 | 1970-06-02 | Merck & Co Inc | 2 - (5 - amino - 1h - 1,2,4 - triazol - 3 - yl)- 3-aminopyrazines and processes for their preparation |
US3531484A (en) | 1968-02-14 | 1970-09-29 | Merck & Co Inc | 1-(3-aminopyrazinoyl)-4,5,5-trisubstituted biguanide products |
US3461123A (en) | 1968-04-12 | 1969-08-12 | Merck & Co Inc | 1h-imidazo(4,5-b)pyrazin-2-ones and processes for their preparation |
US3506662A (en) | 1968-04-30 | 1970-04-14 | Merck & Co Inc | Process for preparation of pyrazinoyland pyrazinamidoguanidines |
US3625950A (en) | 1968-07-03 | 1971-12-07 | Merck & Co Inc | Certain halophenoxy alkanamides, hydrazides and derivatives thereof |
US3575975A (en) | 1968-07-25 | 1971-04-20 | Merck & Co Inc | Process for the preparation of 3-aminopyrazinoylureas |
US3539569A (en) | 1968-08-21 | 1970-11-10 | Merck & Co Inc | Preparation of pyrazinoylguanidines from pyrazinoylureas |
US3544571A (en) | 1968-09-04 | 1970-12-01 | Merck & Co Inc | Process for making pyrazinoylthiourea compounds |
US3555023A (en) | 1968-11-13 | 1971-01-12 | Merck & Co Inc | 1-(3 - aminopyrazinoyl) - 3 - substituted-3-thioisosemicarbazides and method for preparation |
US3555024A (en) | 1968-11-13 | 1971-01-12 | Merck & Co Inc | 1-(3-aminopyrazinoyl)semicarbazides,1-(3-aminopyrazinoyl) - thiosemicarbazides,and method for their preparation |
US3668241A (en) | 1968-11-25 | 1972-06-06 | Merck & Co Inc | Substituted 1-oxoinden-5-yloxy alkanoic acids |
US3586688A (en) | 1968-12-18 | 1971-06-22 | Merck & Co Inc | Certain aminopyridinecarbonyl guanidines |
US3573305A (en) | 1968-12-30 | 1971-03-30 | Merck & Co Inc | (3-amino-pyrazinoyl)sulfamides and their preparation |
US3577418A (en) | 1969-02-12 | 1971-05-04 | Merck & Co Inc | Pyrazinamide derivatives and processes for their preparation |
US3565070A (en) | 1969-02-28 | 1971-02-23 | Riker Laboratories Inc | Inhalation actuable aerosol dispenser |
US3573306A (en) | 1969-03-05 | 1971-03-30 | Merck & Co Inc | Process for preparation of n-substituted 3,5-diamino-6-halopyrazinamides |
US3544568A (en) | 1969-03-18 | 1970-12-01 | Merck & Co Inc | 3-amino-5,6-substituted pyrazinamides |
US3660397A (en) | 1970-04-17 | 1972-05-02 | Merck & Co Inc | Imidazo(4 5-b)pyrazines |
US3864401A (en) | 1970-12-23 | 1975-02-04 | Merck & Co Inc | Substituted 2-aminomethyl-4,6-dihalophenols |
US3794734A (en) | 1971-03-03 | 1974-02-26 | Merck & Co Inc | Methods of treating edema and hypertension using certain 2-aminoethylphenols |
US3935313A (en) | 1971-03-29 | 1976-01-27 | Jan Marcel Didier Aron-Samuel | Pharmaceutical composition containing N-(3-diethyl-aminopropyl)-4-nitro-1-oxide-pyridine-2-carboxamide and process for the treatment of hypertension therewith |
US3948895A (en) | 1971-09-28 | 1976-04-06 | E. I. Du Pont De Nemours And Company | Synthesis of 3,5-diaminopyrazinoic acid from 3,5-diamino-2,6-dicyanopyrazine and intermediates |
BE791201A (fr) | 1971-11-12 | 1973-05-10 | Merck & Co Inc | Indanyloxytetrazoles |
US3953476A (en) | 1971-12-27 | 1976-04-27 | Merck & Co., Inc. | 3-Amino-5-sulfonylbenzoic acids |
US3894085A (en) | 1972-09-19 | 1975-07-08 | Ciba Geigy Corp | New 2-halo nitrones, their manufacture and their use for the manufacture of N-substituted araliphatic aldehyde-nitrones |
US4085219A (en) | 1972-10-13 | 1978-04-18 | Merck & Co., Inc. | 1-Oxo-2,2-disubstituted-5-indanyloxy(or thio)alkanoic acids |
US3984465A (en) | 1972-10-13 | 1976-10-05 | Merck & Co., Inc. | 1-Oxo-2,2-disubstituted-5-indanyloxy(or thio)alkanoic acids |
US4081554A (en) | 1972-10-13 | 1978-03-28 | Merck & Co., Inc. | 1-oxo-2,2-disubstituted-5-indanyloxy(or thio)alkano acids |
US3976686A (en) | 1972-10-13 | 1976-08-24 | Merck & Co., Inc. | [1-Oxo-2,3-hydrocarbylene-5-indanyloxy(or thio)]alkanoic acids |
US4091015A (en) | 1972-10-27 | 1978-05-23 | American Home Products Corporation | 15-Substituted prostanoic acids |
US4092356A (en) | 1972-10-30 | 1978-05-30 | Merck & Co., Inc. | 11,12-Secoprostaglandins |
US4066692A (en) | 1972-10-30 | 1978-01-03 | Merck & Co., Inc. | 11,12-secoprostaglandins |
US4055597A (en) | 1973-01-26 | 1977-10-25 | Merck & Co., Inc. | 10-Aza-11,12-secoprostaglandins |
US3987091A (en) | 1973-04-12 | 1976-10-19 | Merck & Co., Inc. | 11,12-secoprostaglandins |
US4091107A (en) | 1973-04-25 | 1978-05-23 | Merck & Co., Inc. | 8-Aza-9-oxo(and dioxo)-thia-11,12-secoprostaglandins |
US4033996A (en) | 1973-04-25 | 1977-07-05 | Merck & Co., Inc. | 8-Aza-9-oxo(and dioxo)-thia-11,12-secoprostaglandins |
US3894065A (en) | 1973-04-27 | 1975-07-08 | Merck & Co Inc | Aryl-oxo-alkanoic acids |
US4177285A (en) | 1973-10-11 | 1979-12-04 | Merck & Co., Inc. | [1-Oxo-2-thienyl-2-substituted-5-indanyloxy (or thio)]alkanoic acids and derivatives thereof |
US4182764A (en) | 1973-10-11 | 1980-01-08 | Merck & Co., Inc. | Tetrazole derivatives of [1-oxo-2-aryl or thienyl-2-substituted-5-indanyloxy(or thio)]alkanoic acids |
US4012524A (en) | 1973-10-12 | 1977-03-15 | Merck & Co., Inc. | [1-Hydroxy-5-indanyloxy (or thio)]-alkanoic acids |
US3929872A (en) | 1973-10-12 | 1975-12-30 | Merck & Co Inc | Indanacetic acid compounds |
US3966966A (en) | 1973-10-12 | 1976-06-29 | Merck & Co., Inc. | Pharmaceutical compositions and method of treatment employing 1,3-dioxo-2,2-disubstituted indanyloxy alkanoic acids |
US4006180A (en) | 1973-10-12 | 1977-02-01 | Merck & Co., Inc. | [1,3-Dihydroxy-2-substituted and 2,2-disubstituted-indanyloxy(or thio)]alkanoic acids |
US3976681A (en) | 1973-10-12 | 1976-08-24 | Merck & Co., Inc. | [1,3-Dioxo-2-substituted and 2,2-disubstituted- indanyloxy (or thio] alkanoic acids |
US4003927A (en) | 1973-10-12 | 1977-01-18 | Merck & Co., Inc. | (1-Oxo-7,8-disubstituted-1,2,3,4-tetrahydro-6-naphthyloxy)- and (3,4-disubstituted-5-oxo-6,7,8,9-tetrahydro-5H-benzocycloheptene-2-yloxy) acetic acids and derivatives |
US3989749A (en) | 1973-10-17 | 1976-11-02 | Merck & Co., Inc. | 11,12-Secoprostaglandins |
US3991087A (en) | 1973-12-13 | 1976-11-09 | Merck & Co., Inc. | 8-Halo-11,12-secoprostaglandins |
US3979361A (en) | 1974-02-20 | 1976-09-07 | Merck & Co., Inc. | 2-Aminomethyl-6-trihalo-methylphenols |
US3914253A (en) | 1974-03-04 | 1975-10-21 | Merck & Co Inc | 5-Oxo-6-substituted-cyclopent-{8 f{9 -indole-2-carboxylic acids |
US3931239A (en) | 1974-04-03 | 1976-01-06 | Merck & Co., Inc. | 6-Oxo-7-substituted-6H-indeno-[5,4-b]furan(and thiophene)-carboxylic acids |
US3958004A (en) | 1974-04-23 | 1976-05-18 | Merck & Co., Inc. | Phenoxyacetic acid derivatives as uricosuric agents |
US3928624A (en) | 1974-04-25 | 1975-12-23 | Merck & Co Inc | Phenol compounds in treating pain, fever and inflammation |
US3956374A (en) | 1974-05-03 | 1976-05-11 | Merck & Co., Inc. | Aryl-oxo-heptenoic acids |
US3974212A (en) | 1974-05-22 | 1976-08-10 | Merck & Co., Inc. | [1-Hydroximino-2,2-disubstituted-5-indanyloxy-(or thio)]alkanoic acids |
AT351182B (de) | 1974-06-25 | 1979-07-10 | Merck & Co Inc | Verfahren zur herstellung von neuen 9-thia-, 9-oxothia- und 9-dioxothia- 11,12-secoprosta- glandinen |
PL98342B1 (pl) | 1974-07-30 | 1978-04-29 | Sposob wytwarzania kwasu 1-keto-2-arylo-/lub tienylo/-2-podstawionego-indanyloksy-/lub tio/-5-alkanokarboksylowego | |
US4020177A (en) | 1974-08-30 | 1977-04-26 | Merck & Co., Inc. | Substituted phenoxy-tridecanoic acids |
US3991106A (en) | 1974-09-13 | 1976-11-09 | Merck & Co., Inc. | 16-Ethers of 8-aza-9-dioxothia-11,12-seco-prostaglandins |
US4055596A (en) | 1974-09-13 | 1977-10-25 | Merck & Co., Inc. | 11,12-Seco-prostaglandins |
US3984552A (en) | 1975-02-24 | 1976-10-05 | Merck & Co., Inc. | 6-Oxo-7-substituted and 7,7-disubstituted-6H-indeno-[5,4-b]furan (and thiophene) carboxylic acids |
JPS51116341A (en) | 1975-04-04 | 1976-10-13 | Automob Antipollut & Saf Res Center | Detection apparatus for oil pressure |
US4018802A (en) | 1975-04-09 | 1977-04-19 | Merck & Co., Inc. | 9-Thia- and oxothia- and 9-dioxothia-11,12-seco-prostaglandins and processes |
US4097504A (en) | 1975-04-23 | 1978-06-27 | Merck & Co., Inc. | 11,12-Secoprostaglandins |
US4092414A (en) | 1975-04-25 | 1978-05-30 | Merck & Co., Inc. | 3,4-Dihydrospiro-2H-1,3-benzoxazines and their use in treating edema, abnormal electrolyte retention, and inflammation |
US4059601A (en) | 1975-06-06 | 1977-11-22 | Merck & Co., Inc. | 8-Halo-11,12-secoprostaglandins |
US4059602A (en) | 1975-06-06 | 1977-11-22 | Merck & Co., Inc. | 8-Methyl-, phenyl-, or substituted phenyl-11,12-secoprostaglandins |
US4061643A (en) | 1975-06-18 | 1977-12-06 | Merck & Co., Inc. | Certain 16-aryloxy-11,12-seco-prostaglandins |
US4296122A (en) | 1975-07-09 | 1981-10-20 | Merck & Co., Inc. | 2,3-Dihydro-6,7-disubstituted-5-(acyl)benzofuran-2-carboxylic acids |
US4181727A (en) | 1975-07-09 | 1980-01-01 | Merck & Co., Inc. | 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids |
US4087542A (en) | 1975-07-09 | 1978-05-02 | Merck & Co., Inc. | 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids |
US4044153A (en) | 1975-08-01 | 1977-08-23 | Merck & Co., Inc. | Antiinflammatory 2-aminomethyl-6-trihalomethylphenols |
US4203988A (en) | 1975-11-12 | 1980-05-20 | Merck & Co., Inc. | Pyridinyl ureas and pharmaceutical use |
US4029816A (en) | 1975-11-25 | 1977-06-14 | Merck & Co., Inc. | Substituted 2-aminomethyl-6-iodophenols |
US4085211A (en) | 1975-12-15 | 1978-04-18 | Merck & Co., Inc. | Pyrazinecarboxamides and processes for preparing same |
US4070464A (en) | 1976-02-19 | 1978-01-24 | Merck & Co., Inc. | Method of treating autoimmune diseases |
US4128564A (en) | 1976-03-22 | 1978-12-05 | Merck & Co., Inc. | 9-Thia- and oxothia- and 9-dioxothia-11,12-seco-prostaglandins |
US4085125A (en) | 1976-03-22 | 1978-04-18 | Merck & Co., Inc. | 9-Thia-, 9-oxothia-, and 9-dioxothia-11,12-seco-prostaglandins and processes |
US4029803A (en) | 1976-05-03 | 1977-06-14 | Merck & Co., Inc. | Method of treatment with 2-iminothiazolidines and thiazolines |
US4181661A (en) | 1976-05-03 | 1980-01-01 | Merck & Co., Inc. | Derivatives of 2-iminothiazolidines and thiazolines |
US4022794A (en) | 1976-05-24 | 1977-05-10 | Merck & Co., Inc. | Novel analogs of prostaglandins with 4-oxo-thiazolidinyl nucleus and method of preparation thereof |
US4059587A (en) | 1976-05-24 | 1977-11-22 | Merck & Co., Inc. | Certain thiazolidine compounds |
US4054652A (en) | 1976-06-15 | 1977-10-18 | Merck & Co., Inc. | Dihydro- and tetrahydro- iminothiazines |
US4025625A (en) | 1976-06-15 | 1977-05-24 | Merck & Co., Inc. | Imidazothiazines |
NL7705652A (nl) | 1976-06-15 | 1977-12-19 | Merck & Co Inc | 2-imino-3-aminothiazolidinen. |
US4087526A (en) | 1976-07-23 | 1978-05-02 | Merck & Co., Inc. | (3-Amino-5-substituted-6-fluoropyrazinoyl or pyrazamido)-guanidines and their derivatives bearing substituents on the guanidino nitrogens |
US4111877A (en) | 1976-07-29 | 1978-09-05 | Air Products & Chemicals, Inc. | Allyl esters of n-alkyl-omega-(alkyleneureido) amic acids and their synthesis and use in aqueous emulsion polymer systems |
US4067980A (en) | 1976-08-16 | 1978-01-10 | Merck & Co., Inc. | Spirobenzoxazinium salts, method of use and compositions thereof as antihypertensive agents |
US4085117A (en) | 1976-10-18 | 1978-04-18 | Merck & Co., Inc. | 6,7-Disubstituted-5-(acyl)benzofuran-2-carboxylic acids |
US4100294A (en) | 1976-12-06 | 1978-07-11 | Merck & Co., Inc. | 5-(Hydroxy (substituted) methyl)-2,3-dihydrobenzo furan-2-carboxylic acid and its derivatives |
US4150235A (en) | 1976-12-17 | 1979-04-17 | Merck & Co., Inc. | Interphenylene 11,12-secoprostaglandins |
US4175203A (en) | 1976-12-17 | 1979-11-20 | Merck & Co., Inc. | Interphenylene 11,12-secoprostaglandins |
US4105769A (en) | 1977-01-24 | 1978-08-08 | Merck & Co., Inc. | Inhibition of indoleamine-N-methyl transferase by 2-iminopyridines |
US4087435A (en) | 1977-02-17 | 1978-05-02 | Merck & Co., Inc. | 8-Aza-9-dioxothiaprostanoic acids |
US4115573A (en) | 1977-03-04 | 1978-09-19 | Merck & Co., Inc. | N-pyrazinecarbonyl-N'-substituted-sulfamoylguanidine and processes for preparing same |
US4208413A (en) | 1977-03-04 | 1980-06-17 | Merck & Co., Inc. | N-Pyrazinecarbonyl-N'-alkoxycarbonyl and N',N"-bis(alkoxycarbonyl)guanidines and processes for preparing same |
US4112236A (en) | 1977-04-04 | 1978-09-05 | Merck & Co., Inc. | Interphenylene 8-aza-9-dioxothia-11,12-secoprostaglandins |
US4108859A (en) | 1977-06-06 | 1978-08-22 | The Dow Chemical Company | Microbicidal (pyridinylamino) alkyl guanidines |
US4115402A (en) | 1977-06-17 | 1978-09-19 | Merck & Co., Inc. | 2,3-Dichloro-4-[(substituted-sulfonyl)-phenoxy]-acetic acids |
US4196292A (en) | 1977-06-29 | 1980-04-01 | Merck & Co., Inc. | 6-Substituted amiloride derivatives |
US4229456A (en) | 1977-07-18 | 1980-10-21 | Merck & Co., Inc. | Substituted naphthyridinones and processes for their preparations |
US4133885A (en) | 1977-07-18 | 1979-01-09 | Merck & Co., Inc. | Substituted naphthyridinones |
US4536507A (en) | 1977-07-26 | 1985-08-20 | Merck & Co., Inc. | Prostaglandin antagonists |
US4093728A (en) | 1977-08-18 | 1978-06-06 | E. R. Squibb & Sons, Inc. | Triazoloisoindoles |
US4140776A (en) | 1977-09-16 | 1979-02-20 | Merck & Co., Inc. | N-pyrazinecarbonyl-N'-acylguanidines |
US4130566A (en) | 1977-10-27 | 1978-12-19 | Sumitomo Chemical Company, Limited | Process for producing 5-carboxy-2-acetylthiophene |
US4127584A (en) | 1977-11-11 | 1978-11-28 | Merck & Co., Inc. | 2,3-Substituted-1,2,5-thiadiazolium salt antimicrobials |
US4159279A (en) | 1977-11-23 | 1979-06-26 | Merck & Co., Inc. | Nuclear substituted 2-hydroxyphenylmethanesulfamic acids |
US4292430A (en) | 1977-11-23 | 1981-09-29 | Merck & Co., Inc. | 2,3-Substituted-1,2-isothiazolium salt antimicrobials |
US4267341A (en) | 1977-11-23 | 1981-05-12 | Merck & Co., Inc. | Process for preparing 2,3-substituted-1,2,-isothiazolium salt antimicrobials |
US4166177A (en) | 1977-12-27 | 1979-08-28 | Merck & Co., Inc. | Substituted 2,2-dioxo-1,2,3-benzoxathiazines |
US4145551A (en) | 1978-01-09 | 1979-03-20 | Merck & Co., Inc. | Pyrazine-2-carbonyloxyguanidines |
US4401669A (en) | 1978-01-27 | 1983-08-30 | Merck & Co., Inc. | 2,3-Dihydro-substituted-5-benzoyl benzofuran-2-carboxylic acids and their use in treating hypertension |
US4189496A (en) | 1978-02-16 | 1980-02-19 | Merck & Co., Inc. | 2,3-Dihydro-5-thienylmethyl and furylmethyl-6-substituted and 6,7-disubstituted-benzofuran-2-carboxylic acid |
US4163781A (en) | 1978-04-17 | 1979-08-07 | Merck & Co., Inc. | 3-Amino-N-[(phosphonoamino)iminomethyl]-6-halopyrazinecarboxamide compounds, compositions and methods of use |
US4156005A (en) | 1978-06-21 | 1979-05-22 | Merck & Co., Inc. | Derivatives of 1,2-benzisoxazoles |
US4394515A (en) | 1978-06-23 | 1983-07-19 | Merck & Co., Inc. | 10,11-Dihydro-11-oxodibenzo[b,f]thiepin compounds |
US4263207A (en) | 1978-08-01 | 1981-04-21 | Merck & Co., Inc. | 10,11-Dihydrodibenzo[b,f][1,4]thiazepine carboxylic acids esters and amides thereof |
US4190655A (en) | 1978-08-28 | 1980-02-26 | Merck & Co., Inc. | Amiloride citrate |
US4226867A (en) | 1978-10-06 | 1980-10-07 | Merck & Co., Inc. | 3,3-Substituted spiro-1,2,4-benzothiadiazines |
US4178386A (en) | 1978-10-11 | 1979-12-11 | Merck & Co., Inc. | Inhibitors of glycolic acid oxidase |
US4187315A (en) | 1978-10-11 | 1980-02-05 | Merck & Co., Inc. | N-alkyl(and cycloalkyl)oxamic acid and derivatives as inhibitors of glycolic acid oxidase |
US4207329A (en) | 1978-10-11 | 1980-06-10 | Merck & Co., Inc. | Derivatives of glycolic and glyoxylic acid as inhibitors of glycolic acid oxidase |
US4342782A (en) | 1978-11-16 | 1982-08-03 | Merck & Co., Inc. | 1-(Substituted-aminoalkoxyphenyl)-2-methylene-1-alkanones, compositions and use thereof |
US4390537A (en) | 1978-11-16 | 1983-06-28 | Merck & Co., Inc. | 1-(Substituted-aminoalkoxyphenyl)-2-methylene-1-alkanones, compositions and use |
US4282365A (en) | 1978-11-24 | 1981-08-04 | Merck & Co., Inc. | Dibenz[b,e]oxepin compounds |
US4249021A (en) | 1979-02-26 | 1981-02-03 | Merck & Co., Inc. | Indanacetic acid compounds |
US4224447A (en) | 1979-03-27 | 1980-09-23 | Merck & Co., Inc. | Novel pyrazinecarboxamides and processes for preparing same |
US4246406A (en) | 1979-03-27 | 1981-01-20 | Merck & Co., Inc. | Heterocyclic substituted pyrazinoylguanidines |
US4221790A (en) | 1979-04-16 | 1980-09-09 | Merck & Co., Inc. | Substituted 2,2-dioxo-1,2,3-benzoxathiazines |
US4233452A (en) | 1979-05-03 | 1980-11-11 | Merck & Co., Inc. | Derivatives of glycolic and glyoxylic acid as inhibitors of glycolic acid oxidase |
US4220654A (en) | 1979-06-04 | 1980-09-02 | Merck & Co., Inc. | Cyclic imidazole cyanoguanidines |
US4256758A (en) | 1979-06-11 | 1981-03-17 | Merck & Co., Inc. | 4-Substituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4537902A (en) | 1979-06-11 | 1985-08-27 | Merck & Co., Inc. | 4-Substituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4431660A (en) | 1979-06-11 | 1984-02-14 | Merck & Co., Inc. | (4'-Biphenylyloxy and-thio-oxy)-3-hydroxy-3-pyrroline-2,5-diones and a method of treating calcium oxalate renal lithiasis therewith |
US4237144A (en) | 1979-06-21 | 1980-12-02 | Merck & Co., Inc. | 2,3-Dihydro-2,6,7-trisubstituted-5-acylbenzofurans |
US4291050A (en) | 1979-06-21 | 1981-09-22 | Merck & Co., Inc. | 6,7-Disubstituted-2 or 2,2-substituted-5-substituted-1-indanones |
US4237130A (en) | 1979-06-21 | 1980-12-02 | Merck & Co., Inc. | 2,3-Dihydro-6,7-disubstituted-5-(substituted sulfonyl)benzofuran-2-carboxylic acids |
JPS6034925B2 (ja) | 1979-07-31 | 1985-08-12 | 帝人株式会社 | 持続性鼻腔用製剤およびその製造法 |
US4375475A (en) | 1979-08-17 | 1983-03-01 | Merck & Co., Inc. | Substituted pyranone inhibitors of cholesterol synthesis |
US4459422A (en) | 1979-08-17 | 1984-07-10 | Merck & Co., Inc. | Substituted pyranone inhibitors of cholesterol synthesis |
US4567289A (en) | 1979-08-17 | 1986-01-28 | Merck & Co., Inc. | Substituted pyranone inhibitors of cholesterol synthesis |
US4710513A (en) | 1979-08-17 | 1987-12-01 | Merck & Co., Inc. | Substituted pyranone inhibitors of cholesterol synthesis |
US4379791A (en) | 1979-09-11 | 1983-04-12 | Merck & Co., Inc. | 4-(Substituted thiazolyl)-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4298743A (en) | 1979-09-11 | 1981-11-03 | Merck & Co., Inc. | 4-(Substituted phenyl thiazolyl)-3-hydroxy-3-pyrroline-2,5-diones |
US4377588A (en) | 1979-09-11 | 1983-03-22 | Merck Sharp & Dohme (I.A.) Corp. | 4-(Substituted thiazolyl)-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4296237A (en) | 1979-09-11 | 1981-10-20 | Merck & Co., Inc. | 4-(Pyridyl, piperazinyl and thiazolyl substituted thiazolyl)-3-hydroxy-3-pyrroline-2,5-diones |
US4317922A (en) | 1979-10-19 | 1982-03-02 | Merck & Co., Inc. | [(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acids and their analogs, esters, salts and derivatives |
US4356313A (en) | 1979-10-19 | 1982-10-26 | Merck & Co., Inc. | [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acid esters and their analogs, the parent acids and their salts |
US4337354A (en) | 1979-10-19 | 1982-06-29 | Merck & Co., Inc. | [(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acids, their analogs, esters, salts, and derivatives |
US4448786A (en) | 1979-11-05 | 1984-05-15 | Merck & Co., Inc. | 4-Naphthyl and substituted naphthyl-3-hydroxy-3-pyrroline-2,5-diones and their use as inhibitors of glycolic acid oxidase |
US4342776A (en) | 1979-11-05 | 1982-08-03 | Merck & Co., Inc. | 4-Substituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4432992A (en) | 1979-11-05 | 1984-02-21 | Merck & Co., Inc. | 4-[5(and 4)-Substituted-2-thienyl]-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4349561A (en) | 1979-11-05 | 1982-09-14 | Merck & Co., Inc. | 4-Substituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4260771A (en) | 1979-12-20 | 1981-04-07 | Merck & Co., Inc. | Interphenylene 9-thia-11-oxo-12-azaprostanoic acid compounds |
US4464363A (en) | 1979-12-20 | 1984-08-07 | Merck & Co., Inc. | Ajuvants for rectal delivery of drug substances |
US4428959A (en) | 1980-04-04 | 1984-01-31 | Merck & Co., Inc. | 4-Alkylsubstituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
US4309540A (en) | 1980-05-19 | 1982-01-05 | Merck & Co., Inc. | Substituted pyrazinyl-1,2,4-oxadiazoles |
US4362724A (en) | 1980-05-19 | 1982-12-07 | Merck & Co., Inc. | Method of treating edema and hypertension and pharmaceutical composition therefor in which the active ingredient comprises a novel substituted pyrazinyl-1,2,4-oxadiazole and a kaliuretic diuretic |
US4356314A (en) | 1980-06-30 | 1982-10-26 | Merck & Co., Inc. | [5,6,9A-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acids, their analogs, esters, salts, and derivatives |
US4317822A (en) | 1980-07-02 | 1982-03-02 | Merck & Co., Inc. | 3-Amino-5-substituted-6-halo-N-(3,4-dihydro-6-substituted-1,3,5-triazin-2-yl)2-pyrazinecarboxamides |
US4272537A (en) | 1980-07-02 | 1981-06-09 | Merck & Co., Inc. | 3-Amino-5-substituted-6-halo-N-(4,4-disubstituted-6-substituted-1,3,5-triazin-2-yl)-2-pyrazinecarboxamides |
US4277602A (en) | 1980-07-02 | 1981-07-07 | Merck & Co., Inc. | 3-Amino-5-substituted-6-halo-N-(3,4-dihydro-6-substituted-1,3,5-truazin-2-yl)2-pyrazinecarboxamides |
US4465850A (en) | 1980-09-02 | 1984-08-14 | Merck & Co., Inc. | Treatment of brain injury due to gray matter edema with (indanyloxy) butanoic acids |
US4389417A (en) | 1980-09-05 | 1983-06-21 | Merck & Co., Inc. | Treatment of gray matter edema |
US4312860A (en) | 1980-10-24 | 1982-01-26 | Regents Of The University Of California | Lung surfactant compositions |
US4394385A (en) | 1980-11-21 | 1983-07-19 | Merck & Co., Inc. | Treatment of gray matter edema |
US4316043A (en) | 1980-12-19 | 1982-02-16 | Merck & Co., Inc. | [(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acids and their analogs, esters, salts and derivatives |
US4336397A (en) | 1980-12-29 | 1982-06-22 | Merck & Co., Inc. | 2,4-Dioxo-4-substituted-1-butanoic acid derivatives useful in treating urinary tract calcium oxalate lithiasis |
US4431652A (en) | 1980-12-29 | 1984-02-14 | Merck & Co., Inc. | 4-Hydroxy-5-substituted-3(2H)-isothiazolone-1,1-dioxide derivatives useful in treating urinary tract calcium oxalate lithiasis |
US4428956A (en) | 1980-12-29 | 1984-01-31 | Merck & Co., Inc. | 4-Hydroxy-5-substituted-3-(2H)-isothiazolone-1,1-dioxide derivatives useful in treating urinary tract calcium oxalate lithiasis |
US4337258A (en) | 1980-12-29 | 1982-06-29 | Merck & Co., Inc. | 2,4-Dioxo-4-substituted-1-butanoic acid derivatives useful in treating urinary tract calcium oxalate lithiasis |
GB2112151B (en) | 1981-01-09 | 1984-10-03 | Plant Energy Syst | Excess gas flow detectors |
US4778897A (en) | 1981-02-25 | 1988-10-18 | Merck & Co., Inc. | 6H-dibenz[b,e][1,4]oxathiepin compounds |
US4582842A (en) | 1981-02-25 | 1986-04-15 | Merck & Co., Inc. | Anti-asthmatic 6H-dibenz-[b,e] [1,4]oxathiepin derivatives, compositions, and method of use therefor |
US4454132A (en) | 1981-03-16 | 1984-06-12 | Merck & Co., Inc. | Pharmaceutical compositions of novel substituted pyrazinyl-1,2,4-oxadiazoles useful in the treatment of edema and hypertension |
US4510322A (en) | 1981-07-13 | 1985-04-09 | Merck & Co., Inc. | Indacrinone having enhanced uricosuric |
US4420615A (en) | 1981-08-24 | 1983-12-13 | Merck & Co., Inc. | Substituted pyridopyrimidines as gastric secretion inhibitors |
US4463208A (en) | 1981-12-30 | 1984-07-31 | Merck & Co., Inc. | Treatment of gray matter edema |
US4425337A (en) | 1981-12-30 | 1984-01-10 | Merck & Co., Inc. | Adjuvants for rectal delivery of drug |
US4952582A (en) | 1982-01-04 | 1990-08-28 | Beyer Jr Karl H | Pyrazinoylguanidine and derivatives thereof having few polar substituents and being useful as hyperuretic agents |
US4594349A (en) | 1982-01-04 | 1986-06-10 | Beyer Jr Karl H | Hyperuretic agents |
US4663322A (en) | 1982-01-04 | 1987-05-05 | Beyer Jr Karl H | Antihypertensive hyperuretic and saluretic agent combinations |
US4389393A (en) | 1982-03-26 | 1983-06-21 | Forest Laboratories, Inc. | Sustained release therapeutic compositions based on high molecular weight hydroxypropylmethylcellulose |
US4440740A (en) | 1982-04-26 | 1984-04-03 | Merck & Co., Inc. | α-Keto aldehydes as enhancing agents of gastro-intestinal drug absorption |
US4479932A (en) | 1982-05-18 | 1984-10-30 | University Of Florida | Brain-specific drug delivery |
US4540564A (en) | 1982-05-18 | 1985-09-10 | University Of Florida | Brain-specific drug delivery |
US4501729A (en) | 1982-12-13 | 1985-02-26 | Research Corporation | Aerosolized amiloride treatment of retained pulmonary secretions |
JPS6032714A (ja) | 1983-08-01 | 1985-02-19 | Teijin Ltd | 鼻腔粘膜に適用するための安定化された粉末状薬学的組成物 |
US4699917A (en) | 1983-09-26 | 1987-10-13 | Merck & Co., Inc. | Anti-asthmatic tetrazolyl 6H-dibenz-[B,E]-[1,4]-oxathiepin derivatives, compositions, and method of use therefor |
US4604403A (en) | 1984-05-01 | 1986-08-05 | Merck & Co., Inc. | Use of substituted-3(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-1H-pyrrole-2,5-diones for treating grey matter edema |
US4605664A (en) | 1984-05-01 | 1986-08-12 | Merck & Co., Inc. | Use of substituted-3-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-1H-pyrrole-2,5-diones for treatment of grey matter edema |
US4596821A (en) | 1984-05-01 | 1986-06-24 | Merck & Co., Inc. | Treatment of gray matter edema with 3-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-1H-pyrrole-2,5-diones |
US4605663A (en) | 1984-05-01 | 1986-08-12 | Merck & Co., Inc. | Use of substituted-3-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-1H-pyrrole-2,5-diones, for treatment of grey matter edema |
US4634717A (en) | 1984-05-01 | 1987-01-06 | Merck & Co., Inc. | Substituted-3-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-1H-pyrrole-2,5-diones, useful for treating persons with gray matter edema |
US4680414A (en) | 1984-05-01 | 1987-07-14 | Merck & Co., Inc. | Substituted-3-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-1H-pyrrole-2,5-diones |
US4604394A (en) | 1984-10-01 | 1986-08-05 | Merck & Co., Inc. | Antiarrhythmic compositions and method |
US4805811A (en) | 1985-03-29 | 1989-02-21 | Aktiebolaget Draco | Dosage device |
US4754061A (en) | 1985-06-04 | 1988-06-28 | Merck & Co., Inc. | Substituted (2,3-dihydro-1-oxo-1H-inden-5-yl)alkanoic acids, their derivatives and their salts |
US4579869A (en) | 1985-08-02 | 1986-04-01 | Merck & Co., Inc. | Substituted [(2,3-dihydro-1-oxo-1H-inden-5-yl)amino]alkanoic acids, their derivatives and their salts |
US4604396A (en) | 1985-09-26 | 1986-08-05 | Merck & Co., Inc. | [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]ethanimidamides and [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]ethanimidic acid hydrazides, their derivatives and their salts |
US4654365A (en) | 1985-09-26 | 1987-03-31 | Merck & Co., Inc. | 2,3-dihydro-5-(3-oxo-2-cyclohexen-1-yl)-2-benzofurancarboxylic acids, and their salts useful in the treatment of brain injury |
US4719310A (en) | 1985-12-23 | 1988-01-12 | Merck & Co., Inc. | Ester and amide substituted (2,3-dihydro-4-(3-oxo-1-cyclohexen-1-yl)phenoxy)alkanoic acids and their salts |
US4625047A (en) | 1985-12-23 | 1986-11-25 | Merck & Co., Inc. | Substituted (2,3-dihydro-4-(3-oxo-1-cyclohexen-1-yl)phenoxy) alkanoic acids, their derivatives and their salts |
US4835313A (en) | 1986-03-03 | 1989-05-30 | Merck & Co., Inc. | (5,6-dichloro-3-oxo-9α-propyl-2,3,9,9α-tetrahydrofluoren-7-yl) alkanimidamides |
US4777281A (en) | 1986-03-03 | 1988-10-11 | Merck & Co., Inc. | [3,4-dichloro-6,7,8,8a,9,10-hexahydro-6-oxo-8a-substituted-2-phenanthrenyl)oxy]-alkanoic acids and -ethanimidamides |
US4731472A (en) | 1986-03-03 | 1988-03-15 | Merck & Co., Inc. | (5,6-dichloro-3-oxo-9A-propyl-2,3,9,9A-tetrahydrofluoren-7-yl)alkanoic acids and alkanimidamides |
US4731381A (en) | 1986-04-04 | 1988-03-15 | Merck & Co., Inc. | Method of treating a person for sickle cell anemia |
US4699926A (en) | 1986-04-04 | 1987-10-13 | Merck & Co., Inc. | Compounds useful in treating sickle cell anemia |
US4731473A (en) | 1986-04-04 | 1988-03-15 | Merck & Co., Inc. | Compounds useful in treating sickle cell anemia |
US4751244A (en) | 1986-04-04 | 1988-06-14 | Merck & Co., Inc. | Compounds useful in treating sickle cell anemia |
US4675341A (en) | 1986-08-13 | 1987-06-23 | Merck & Co., Inc. | [(5,6-dichloro-3-oxo-9a-propyl-2,3,9,9a-tetrahydrofluoren-7-yl)oxy]ethanol and its derivatives |
US4937232A (en) | 1986-09-15 | 1990-06-26 | Duke University | Inhibition of protein kinase C by long-chain bases |
US4769370A (en) | 1986-09-24 | 1988-09-06 | Merck & Co., Inc. | (1,2-dichloro-8-oxo-5a-substituted-5a,6,7,8-tetrahydrodibenzofuran-3-yl)alkanoic acids and alkanimidamides |
US4797391A (en) | 1986-09-24 | 1989-01-10 | Merck & Co., Inc. | ((5,6-dichloro-3-oxo-9,9a-disubstituted-2,3,9,9a-tetrahydrofluoren-7-yl)oxy)alkanoic acids and alkanimidamides |
US4731471A (en) | 1986-11-03 | 1988-03-15 | Merck & Co., Inc. | (5,6-dichloro-3-oxo-2,3,9,9a-tetrahydrofluoren-7-yl)-alkanoic acids and alkanimidamides bearing novel functional 9a-substituents |
US4731470A (en) | 1986-11-03 | 1988-03-15 | Merck & Co., Inc. | [(5,6-dichloro-3-oxo-2,9a-alkano-2,3,9,9a-tetrahydro-1H-fluoren-7-yl)oxy]alkanoic acids and alkanimidamides |
US4782073A (en) | 1986-12-24 | 1988-11-01 | Merck & Co., Inc. | Amides of [(5,6-dichloro-3-oxo-9-alpha-substituted-2,3,9,9-alpha-tetrahydrofluoren-7-yl-oxyl]acetic acids, and pharmaceutical compositions thereof |
US4775695A (en) | 1987-06-01 | 1988-10-04 | Merck & Co., Inc. | Substituted amidinoalkoxy and amidinoalkylamino indanones and salts thereof |
US4771076A (en) | 1987-06-01 | 1988-09-13 | Merck & Co., Inc. | [(2-substituted 1,2-dihydro-1-oxo-1H-inden-5-yl)oxy]alkanesulfonic acids and salts thereof |
US5132296A (en) | 1987-08-14 | 1992-07-21 | Cherksey Bruce D | Membrane NA+ channel protein and related therapeutic compounds |
US5242947A (en) | 1988-02-10 | 1993-09-07 | New York University | Use of polyamines as ionic-channel regulating agents |
US4894376A (en) | 1988-02-26 | 1990-01-16 | Trustees Of The University Of Pennsylvania | Methods of treating diseases characterized by hyperexcitability of neurons |
US4923874A (en) | 1988-07-21 | 1990-05-08 | G. D. Searle & Co. | Use of 8-azapurin-6-one derivatives for control of hypertension |
US5100806A (en) | 1989-03-24 | 1992-03-31 | Macri James N | Method for detecting Edwards syndrome |
US4955371A (en) | 1989-05-08 | 1990-09-11 | Transtech Scientific, Inc. | Disposable inhalation activated, aerosol device for pulmonary medicine |
CA2063273C (en) | 1989-07-11 | 2002-09-24 | Bradley J. Benson | Surfactant compositions and methods |
US5707644A (en) | 1989-11-04 | 1998-01-13 | Danbiosyst Uk Limited | Small particle compositions for intranasal drug delivery |
US5215991A (en) | 1990-01-26 | 1993-06-01 | Allergan, Inc. | Combination of selective alpha-adrenergic agonists and Na+ /H+ ex |
DE4003272A1 (de) | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | Neue treibgasmischungen und ihre verwendung in arzneimittelzubereitungen |
US5449682A (en) | 1990-02-13 | 1995-09-12 | Merck & Co., Inc. | Angiotensin II antagonists incorporating a substituted benzyl element |
US5182299A (en) | 1990-03-19 | 1993-01-26 | Brigham And Women's Hospital | Treatment of osmotic disturbance with organic osmolytes |
WO1992005779A1 (en) | 1990-10-05 | 1992-04-16 | The University Of North Carolina At Chapel Hill | Method of administering amiloride |
US5614216A (en) | 1990-10-17 | 1997-03-25 | The Liposome Company, Inc. | Synthetic lung surfactant |
EP0517573A1 (fr) | 1991-06-05 | 1992-12-09 | Synthelabo | Compositions pharmaceutiques pour le traitement des affections des voies respiratoires |
US5292498A (en) | 1991-06-19 | 1994-03-08 | The University Of North Carolina At Chapel Hill | Method of treating lung disease with uridine triphosphates |
KR100246082B1 (ko) | 1991-07-02 | 2000-04-01 | 인헤일, 인코오포레이티드 | 에어로졸화된약제를전달하는방법및장치 |
DE69232034T2 (de) | 1991-12-18 | 2002-06-06 | Minnesota Mining And Mfg. Co., Saint Paul | Aerosolzusammensetzungen für Arzneimittelsuspensionen |
US7105152B1 (en) | 1991-12-18 | 2006-09-12 | 3M Innovative Properties Company | Suspension aerosol formulations |
US5261538A (en) | 1992-04-21 | 1993-11-16 | Glaxo Inc. | Aerosol testing method |
US5312820A (en) | 1992-07-17 | 1994-05-17 | Merck & Co., Inc. | Substituted carbamoyl and oxycarbonyl derivatives of biphenylmethylamines |
DE4236237A1 (de) | 1992-10-27 | 1994-04-28 | Behringwerke Ag | Prodrugs, ihre Herstellung und Verwendung als Arzneimittel |
EP0612723B1 (de) | 1993-02-20 | 1997-08-27 | Hoechst Aktiengesellschaft | Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, als Inhibitoren des zellulären Na+/H+-Austauschs oder als Diagnostikum sowie sie enthaltendes Medikament |
US5384128A (en) | 1993-03-02 | 1995-01-24 | University Of Alabama Research Foundation | Method of and compounds for treatment for cystic fibrosis |
US5512269A (en) | 1993-06-09 | 1996-04-30 | Burroughs Wellcome, Co. | Method of treating retained pulmonary secretions |
US6051576A (en) | 1994-01-28 | 2000-04-18 | University Of Kentucky Research Foundation | Means to achieve sustained release of synergistic drugs by conjugation |
AUPM411494A0 (en) | 1994-02-25 | 1994-03-24 | Central Sydney Area Health Service | Method and device for the provocation of upper or lower airway narrowing and/or the induction of sputum |
US6190691B1 (en) | 1994-04-12 | 2001-02-20 | Adolor Corporation | Methods for treating inflammatory conditions |
US5962477A (en) | 1994-04-12 | 1999-10-05 | Adolor Corporation | Screening methods for cytokine inhibitors |
US5538991A (en) | 1994-09-14 | 1996-07-23 | Merck & Co., Inc. | Endothelin antagonists bearing 5-membered heterocyclic amides |
US5522385A (en) | 1994-09-27 | 1996-06-04 | Aradigm Corporation | Dynamic particle size control for aerosolized drug delivery |
US5618557A (en) | 1994-11-22 | 1997-04-08 | E.R. Squibb & Sons, Inc. | Prophylactic treatment of allergic contact dermatitis |
US5622163A (en) | 1994-11-29 | 1997-04-22 | Iep Group, Inc. | Counter for fluid dispensers |
US5544647A (en) | 1994-11-29 | 1996-08-13 | Iep Group, Inc. | Metered dose inhalator |
US5656256A (en) | 1994-12-14 | 1997-08-12 | The University Of North Carolina At Chapel Hill | Methods of treating lung disease by an aerosol containing benzamil or phenamil |
EP1166811B1 (en) | 1995-04-14 | 2006-12-06 | SmithKline Beecham Corporation | Metered dose inhaler for fluticasone propionate |
US5908611A (en) | 1995-05-05 | 1999-06-01 | The Scripps Research Institute | Treatment of viscous mucous-associated diseases |
US5635160A (en) | 1995-06-07 | 1997-06-03 | The University Of North Carolina At Chapel Hill | Dinucleotides useful for the treatment of cystic fibrosis and for hydrating mucus secretions |
US5994336A (en) | 1995-06-07 | 1999-11-30 | Magainin Pharmaceuticals Inc. | Method of inhibiting proliferation of cells by administering an aminosterol compound |
US5628984A (en) | 1995-07-31 | 1997-05-13 | University Of North Carolina At Chapel Hill | Method of detecting lung disease |
AU7157896A (en) | 1995-09-12 | 1997-04-01 | Children's Hospital Medical Center Of Northern California | Cystic fibrosis therapy |
US6399585B1 (en) | 1996-05-15 | 2002-06-04 | Janet E. Larson | In Utero treatment of CFTR-related deficiencies |
US6015828A (en) | 1996-05-31 | 2000-01-18 | Cuppoletti; John | Chemical modification of chloride channels as a treatment for cystic fibrosis and other diseases |
US6071910A (en) | 1996-12-05 | 2000-06-06 | Mayo Foundation For Medical Education And Research | Use of agents to treat eosinophil-associated pathologies |
NZ337225A (en) | 1997-02-06 | 2002-03-28 | Inspire Pharmaceuticals Inc | Dinucleotides useful for treating chronic pulmonary obstructive disorder |
US7223744B2 (en) | 1997-02-10 | 2007-05-29 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof |
US6818629B2 (en) | 1997-02-10 | 2004-11-16 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising P1-(2'-deoxycytidine 5'-)P4-(uridine 5'-) tetraphosphate |
US20010031244A1 (en) | 1997-06-13 | 2001-10-18 | Chiesi Farmaceutici S.P.A. | Pharmaceutical aerosol composition |
ZA987847B (en) | 1997-08-29 | 1999-06-28 | Univ North Carolina | Method of treating lung diseases with uridine 5'-diphosphate and analogs thereof |
US6153187A (en) | 1997-09-02 | 2000-11-28 | Insight Strategy & Marketing Ltd. | Use of glycosaminoglycans degrading enzymes for management of airway associated diseases |
US6159968A (en) | 1998-01-15 | 2000-12-12 | University Of Cincinnati | Activation of chloride channels for correction of defective chloride transport |
US6291514B1 (en) | 1998-02-09 | 2001-09-18 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines, preparation thereof, and use thereof as protease inhibitors |
GB9807232D0 (en) | 1998-04-03 | 1998-06-03 | Univ Cardiff | Aerosol composition |
CA2332540A1 (en) | 1998-05-22 | 1999-12-02 | Benjamin R. Yerxa | Therapeutic dinucleotide and derivatives |
US6294188B1 (en) | 1998-07-09 | 2001-09-25 | Aviana Biopharm Inc. | Methods involving changing the constitutive and stimulated secretions of the local reproductive system of women |
US6475467B1 (en) | 1998-08-04 | 2002-11-05 | Jago Research Ag | Medicinal aerosol formulations |
US6458338B1 (en) | 1998-09-22 | 2002-10-01 | Aeropharm Technology Incorporated | Amino acid stabilized medicinal aerosol formulations |
US6136294C1 (en) | 1998-09-22 | 2002-09-24 | Aeropharm Technology Inc | Amino acid stabilized medical aerosol formulation |
WO2000023023A1 (en) | 1998-10-20 | 2000-04-27 | The University Of North Carolina At Chapel Hill | Methods of hydrating mucosal surfaces |
CA2348529A1 (en) | 1998-10-27 | 2000-05-04 | Yale University | Conductance of improperly folded proteins through the secretory pathway |
US6926911B1 (en) | 1998-12-22 | 2005-08-09 | The University Of North Carolina At Chapel Hill | Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs |
US6329034B1 (en) | 1999-01-18 | 2001-12-11 | Roger L. Pendry | Label having tab member and methods for forming, applying and using the same |
US6116234A (en) | 1999-02-01 | 2000-09-12 | Iep Pharmaceutical Devices Inc. | Metered dose inhaler agitator |
AR023088A1 (es) | 1999-02-26 | 2002-09-04 | Inspire Pharmaceuticals Inc | Uso de disfosfatos de uridina, adenina y citidina y analogos de los mismos para la manufactura de un medicamento para la estimulacion de la hidratacion delas mucosas. |
BR0011343A (pt) | 1999-06-05 | 2002-03-12 | Innovata Biomed Ltd | Dispositivo de distribuição de medicamento,e,métodos de administrar um medicamento por inalação,e de,tratamento de um paciente com distúrbio respiratório |
GB2353222B (en) | 1999-06-23 | 2001-09-19 | Cambridge Consultants | Inhalers |
US20040195160A1 (en) | 1999-07-12 | 2004-10-07 | Marine Desalination Systems, L.L.C. | Hydrate-based reduction of fluid inventories and concentration of aqueous and other water-containing products |
AU774865B2 (en) | 1999-07-19 | 2004-07-08 | University Of North Carolina At Chapel Hill, The | Conjugates of sodium channel blockers and methods of using the same |
GB9920839D0 (en) | 1999-09-04 | 1999-11-10 | Innovata Biomed Ltd | Inhaler |
ES2225246T3 (es) | 1999-10-12 | 2005-03-16 | Shl Medical Ab | Inhalador. |
US6297226B1 (en) | 1999-10-15 | 2001-10-02 | Neotherapeutics, Inc. | Synthesis and methods of use of 9-substituted guanine derivatives |
AUPQ344799A0 (en) | 1999-10-15 | 1999-11-11 | University Of Sydney, The | Treatment of respiratory diseases and infections |
JO2178B1 (en) | 1999-10-19 | 2003-04-23 | اف . هوفمان لاروش ايه جي | Treatment of invasive diseases, using selected anti-PAR materials |
ATE461692T1 (de) | 1999-10-29 | 2010-04-15 | Novartis Ag | Trockenpulverzusammensetzungen mit verbesserter dispersität |
US6204270B1 (en) | 1999-11-12 | 2001-03-20 | Eyal S. Ron | Ophthalmic and mucosal preparations |
GB9928265D0 (en) | 1999-12-01 | 2000-01-26 | Innovata Biomed Ltd | Inhaler |
US6476048B1 (en) | 1999-12-07 | 2002-11-05 | Inotek Pharamaceuticals Corporation | Substituted phenanthridinones and methods of use thereof |
SE9904706D0 (sv) | 1999-12-21 | 1999-12-21 | Astra Ab | An inhalation device |
WO2001055390A1 (en) | 2000-01-28 | 2001-08-02 | Human Genome Sciences, Inc. | Human serpin polynucleotides, polypeptides, and antibodies |
US7345051B2 (en) | 2000-01-31 | 2008-03-18 | Genaera Corporation | Mucin synthesis inhibitors |
US7171965B2 (en) | 2000-02-01 | 2007-02-06 | Valois S.A.S. | Breath actuated dry powder inhaler and tape dose strip |
US20040199456A1 (en) | 2000-08-01 | 2004-10-07 | Andrew Flint | Method and apparatus for explaining credit scores |
FR2813593B1 (fr) | 2000-09-07 | 2002-12-06 | Valois Sa | Dispositif de distribution de produit fluide de type multidose |
GB0026647D0 (en) | 2000-10-31 | 2000-12-13 | Glaxo Group Ltd | Medicament dispenser |
DE60139021D1 (de) * | 2000-11-20 | 2009-07-30 | Biovitrum Ab Publ | Piperazinylpyrazinverbindungen als antagonisten des serotonin-5-ht2-rezeptors |
DE10101440B4 (de) | 2001-01-15 | 2017-10-26 | REMS-WERK Christian Föll und Söhne GmbH & Co. | Preßzange |
GB2377532B (en) | 2001-07-11 | 2005-06-29 | Sendo Int Ltd | Communications devices operable to electronically process text data for representing characters of a text message, and methods for operating such devices |
US20030135716A1 (en) | 2002-01-14 | 2003-07-17 | Gil Vinitzky | Method of creating a high performance virtual multiprocessor by adding a new dimension to a processor's pipeline |
US6858614B2 (en) | 2002-02-19 | 2005-02-22 | Parion Sciences, Inc. | Phenolic guanidine sodium channel blockers |
US6858615B2 (en) * | 2002-02-19 | 2005-02-22 | Parion Sciences, Inc. | Phenyl guanidine sodium channel blockers |
US6889690B2 (en) | 2002-05-10 | 2005-05-10 | Oriel Therapeutics, Inc. | Dry powder inhalers, related blister devices, and associated methods of dispensing dry powder substances and fabricating blister packages |
ATE548354T1 (de) | 2002-07-24 | 2012-03-15 | Ptc Therapeutics Inc | Ureido-substituierte benzoesäureverbindungen und ihre verwendung für die nonsense-suppression und behandlung von erkrankungen |
US20050227974A9 (en) | 2002-08-01 | 2005-10-13 | Euro-Celtique S.A. | Aminoalkyl-substituted aryl compounds and their use as sodium channel blockers |
US6903105B2 (en) | 2003-02-19 | 2005-06-07 | Parion Sciences, Inc. | Sodium channel blockers |
HUE055434T2 (hu) | 2003-04-11 | 2021-11-29 | Ptc Therapeutics Inc | 1,2,4-Oxadiazol-benzoesav vegyület és alkalmazása nonszensz szupresszióra és betegség kezelésére |
EP1488819A1 (en) | 2003-06-16 | 2004-12-22 | Rijksuniversiteit te Groningen | Dry powder inhaler and method for pulmonary inhalation of dry powder |
CA2534682C (en) | 2003-08-18 | 2013-02-26 | Parion Sciences, Inc. | Capped pyrazinoylguanidine sodium channel blockers |
US7317013B2 (en) | 2003-08-18 | 2008-01-08 | Parion Sciences, Inc. | Cyclic pyrazinoylguanidine sodium channel blockers |
CA2534568A1 (en) | 2003-08-18 | 2005-03-24 | Parion Sciences, Inc. | Aliphatic pyrazinoylguanidine sodium channel blockers |
US20050090505A1 (en) | 2003-08-18 | 2005-04-28 | Johnson Michael R. | Methods of reducing risk of infection from pathogens |
US20090253714A1 (en) | 2003-08-20 | 2009-10-08 | Johnson Michael R | Methods of reducing risk of infection from pathogens |
US7745442B2 (en) * | 2003-08-20 | 2010-06-29 | Parion Sciences, Inc. | Methods of reducing risk of infection from pathogens |
DE10339710A1 (de) | 2003-08-22 | 2005-03-17 | Siemens Ag | Verfahren zur Zulassungsanfrage zu einem Datenzugriff auf Nutzungs- und Zustandsdaten von Mobilfunkteilnehmern in einem Mobilfunknetz |
US7499570B2 (en) | 2004-03-02 | 2009-03-03 | Siemens Corporate Research, Inc. | Illumination invariant change detection |
US6887597B1 (en) | 2004-05-03 | 2005-05-03 | Prestone Products Corporation | Methods and composition for cleaning and passivating fuel cell systems |
US8354427B2 (en) | 2004-06-24 | 2013-01-15 | Vertex Pharmaceutical Incorporated | Modulators of ATP-binding cassette transporters |
US7375102B2 (en) | 2004-06-28 | 2008-05-20 | Amgen Sf, Llc | Tetrahydroquinazolin-4(3H)-one-related and tetrahydropyrido[2,3-D]pyrimidin-4(3H)-one-related compounds, compositions and methods for their use |
KR20070052317A (ko) | 2004-08-18 | 2007-05-21 | 마이클 알 존슨. | 환형 아미드 및 에스테르 피라지노일구아니딘 나트륨 채널차단제 |
US7399766B2 (en) | 2004-08-18 | 2008-07-15 | Parion Sciences, Inc. | Soluble amide & ester pyrazinoylguanidine sodium channel blockers |
US20090324724A1 (en) | 2004-08-18 | 2009-12-31 | Parion Sciences, Inc. | Soluble amide & ester pyrazinoylguanidine sodium channel blockers |
US7956059B2 (en) | 2004-08-18 | 2011-06-07 | Parion Sciences, Inc. | Aliphatic amide and ester pyrazinoylguanidine sodium channel blockers |
BRPI0515995A (pt) | 2004-10-13 | 2008-08-19 | Ptc Therapeutics Inc | compostos para supressão sem sentido, e métodos para sua aplicação |
JP2009221164A (ja) | 2008-03-17 | 2009-10-01 | Nitto Denko Corp | 肺線維症処置剤 |
AU2006203934B2 (en) | 2005-01-07 | 2010-09-09 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of RSV and therapeutic uses thereof |
JP4964469B2 (ja) | 2005-01-14 | 2012-06-27 | ガジック・テクニカル・エンタープライゼス | 磁気ヘッド及びディスクをテストするための真空チャック・スピンスタンド |
US20070021439A1 (en) | 2005-07-25 | 2007-01-25 | Parion Sciences, Inc. | Methods of reducing risk of infection from pathogens with soluble amide and ester pyrazinoylguanidine sodium channel blockers |
US7807834B2 (en) | 2005-08-03 | 2010-10-05 | Parion Sciences, Inc. | Capped pyrazinoylguanidine sodium channel blockers |
US20090306009A1 (en) | 2005-12-06 | 2009-12-10 | P2-Science Aps | Modulation of the P2Y2 Receptor Pathway |
GB0526240D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
GB0526244D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
AU2006331565A1 (en) | 2005-12-27 | 2007-07-05 | Vertex Pharmaceuticals Incorporated | Compounds useful in CFTR assays and methods therewith |
KR20150001844A (ko) | 2006-01-24 | 2015-01-06 | 넥스바이오, 인코퍼레이티드 | 고분자 미소 구체들의 조제를 위한 기술 |
US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
ES2377840T3 (es) | 2006-05-12 | 2012-04-02 | Vertex Pharmaceuticals, Inc. | Composiciones de N-[2,4-bis(1,1-dimetiletil)-5-hidroxifenil]-1,4-dihidro-4-oxoquinolina-3-carboxamida |
US20110195973A1 (en) | 2006-06-09 | 2011-08-11 | Parion Sciences, Inc. | Cyclic substituted pyrazinoylguanidine sodium channel blockers possessing beta agonist activity |
JP5254961B2 (ja) * | 2006-06-09 | 2013-08-07 | パリオン・サイエンシィズ・インコーポレーテッド | ベータアゴニスト活性を有するフェニル置換ピラジノイルグアニジンナトリウムチャネル遮断薬 |
WO2007146867A2 (en) | 2006-06-09 | 2007-12-21 | Parion Sciences Inc. | Aliphatic pyrazinoylguanidine sodium channel blockers with beta agonist activity |
MX2009002602A (es) | 2006-09-07 | 2009-05-28 | Parion Sciences Inc | Metodos para aumentar la hidratacion mucosa y el despeje mucoso mediante tratamiento con bloqueadores de canal de sodio y osmolitos. |
CN101534813A (zh) * | 2006-09-07 | 2009-09-16 | 帕里昂科学公司 | 通过使用钠通道阻断剂和渗透调节剂的治疗来增加粘膜水化和粘液清除的方法 |
AR062742A1 (es) * | 2006-09-07 | 2008-12-03 | Johnson Michael R | Hidratacion de la mucosa y depuracion de la mucosa aumentadas por tratamiento con bloquadores de canales de sodio y osmolitos |
US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
US7754739B2 (en) | 2007-05-09 | 2010-07-13 | Vertex Pharmaceuticals Incorporated | Modulators of CFTR |
US20080293740A1 (en) | 2007-04-03 | 2008-11-27 | Parion Sciences, Inc. | Method of treating acid-sensing ion channel mediated pain, cough suppression, and central nervous system disorders |
WO2008124491A1 (en) | 2007-04-03 | 2008-10-16 | Parion Sciences, Inc. | Pyrazinoylguanidine compounds for use taste modulators |
US20100215588A1 (en) | 2007-04-26 | 2010-08-26 | Rami Skaliter | Therapeutic delivery of inhibitory nucleic acid molecules to the respiratory system |
KR20100005730A (ko) | 2007-05-07 | 2010-01-15 | 노파르티스 아게 | 유기 화합물 |
EP1997502A1 (en) | 2007-06-01 | 2008-12-03 | CHIESI FARMACEUTICI S.p.A. | Reconstituted surfactants having improved properties |
WO2009015286A2 (en) | 2007-07-24 | 2009-01-29 | Nexbio, Inc. | Technology for the preparation of microparticles |
AU2008310734B2 (en) | 2007-10-10 | 2014-06-05 | Parion Sciences, Inc. | Delivering osmolytes by nasal cannula |
EP2217249A4 (en) | 2007-11-06 | 2011-10-12 | Benaroya Res Inst | INHIBITION OF VERSICANE BY ARNS AND OTHER MOLECULES |
EP2520574A1 (en) | 2007-12-10 | 2012-11-07 | Novartis AG | Amiloride analogues substituted on the cyclic guanidine moiety as ENaC blockers for treating respiratory diseases |
NZ586940A (en) | 2008-02-26 | 2012-08-31 | Parion Sciences Inc | Poly aromatic sodium channel blocker compounds comprising both pyrazine and guanidine moieties |
CA2716109C (en) | 2008-02-28 | 2016-07-19 | Vertex Pharmaceuticals Incorporated | Heteroaryl derivatives as cftr modulators |
US8261047B2 (en) | 2008-03-17 | 2012-09-04 | Freescale Semiconductor, Inc. | Qualification of conditional debug instructions based on address |
ES2442945T3 (es) | 2008-03-31 | 2014-02-14 | Vertex Pharmaceuticals Inc. | Derivados de piridilo como moduladores del CFTR |
US8664228B2 (en) | 2008-05-13 | 2014-03-04 | Novartis Ag | 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid derivatives and their use as epithelial sodium channel blockers for the treatment of airway diseases |
EP2300010B1 (en) | 2008-06-10 | 2015-03-04 | Novartis AG | Pyrazine derivatives as epithelial sodium channel blockers |
US20100074881A1 (en) | 2008-07-11 | 2010-03-25 | Parion Sciences, Inc. | Multiple nebulizer systems |
NZ592504A (en) | 2008-10-23 | 2013-04-26 | Vertex Pharma | Solid forms of n-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide |
US20100316628A1 (en) | 2008-12-09 | 2010-12-16 | The General Hospital Corporation | Agents and methods for treating respiratory disorders |
US8367660B2 (en) | 2008-12-30 | 2013-02-05 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
WO2011156355A1 (en) | 2010-06-09 | 2011-12-15 | Kainos Medicine, Inc. | Production method of phenyl guanidine salts and their intermediates |
KR20120017648A (ko) | 2010-08-19 | 2012-02-29 | 삼성전자주식회사 | 디스플레이장치와, 디스플레이 패널의 구동방법 |
AR086745A1 (es) | 2011-06-27 | 2014-01-22 | Parion Sciences Inc | 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida |
EP2723176B1 (en) | 2011-06-27 | 2017-04-12 | Parion Sciences, Inc. | A chemically and metabolically stable dipeptide possessing potent sodium channel blocker activity |
EP3366680B1 (en) | 2012-05-29 | 2020-05-13 | Parion Sciences, Inc. | Dendrimer like amino amides possessing sodium channel blocker activity for the treatment of dry eye and other mucosal diseases |
WO2014036445A2 (en) | 2012-08-31 | 2014-03-06 | Johnson Michael R | Novel mucolytic agents |
EP2928878B1 (en) | 2012-11-15 | 2016-11-02 | Bayer Pharma Aktiengesellschaft | 5-fluoro-n-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfoximine group |
DK2931713T3 (en) | 2012-12-17 | 2017-01-30 | Parion Sciences Inc | CHLORPYRAZINE CARBOXAMIDE DERIVATIVES USED FOR THE TREATMENT OF DISEASES BENEFITED BY INDEPENDENT MOSPHEREWIN |
JP6392241B2 (ja) | 2012-12-17 | 2018-09-19 | パリオン・サイエンシィズ・インコーポレーテッド | 3,5−ジアミノ−6−クロロ−n−(n−(4−フェニルブチル)カルバムイミドイル)ピラジン−2−カルボキサミド化合物 |
JP6596421B2 (ja) | 2013-08-23 | 2019-10-23 | パリオン・サイエンシィズ・インコーポレーテッド | ジチオール粘液溶解薬 |
US9102633B2 (en) | 2013-12-13 | 2015-08-11 | Parion Sciences, Inc. | Arylalkyl- and aryloxyalkyl-substituted epithelial sodium channel blocking compounds |
US20150376145A1 (en) | 2014-06-30 | 2015-12-31 | Parion Sciences, Inc. | Stable sodium channel blockers |
-
2013
- 2013-12-13 JP JP2015548005A patent/JP6392241B2/ja not_active Expired - Fee Related
- 2013-12-13 CN CN201380070785.3A patent/CN104995178B/zh not_active Expired - Fee Related
- 2013-12-13 AU AU2013363215A patent/AU2013363215B2/en not_active Ceased
- 2013-12-13 MX MX2015007797A patent/MX2015007797A/es active IP Right Grant
- 2013-12-13 CN CN201810521371.2A patent/CN108658876A/zh active Pending
- 2013-12-13 NZ NZ709197A patent/NZ709197A/en not_active IP Right Cessation
- 2013-12-13 EP EP13826678.8A patent/EP2931712B8/en not_active Not-in-force
- 2013-12-13 KR KR1020157018915A patent/KR20150095870A/ko not_active Application Discontinuation
- 2013-12-13 RU RU2018138195A patent/RU2018138195A/ru not_active Application Discontinuation
- 2013-12-13 EP EP18162918.9A patent/EP3428153A1/en not_active Withdrawn
- 2013-12-13 RU RU2015129062A patent/RU2671976C2/ru active
- 2013-12-13 WO PCT/US2013/075093 patent/WO2014099673A1/en active Application Filing
- 2013-12-13 BR BR112015014178A patent/BR112015014178A2/pt not_active Application Discontinuation
- 2013-12-13 US US14/106,098 patent/US9029382B2/en not_active Expired - Fee Related
-
2015
- 2015-01-08 US US14/592,480 patent/US9695134B2/en active Active
- 2015-06-15 IL IL239409A patent/IL239409A/en active IP Right Grant
- 2015-06-24 ZA ZA201504561A patent/ZA201504561B/en unknown
-
2017
- 2017-06-29 US US15/638,175 patent/US10246425B2/en not_active Expired - Fee Related
- 2017-08-10 IL IL253951A patent/IL253951B/en active IP Right Grant
-
2018
- 2018-05-21 AU AU2018203562A patent/AU2018203562A1/en not_active Abandoned
- 2018-08-22 JP JP2018155295A patent/JP2019001803A/ja active Pending
-
2019
- 2019-03-13 US US16/352,548 patent/US20190308943A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
US20170362187A1 (en) | 2017-12-21 |
ZA201504561B (en) | 2019-10-30 |
BR112015014178A2 (pt) | 2017-07-11 |
RU2671976C2 (ru) | 2018-11-08 |
US20190308943A1 (en) | 2019-10-10 |
AU2013363215B2 (en) | 2018-03-01 |
US9695134B2 (en) | 2017-07-04 |
CN104995178B (zh) | 2018-06-26 |
WO2014099673A1 (en) | 2014-06-26 |
US20140170244A1 (en) | 2014-06-19 |
NZ709197A (en) | 2020-06-26 |
JP6392241B2 (ja) | 2018-09-19 |
AU2013363215A1 (en) | 2015-07-02 |
CN104995178A (zh) | 2015-10-21 |
US10246425B2 (en) | 2019-04-02 |
CN108658876A (zh) | 2018-10-16 |
JP2016503027A (ja) | 2016-02-01 |
MX2015007797A (es) | 2015-10-05 |
JP2019001803A (ja) | 2019-01-10 |
IL253951B (en) | 2019-08-29 |
EP2931712B1 (en) | 2018-03-21 |
RU2015129062A (ru) | 2017-01-23 |
IL253951A0 (en) | 2017-10-31 |
EP2931712B8 (en) | 2018-05-23 |
EP2931712A1 (en) | 2015-10-21 |
US20150299142A1 (en) | 2015-10-22 |
KR20150095870A (ko) | 2015-08-21 |
IL239409A0 (en) | 2015-07-30 |
IL239409A (en) | 2017-08-31 |
AU2018203562A1 (en) | 2018-06-07 |
US9029382B2 (en) | 2015-05-12 |
EP3428153A1 (en) | 2019-01-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2018138195A (ru) | Соединения 3,5-диамино-6-хлор-n-(n-(4- фенилбутил)карбамимидоил)пиразин-2-карбоксамида | |
RU2015129065A (ru) | Производные хлор-пиразинкарбоксамида, обладающие активностью блокирования эпителиальных натриевых каналов | |
JP2014518268A5 (ru) | ||
HRP20151346T1 (hr) | 3,5-diamino-6-klor-n-(n-(4-(4-(2-(heksil(2,3,4,5,6-pentahidroksiheksil)amino)etoksi)fenil)butil)karbamimidoil)pirazin-2-karboksamid | |
RU2019100425A (ru) | Новая доза и препаративная форма | |
RU2013142268A (ru) | Фармацевтическая композиция | |
JP2018199684A5 (ru) | ||
JP2019528320A5 (ru) | ||
TW200817343A (en) | Method of enhancing mucosal hydration and mucosal clearance by treatment with sodium channel blockers and osmolytes | |
NZ585856A (en) | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease | |
JP2013531056A5 (ru) | ||
TW200819430A (en) | Enhanced mucosal hydration and mucosal clearance by treatment with sodium channel blockers and osmolytes | |
RU2015129076A (ru) | Арилалкил- и арилоксиалкил-замещенные соединения, блокирующие эпителиальный натриевый канал | |
RU2013119938A (ru) | Фармацевтическая композиция | |
RU2013104401A (ru) | Фармацевтический препарат, содержащий ингибитор фосфодиэстеразы | |
AU2018230805A2 (en) | Antimicrobial compounds, compositions, and uses thereof | |
UA119774C2 (uk) | Комбінації формотеролу і будесоніду для лікування хронічної обструктивної хвороби легень (хохл) | |
ES2862799T3 (es) | Tosilato de suplatast para tratar la tos asociada con neumopatía intersticial | |
WO2015014209A1 (zh) | 稳定渗透压的丙酮酸药物组成及其在健康人和肺病病人中的排毒作用 | |
AR039409A1 (es) | Composicion farmaceutica en polvo seco para inhalacion, fabricacion y uso. | |
AU2018262108A1 (en) | Compounds for the treatment of respiratory diseases | |
RU2010120806A (ru) | Композиции для ингаляции, содержащие кислоту монтелукаст и ингибитор pde-4 или ингаляционный кортикостероид | |
JP2019505596A5 (ru) | ||
RU2012116226A (ru) | Бронхолитическое средство на основе простагландина | |
CA3211907A1 (en) | New peptide conjugates |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FA93 | Acknowledgement of application withdrawn (no request for examination) |
Effective date: 20161214 |