RU2016138746A - Циклогексанкарбоксамид с охлаждающими свойствами - Google Patents

Циклогексанкарбоксамид с охлаждающими свойствами Download PDF

Info

Publication number
RU2016138746A
RU2016138746A RU2016138746A RU2016138746A RU2016138746A RU 2016138746 A RU2016138746 A RU 2016138746A RU 2016138746 A RU2016138746 A RU 2016138746A RU 2016138746 A RU2016138746 A RU 2016138746A RU 2016138746 A RU2016138746 A RU 2016138746A
Authority
RU
Russia
Prior art keywords
compound
concentration
aryl
opo
aliphatic
Prior art date
Application number
RU2016138746A
Other languages
English (en)
Other versions
RU2016138746A3 (ru
Inventor
Джон Кристиан ХОТ
Майкл РЕЙЛИ
Стивен Гамильтон ХОУК
Цинсинь ЛЭЙ
Якан ЛИН
Лоуелл Алан САНКЕР
Коти Татачар СРИКРИШНА
Original Assignee
Дзе Проктер Энд Гэмбл Компани
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Дзе Проктер Энд Гэмбл Компани filed Critical Дзе Проктер Энд Гэмбл Компани
Publication of RU2016138746A3 publication Critical patent/RU2016138746A3/ru
Publication of RU2016138746A publication Critical patent/RU2016138746A/ru

Links

Classifications

    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/10—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/0043—Nose
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q9/00—Preparations for removing hair or for aiding hair removal
    • A61Q9/02—Shaving preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/68—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/73—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/75—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
    • C07C255/44—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms at least one of the singly-bound nitrogen atoms being acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/31—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/33—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/24—Thermal properties
    • A61K2800/244—Endothermic; Cooling; Cooling sensation

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Birds (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Inorganic Chemistry (AREA)
  • Otolaryngology (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • Dispersion Chemistry (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Fats And Perfumes (AREA)
  • Confectionery (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Thermotherapy And Cooling Therapy Devices (AREA)
  • Medicinal Preparation (AREA)

Claims (76)

1. Соединение, имеющее следующую структуру:
Figure 00000001
R1 выбран из Н, алкила, аминоалкила, алкокси;
Q=Н2, О, -OR1, -N(R1)2, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
V=NR1, O, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
W=H2, O;
X, Y = независимо выбраны из H, арила, нафтила для n=0;
X, Y = алифатическая СН2 или ароматическая СН для n≥1 и Z выбран из алифатической СН2, ароматической СН или гетероатома;
A = низший алкокси, низший алкилтио, арил, замещенный арил или конденсированный арил; и
стереохимия является переменной в положениях, отмеченных *.
2. Соединение по п. 1, при этом соединение активирует, по меньшей мере, один из TRPA1, TRPV1 или TRPM8.
3. Соединение по п. 2, при этом соединение при концентрации приблизительно 5,2⋅10-5% обеспечивает: а) большую активацию TRPM8, чем WS5 (N-этоксикарбонилметил-п-ментан-3-карбоксамид) при концентрации приблизительно 30 мМ; b) большую активацию TRPA1, чем аллилизотиоцианат при концентрации приблизительно 50 мМ; и с) большую активацию TRPV1, чем капсаицин при концентрации приблизительно 350 нМ.
4. Соединение по п. 2, при этом соединение при концентрации приблизительно 5,2⋅10-5% обеспечивает:
a) по меньшей мере, приблизительно 110% активацию TRPM8 по сравнению с WS5 при концентрации приблизительно 30 мМ;
b) по меньшей мере, приблизительно 180% активацию TRPA1 по сравнению с аллилизотиоцианатом при концентрации приблизительно 50 мМ; и
с) по меньшей мере, приблизительно 100% активацию TRPV1 по сравнению с капсаицином при концентрации приблизительно 350 нМ.
5. Соединение по п. 2, при этом активацию определяют путем измерения количеств внутриклеточного кальция.
6. Соединение по п. 5, при этом измерение количеств внутриклеточного кальция выполняют при помощи флуоресцентного красителя.
7. Соединение по п. 2, при этом соединение при концентрации приблизительно 5,2⋅10-5% обеспечивает большую активацию TRPM8, чем WS5 при концентрации приблизительно 30 мМ.
8. Композиция для личной гигиены, содержащая соединение по п. 1.
9. Изомерная ВЭЖХ фракция соединения по п. 1, при этом изомерная ВЭЖХ фракция при концентрации приблизительно 12,2 нМ характеризуется более высокой активацией TRPM8 через 10 минут сравнительно с WS5 при концентрации приблизительно 10 мкм.
10. Композиция, содержащая соединение по п. 1 и агонист TRPM8.
11. Композиция по п. 10, отличающаяся тем, что агонист TRPM8 включает, по меньшей мере, один из ментола; ментиллактата; N-этил-п-ментан-3-карбоксамида; N-этоксикарбонилметил-п-ментан-3-карбоксамида; N-(4-метоксифенил)-п-ментан-3-карбоксамида; N-трет-бутил-п-ментан-3-карбоксамида; N,2,3-триметил-2-изопропилбутанамида; N-(4-цианометилфенил)-п-ментанкарбоксамида; N-(4-сульфамоилфенил)-п-ментанкарбоксамида; N-(4-цианофенил)-п-ментанкарбоксамида; N-(4-ацетилфенил)-п-ментанкарбоксамида; N-(4-гидроксиметилфенил)-п-ментанкарбоксамида; N-(3-гидрокси-4-метоксифенил)-п-ментанкарбоксамида; изопулегола; и/или (-)-ментоксипропан-1,2-диола.
12. Композиция, содержащая соединение по п. 1 и, по меньшей мере, один из агониста TRPA1 или агониста TRPV1.
13. Композиция по п. 12, отличающаяся тем, что агонист TRPA1 представляет собой, по меньшей мере, один из аллилизотиоцианата; ментола; пероксида; метилсалицилата; коричного альдегида; бензилового спирта; солей цинка; и/или ванилин изобутирата.
14. Композиция по п. 12, отличающаяся тем, что агонист TRPV1 представляет собой, по меньшей мере, один из капсаицина; пиперина; ваниллилбутилового эфира; ваниллилэтилового эфира; ментола; пероксида; солей цинка; или антигистамина.
15. Соединение по п. 1, имеющее структуру:
Figure 00000002
R1 выбран из Н, алкила, аминоалкила, алкокси;
Q=Н2, О, -OR1, -N(R1)2, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
V=NR1, О, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
W=H2, O;
X, Y = независимо выбраны из H, арила, нафтила для n=0;
X, Y = алифатическая СН2 или ароматическая СН для n≥1 и Z выбран из алифатической СН2, ароматической СН или гетероатома;
A = низший алкокси, низший алкилтио, арил, замещенный арил или конденсированный арил; и
стереохимия является переменной в положениях, отмеченных *.
16. Соединение по п. 15, имеющее структуру:
Figure 00000003
17. Соединение по п. 1, имеющее структуру:
Figure 00000004
R1 выбран из Н, алкила, аминоалкила, алкокси;
Q=Н2, О, -OR1, -N(R1)2, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
V=NR1, О, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
W=H2, O;
X, Y = независимо выбраны из H, арила, нафтила для n=0;
X, Y = алифатическая СН2 или ароматическая СН для n≥1 и Z выбран из алифатической СН2, ароматической СН или гетероатома;
A = низший алкокси, низший алкилтио, арил, замещенный арил или конденсированный арил; и
стереохимия является переменной в положениях, отмеченных *.
18. Композиция для личной гигиены, содержащая соединение, имеющее следующую структуру:
Figure 00000005
R1 выбран из Н, алкила, аминоалкила, алкокси;
Q=Н2, О, -OR1, -N(R1)2, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
V=NR1, O, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
W=H2, O;
X, Y = независимо выбраны из H, арила, нафтила для n=0;
X, Y = алифатическая СН2 или ароматическая СН для n≥1 и Z выбран из алифатической СН2, ароматической СН или гетероатома;
A = низший алкокси, низший алкилтио, арил, замещенный арил или конденсированный арил;
стереохимия является переменной в положениях, отмеченных *; и
при этом соединение активирует, по меньшей мере, один из TRPA1, TRPV1 или TRPM8.
19. Композиция для личной гигиены по п. 18, отличающаяся тем, что соединение при концентрации приблизительно 5,2⋅10-5% обеспечивает:
a) большую активацию TRPM8, чем WS5 при концентрации приблизительно 30 мМ;
b) большую активацию TRPA1, чем аллилизотиоцианат при концентрации приблизительно 50 мМ; и
с) большую активацию TRPV1, чем капсаицин при концентрации приблизительно 350 нМ.
20. Композиция для личной гигиены по п. 18, отличающаяся тем, что соединение при концентрации приблизительно 5,2⋅10-5% обеспечивает большую активацию TRPM8, чем WS5 при концентрации приблизительно 30 мМ.
21. Композиция для личной гигиены по п. 18, отличающаяся тем, что соединение имеет структуру:
Figure 00000006
R1 выбран из Н, алкила, аминоалкила, алкокси;
Q=Н2, О, -OR1, -N(R1)2, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
V=NR1, O, -OPO(OR1)x, -PO(OR1)x, -P(OR1)x, где x=1-2;
W=H2, O;
X, Y = независимо выбраны из H, арила, нафтила для n=0;
X, Y = алифатическая СН2 или ароматическая СН для n≥1 и Z выбран из алифатической СН2, ароматической СН или гетероатома;
A = низший алкокси, низший алкилтио, арил, замещенный арил или конденсированный арил; и
стереохимия является переменной в положениях, отмеченных *.
22. Композиция для личной гигиены по п. 21, отличающаяся тем, что соединение имеет структуру:
Figure 00000007
RU2016138746A 2014-04-23 2015-04-23 Циклогексанкарбоксамид с охлаждающими свойствами RU2016138746A (ru)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201461982970P 2014-04-23 2014-04-23
US201461982968P 2014-04-23 2014-04-23
US61/982,968 2014-04-23
US61/982,970 2014-04-23
PCT/US2015/027249 WO2016036423A2 (en) 2014-04-23 2015-04-23 Compositions for deposition on biological surfaces

Publications (2)

Publication Number Publication Date
RU2016138746A3 RU2016138746A3 (ru) 2018-05-24
RU2016138746A true RU2016138746A (ru) 2018-05-24

Family

ID=53055119

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2016138746A RU2016138746A (ru) 2014-04-23 2015-04-23 Циклогексанкарбоксамид с охлаждающими свойствами

Country Status (11)

Country Link
US (5) US9492411B2 (ru)
EP (2) EP3134080A1 (ru)
JP (1) JP2017518963A (ru)
KR (1) KR20160136383A (ru)
CN (2) CN106458861B (ru)
AU (2) AU2015312408B2 (ru)
BR (2) BR112016024691A2 (ru)
CA (2) CA2944160A1 (ru)
MX (2) MX2016013618A (ru)
RU (1) RU2016138746A (ru)
WO (2) WO2016036423A2 (ru)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112016024691A2 (pt) 2014-04-23 2017-08-15 Procter & Gamble ciclo-hexanocarboxamida com propriedades de resfriamento
CN104880428B (zh) * 2015-06-23 2016-07-06 山西振东安特生物制药有限公司 一种胶体果胶铋或含胶体果胶铋制剂中铋含量的测定方法
CA3000021C (en) * 2015-10-22 2020-10-13 The Procter & Gamble Company Method of separating stereoisomers using supercritical fluid chromatography
AU2016342264A1 (en) * 2015-10-22 2018-04-05 The Procter & Gamble Company Synthesis of cyclohexane carboxamide derivatives useful as sensates in consumer products
BR112018012071A2 (pt) * 2015-12-18 2018-11-27 Procter & Gamble síntese de derivados de éster de ciclo-hexano úteis como elementos sensoriais nos produtos destinados ao consumidor
EP3506885A1 (en) * 2016-09-01 2019-07-10 The Procter and Gamble Company Medication with improved taste and sensory experience
EP3876923A1 (en) * 2018-11-07 2021-09-15 The Procter & Gamble Company Cyclohexanecarboxamide derivatives for promoting thermogenesis in adipose tissue
CN113194909A (zh) * 2018-12-20 2021-07-30 宝洁公司 具有改善的稳定性的头皮护理组合物
CN110357833B (zh) * 2019-06-03 2022-05-24 杭州维坦医药科技有限公司 芳杂乙酰胺类衍生物及其制备和应用
WO2021174475A1 (en) * 2020-03-05 2021-09-10 Givaudan Sa Organic compounds
US11998628B2 (en) 2021-11-11 2024-06-04 Colgate-Palmolive Company Personal care compositions
WO2023147852A1 (en) 2022-02-02 2023-08-10 Symrise Ag Compositions (iii)
CN115006374A (zh) * 2022-07-13 2022-09-06 广州文翰生物科技有限公司 香兰基丁醚在制备治疗头屑和体癣产品中的应用

Family Cites Families (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1351762A (en) 1915-03-11 1920-09-07 Bertell W King Means for inscribing unexposed photographic films, plates, or the like
US3111127A (en) 1961-06-27 1963-11-19 Brown & Williamson Tobacco Smoking tobacco product and method of making the same
PH10359A (en) 1971-02-04 1977-01-05 Wilkinson Sword Ltd N-substituted-p-methane-3-carboxamides having physiological cooling activity and compositions containing them
US4150052A (en) 1971-02-04 1979-04-17 Wilkinson Sword Limited N-substituted paramenthane carboxamides
GB1315626A (en) 1971-02-04 1973-05-02 Wilkinson Sword Ltd Substituted p-menthanes and compositions containing them
US4136163A (en) 1971-02-04 1979-01-23 Wilkinson Sword Limited P-menthane carboxamides having a physiological cooling effect
US4193936A (en) 1971-02-04 1980-03-18 Wilkinson Sword Limited N-substituted paramenthane carboxamides
US4178459A (en) 1971-02-04 1979-12-11 Wilkinson Sword Limited N-Substituted paramenthane carboxamides
US4157384A (en) 1972-01-28 1979-06-05 Wilkinson Sword Limited Compositions having a physiological cooling effect
BE795751A (fr) 1972-02-28 1973-08-21 Unilever Nv Compositions aromatisees contenant des composes qui donnent une sensation de froid
GB1421743A (en) 1972-04-18 1976-01-21 Wilkinson Sword Ltd Ingestible topical and other compositions
US4153679A (en) 1972-04-18 1979-05-08 Wilkinson Sword Limited Acyclic carboxamides having a physiological cooling effect
GB1436329A (en) 1972-08-07 1976-05-19 Unilever Ltd Esters of menthol and a heterocyclic carboxylic acid and their use in cosmetic preparations
LU68016A1 (ru) 1973-07-13 1975-04-11
JPS5888334A (ja) 1981-11-20 1983-05-26 Takasago Corp ３−ｌ−メントキシプロパン−１、２−ジオ−ル
EP0310299A1 (en) 1987-09-28 1989-04-05 The Procter & Gamble Company Beta-amino acid ester derivatives of alcoholic actives having extended duration of activity
US5009893A (en) 1989-07-17 1991-04-23 Warner-Lambert Company Breath-freshening edible compositions of methol and a carboxamide
DE8911246U1 (de) 1989-09-21 1991-01-24 Wilkinson Sword GmbH, 5650 Solingen Rasierapparatekopf, insbesondere Rasierklingeneinheit
US5095619A (en) 1990-09-28 1992-03-17 The Gillette Company Shaving system
DK0485170T3 (da) 1990-11-06 1995-12-11 Wrigley W M Jun Co Forbedret smag under anvendelse af menthonkataler
DE4110973A1 (de) 1991-04-05 1992-10-08 Haarmann & Reimer Gmbh Mittel mit physiologischem kuehleffekt und fuer diese mittel geeignete wirksame verbindungen
ATE158163T1 (de) 1992-05-18 1997-10-15 Procter & Gamble Zusammensetzungen mit kühleffekt
DE4226043A1 (de) 1992-08-06 1994-02-10 Haarmann & Reimer Gmbh Mittel mit physiologischem Kühleffekt und für diese Mittel geeignete wirksame Verbindungen
JP2978043B2 (ja) 1993-09-16 1999-11-15 高砂香料工業株式会社 （２ｓ）−３−｛（１ｒ，２ｓ，５ｒ）−［ ５−メチル−２−（１−メチルエチル）シクロヘキシル ］オキシ｝−１，２−プロパンジオール，その製造方法および用途
US5643588A (en) 1994-11-28 1997-07-01 The Procter & Gamble Company Diaper having a lotioned topsheet
US6944952B1 (en) 1994-07-01 2005-09-20 The Gillette Company Shaving system
US6298558B1 (en) 1994-10-31 2001-10-09 The Gillette Company Skin engaging member
US6861571B1 (en) 1994-11-28 2005-03-01 The Procter & Gamble Company Article having a lotioned topsheet
US5713131A (en) 1995-06-30 1998-02-03 The Gillette Company Shaving aid composite with a non-volatile cooling agent
US5653971A (en) 1995-06-30 1997-08-05 The Gillette Company Shaving aid composite with an inclusion complex of a skin-soothing agent and a cyclodextrin
US5843466A (en) 1995-08-29 1998-12-01 V. Mane Fils S.A. Coolant compositions
US5725865A (en) 1995-08-29 1998-03-10 V. Mane Fils S.A. Coolant compositions
US5711076A (en) 1996-03-27 1998-01-27 The Gillette Company Shaving system with improved guard structure
GB9820233D0 (en) 1998-09-18 1998-11-11 Quest Int Improvements in or relating to insect repellents
US6301785B1 (en) 2000-02-18 2001-10-16 The Gillette Company Shaving aid strip for razor cartridge
JP2001294546A (ja) 2000-02-28 2001-10-23 Takasago Internatl Corp （１’Ｒ，２’Ｓ，５’Ｒ）３−ｌ−メントキシアルカン−１−オール冷感剤
ATE380474T1 (de) 2000-05-23 2007-12-15 Nestle Sa Verwendung von alpha-ketoenaminderivaten als kühlende mittel
DE10036184A1 (de) 2000-07-24 2002-02-14 Aventis Cropscience Gmbh Substituierte Sulfonylaminomethylbenzoesäure(derivate) und Verfahren zu ihrer Herstellung
US6365215B1 (en) 2000-11-09 2002-04-02 International Flavors & Fragrances Inc. Oral sensory perception-affecting compositions containing dimethyl sulfoxide, complexes thereof and salts thereof
JP4454838B2 (ja) 2000-12-12 2010-04-21 高砂香料工業株式会社 温感組成物
JP2005530763A (ja) 2002-05-13 2005-10-13 アイシーエージェン，インコーポレイティド カリウム・チャネル調節物質としてのビス−ベンズイミダゾール及び関連化合物
JP2004059474A (ja) * 2002-07-26 2004-02-26 T Hasegawa Co Ltd ｐ−メンタン誘導体およびこれを含有する冷感剤
JP4018032B2 (ja) 2003-06-17 2007-12-05 高砂香料工業株式会社 毛髪及び身体洗浄剤組成物
EP1656144B2 (en) 2003-07-02 2017-12-20 Genentech, Inc. Trp-p8 active compounds and therapeutic treatment methods
WO2005020897A2 (en) 2003-08-22 2005-03-10 Dendreon Corporation Compositions and methods for the treatment of disease associated with trp-p8 expression
EP1685093B3 (en) 2003-11-21 2012-04-11 Givaudan SA N-substituted p-menthane carboxamide and use of n-substituted p-menthane carboxamides
US20080300314A1 (en) 2003-11-21 2008-12-04 Givaudan Sa Cooling Compounds
US7121754B2 (en) 2003-12-08 2006-10-17 Eveready Battery Company, Inc. Shaving apparatus with pivot-actuated valve for delivery of shaving aid material
US20070155755A1 (en) * 2004-02-23 2007-07-05 Wei Edward T N-arylshydroxyalkylidene-carboxamide compositions and methods
US7189760B2 (en) 2004-04-02 2007-03-13 Millennium Specialty Chemicals Physiological cooling compositions containing highly purified ethyl ester of N-[[5-methyl-2-(1-methylethyl) cyclohexyl] carbonyl]glycine
GB0425661D0 (en) 2004-11-23 2004-12-22 Givaudan Sa Organic compounds
BRPI0607407A2 (pt) 2005-03-01 2009-09-01 Givaudan Sa derivados de mentano carboxamida tendo propriedades de refrescáncia
WO2006103401A2 (en) 2005-03-29 2006-10-05 Paget, Hugh, Charles, Edward N-alkylcarbonyl-amino acid ester and n-alkylcarbonyl-amino lactone compounds and their use
US20060225285A1 (en) 2005-04-12 2006-10-12 Unilever Home & Personal Care Usa, Division Of Conopco, Inc. Razor head with mild cleansing composition as a shaving aid
WO2006125334A1 (en) 2005-05-27 2006-11-30 Givaudan Sa Cooling compounds
US8157918B2 (en) 2005-09-30 2012-04-17 Philip Morris Usa Inc. Menthol cigarette
CA2623545C (en) 2005-10-05 2013-04-09 Cadbury Adams Usa Llc Cooling compositions
US7772266B2 (en) 2006-02-15 2010-08-10 Dendreon Corporation Small-molecule modulators of TRP-P8 activity
WO2007095340A2 (en) 2006-02-15 2007-08-23 Dendreon Corporation Small-molecule modulators of trp-p8 activity
JP2009529545A (ja) 2006-03-15 2009-08-20 ジボダン エス エー パラ置換２−アルコキシフェノール化合物
BRPI0721140A2 (pt) 2006-12-20 2014-04-01 Givaudan Nederland Services Bv P-mentano-3-carboxamida n-substituída e usos da mesma.
GB0704163D0 (en) 2007-03-02 2007-04-11 Quest Int Serv Bv Compositions comprising a physiological coolant
US8377422B2 (en) 2007-12-07 2013-02-19 Givaudan S.A. Carboxamide derivatives having cooling properties
WO2009076792A1 (en) 2007-12-19 2009-06-25 Givaudan Sa Cooling compounds
US20100297038A1 (en) 2008-01-17 2010-11-25 Givaudan S.A. Benzimidazole Derivatives And Their Use As Cooling Agents
CN102014863A (zh) 2008-03-07 2011-04-13 永备电池有限公司 剃须辅助材料
DE102008015426A1 (de) 2008-03-20 2009-09-24 Beiersdorf Ag Kühlende kosmetische oder dermatologische Zubereitungen mit einem Gehalt an (1R,2S,5R)-2-Isopropyl-5-methyl-N-(2-(pyridyn-2-yl)ethyl-cyclohexancarboxamid und/oder (1R,2S,5R)-N-(4-(Cyanomethyl)-phenyl)-2-isopropyl-5-methylcyclohexancarboxamid zu Reduktion von Hautrötungen
DE102008015424A1 (de) 2008-03-20 2009-09-24 Beiersdorf Ag Kühlende kosmetische oder dermatologische Zubereitungen mit einem Gehalt an (1R,2S,5R)-2-Isopropyl-5-methyl-N-(2-(pyridyn-2-yl)ethyl-cyclohexancarboxamid und/oder (1R,2S,5R)-N-(4-(Cyanomethyl)-phenyl)-2-isopropyl-5- methylcyclohexancarboxamid mit Menthoxypropandiol
JP5384641B2 (ja) * 2008-08-15 2014-01-08 ザ プロクター アンド ギャンブル カンパニー 消費者製品における感覚剤として有用なシクロヘキサン誘導体の合成
ES2626230T3 (es) 2008-11-20 2017-07-24 The Procter & Gamble Company Composiciones para la higiene personal que proporcionan una sensación refrescante mejorada
FR2944790B1 (fr) 2009-04-23 2012-06-01 Mane Fils V Nouveaux composes a effet physiologique
US8487130B2 (en) 2009-04-27 2013-07-16 International Flavors & Fragrances Inc. Menthylcarboxamides and their use as cooling agents
US8664261B2 (en) 2009-05-05 2014-03-04 Givaudan S.A. Organic compounds having cooling properties
US9446267B2 (en) 2009-10-06 2016-09-20 Symrise Ag Products comprising a flavoring agent composition
GB201103103D0 (en) 2011-02-23 2011-04-06 Givaudan Sa Organic compounds
US9023776B2 (en) 2011-07-26 2015-05-05 Givaudan S.A. Rinse-off compositions comprising lactoyl ethanolamine and a menthanecarboxamide compound
AU2013323689B2 (en) 2012-09-28 2016-09-22 The Gillette Company Llc A skin engaging shaving aid member comprising at least one thermally resilient sensate
US20140090255A1 (en) 2012-09-28 2014-04-03 The Gillette Company Skin Engaging Member Comprising At Least One Thermally Resilient Sensate
BR112016024691A2 (pt) 2014-04-23 2017-08-15 Procter & Gamble ciclo-hexanocarboxamida com propriedades de resfriamento
CN106255495B (zh) 2014-04-29 2019-10-22 宝洁公司 用于制备含铋的液体药物悬浮液的方法
US20160338928A1 (en) 2015-05-22 2016-11-24 The Gillette Company Skin engaging member comprising a cyclohexanecarboxamide derivative

Also Published As

Publication number Publication date
JP2017518963A (ja) 2017-07-13
EP3134081A2 (en) 2017-03-01
MX2016013618A (es) 2017-02-28
EP3134081B1 (en) 2020-04-22
CN106458861A (zh) 2017-02-22
KR20160136383A (ko) 2016-11-29
CA2944160A1 (en) 2015-10-29
WO2016036423A3 (en) 2016-06-09
CN106458861B (zh) 2020-05-19
US9492411B2 (en) 2016-11-15
WO2016036423A2 (en) 2016-03-10
RU2016138746A3 (ru) 2018-05-24
US20170079939A1 (en) 2017-03-23
CA2946383A1 (en) 2016-03-10
EP3134080A1 (en) 2017-03-01
US20150306050A1 (en) 2015-10-29
AU2015312408B2 (en) 2018-02-01
MX2016013617A (es) 2017-02-28
US9974761B2 (en) 2018-05-22
AU2015249706A1 (en) 2016-11-03
BR112016024573A2 (pt) 2017-08-15
US20150307447A1 (en) 2015-10-29
US20180228746A1 (en) 2018-08-16
US20170119639A1 (en) 2017-05-04
CN106232111A (zh) 2016-12-14
AU2015312408A1 (en) 2016-10-27
BR112016024691A2 (pt) 2017-08-15
WO2015164553A1 (en) 2015-10-29

Similar Documents

Publication Publication Date Title
RU2016138746A (ru) Циклогексанкарбоксамид с охлаждающими свойствами
CY1123270T1 (el) Υποκατεστημενες ενωσεις βενζαλδεϋδης και μεθοδοι για τη χρηση τους στην αυξηση της οξυγονωσης των ιστων
EA202092001A1 (ru) Соединения для лечения болезни гентингтона
EA201591774A1 (ru) Замещенные ароматические соединения для лечения легочного фиброза, фиброза печени, фиброза кожи и фиброза сердца
EA201592198A1 (ru) Производные сульфамоилтиофенамида и их применение в качестве медикаментов для лечения гепатита b
EA201690598A1 (ru) Аминогетероарил бензамиды в качестве ингибиторов киназы
EA201691579A1 (ru) Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b
PE20151994A1 (es) Modificador del sabor dulce
CY1123263T1 (el) Πολυκυκλικες ενωσεις ως αναστολεις κινασης τυροσινης bruton
EA201492281A1 (ru) Соединения n-арилтриазола в качестве антагонистов рецепторов лизофосфатидной кислоты (lpar)
UY31050A1 (es) Antagonistas de trpv1 y usos de los mismos
RU2015113638A (ru) Кристаллическое вещество и содержащий его фармацевтический препарат
ECSP14030538A (es) Inhibidores de dgat1 de éter cíclico de cabeza de puente
AR094997A1 (es) Sales y formas sólidas de (s)-3-(4-((4-(morfolinometil)bencil)oxi)-1-oxoisoindolin-2-il)piperidin-2,6-diona y composiciones que las comprenden y sus usos
EA201691881A1 (ru) Новые соединения
EA201891379A1 (ru) Ингибиторы тирозинкиназы брутона и способы их применения
EA201591280A1 (ru) Полимиксины, композиции, способы получения и способы применения
EA201400058A1 (ru) Соединения и композиции на основе амидопиридиловых эфиров и их применение против паразитов
EA201391265A1 (ru) Амиды индолкарбоновых и бензимидазолкарбоновых кислот в качестве инсектицидов и акарицидов
EA201791671A1 (ru) 4-замещенные соединения бензоксаборола и их применение
CY1123880T1 (el) Καινοτομοι 5-ητ2 ανταγωνιστες
NZ751217A (en) Benzo-fused heterocyclic derivatives useful as agonists of gpr120
AR086803A1 (es) Derivados de oxazetidinas, composiciones farmaceuticas y cosmeticas que los contienen y uso de los mismos para tratar enfermedades dermatologicas fundamentalmente, y del aparato respiratorio, digestivo y cardiovascular, entre otras
EA201500737A1 (ru) Пиразолилкарбоксамиды ii в качестве ингибиторов crac каналов
RU2016130613A (ru) Композиция для ухода за полостью рта

Legal Events

Date Code Title Description
FA92 Acknowledgement of application withdrawn (lack of supplementary materials submitted)

Effective date: 20190114

FZ9A Application not withdrawn (correction of the notice of withdrawal)

Effective date: 20190114

FA92 Acknowledgement of application withdrawn (lack of supplementary materials submitted)

Effective date: 20190829