RU2013127611A - Модуляторы глюкагонового рецептора - Google Patents

Модуляторы глюкагонового рецептора Download PDF

Info

Publication number
RU2013127611A
RU2013127611A RU2013127611/04A RU2013127611A RU2013127611A RU 2013127611 A RU2013127611 A RU 2013127611A RU 2013127611/04 A RU2013127611/04 A RU 2013127611/04A RU 2013127611 A RU2013127611 A RU 2013127611A RU 2013127611 A RU2013127611 A RU 2013127611A
Authority
RU
Russia
Prior art keywords
optionally substituted
alkyl
pharmaceutically acceptable
acceptable salt
cycloalkyl
Prior art date
Application number
RU2013127611/04A
Other languages
English (en)
Inventor
Гэри Эрик ЭСПНИС
Мэри Тереза ДИДЮК
Кевин Джеймс Филипски
Эйнджел ГУЗМАН-ПЕРЕЗ
Джеффри Аллен Пфефферкорн
Бенджамин Доусон Стивенс
Мейхуа Майк Ту
Original Assignee
Пфайзер Инк.
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 Пфайзер Инк. filed Critical Пфайзер Инк.
Publication of RU2013127611A publication Critical patent/RU2013127611A/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/08—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Rheumatology (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pyridine Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

1. Соединение Формулы Iили его фармацевтически приемлемая соль, гдеRпредставляет собой фенил-замещенный гало или трифторметилом;или 6-членную гетероарильную группу, которая, необязательно, конденсирована с (С-С)циклоалкилом, фенилом или 5-6 членным гетероарилом, и где необязательно конденсированная 6-членная гетероарильная группа, необязательно, замещена одним - четырьмя заместителями, где каждый независимо выбирают из гало, -S(O)-(С)алкила, гидрокси, -C(O)NRR, циано, (С-С)алкила, необязательно, замещенного одним - тремя фторами, или (С-С)алкокси, необязательно, замещенного одним - тремя фторами;Rи Rкаждый независимо представляет собой Н или (С-С)алкил;Rпредставляет собой Н;Rпредставляет собой -(СН)СОН;А, А, Аи Акаждый независимо представляет собой CRили N, при условии, что один или два из А, А, Аи Апредставляют собой N и при дополнительном условии, что Аи Аоба не являются N;Rв каждом случае, независимо, представляет собой Н, гало, циано, (С-С)алкил, необязательно, замещенный одним - тремя фторами, или (С-С)алкокси, необязательно замещенный одним - тремя фторами;L представляет собой -CH(R)-X-;X представляет собой NH;Rпредставляет собой (С-С)алкил, который необязательно замещен одним - тремя фторами, гидрокси или метокси; (С-С)циклоалкил, который необязательно замещен одним - двумя (С-С)алкилами, которые необязательно замещены одним - тремя фторами или одним - двумя (С-С)алкилами, и где один - два углерода (С-С)циклоалкила могут быть заменены NH, N(С-С)алкилом, О или S; или (С-С)циклоалкил-(С-С)алкил, где (С-С)циклоалкильная группа упомянутого (С-С)циклоалкил-(С-С)алкила необязательно замещена одним - двумя (С-С)алкилами, которые, необязательно, замещены одним - тр�

Claims (10)

1. Соединение Формулы I
Figure 00000001
или его фармацевтически приемлемая соль, где
R1 представляет собой фенил-замещенный гало или трифторметилом;
или 6-членную гетероарильную группу, которая, необязательно, конденсирована с (С4-С7)циклоалкилом, фенилом или 5-6 членным гетероарилом, и где необязательно конденсированная 6-членная гетероарильная группа, необязательно, замещена одним - четырьмя заместителями, где каждый независимо выбирают из гало, -S(O)2-(С1-3)алкила, гидрокси, -C(O)NRaRb, циано, (С1-С6)алкила, необязательно, замещенного одним - тремя фторами, или (С1-С6)алкокси, необязательно, замещенного одним - тремя фторами;
Ra и Rb каждый независимо представляет собой Н или (С1-С3)алкил;
R2 представляет собой Н;
R3 представляет собой -(СН2)2СО2Н;
А1, А2, А3 и А4 каждый независимо представляет собой CR4 или N, при условии, что один или два из А1, А2, А3 и А4 представляют собой N и при дополнительном условии, что А2 и А3 оба не являются N;
R4 в каждом случае, независимо, представляет собой Н, гало, циано, (С1-С3)алкил, необязательно, замещенный одним - тремя фторами, или (С1-С3)алкокси, необязательно замещенный одним - тремя фторами;
L представляет собой -CH(R5)-X-;
X представляет собой NH;
R5 представляет собой (С1-С6)алкил, который необязательно замещен одним - тремя фторами, гидрокси или метокси; (С3-С7)циклоалкил, который необязательно замещен одним - двумя (С1-С3)алкилами, которые необязательно замещены одним - тремя фторами или одним - двумя (С1-С3)алкилами, и где один - два углерода (С3-С7)циклоалкила могут быть заменены NH, N(С1-С3)алкилом, О или S; или (С3-С7)циклоалкил-(С1-С6)алкил, где (С3-С7)циклоалкильная группа упомянутого (С3-С7)циклоалкил-(С1-С6)алкила необязательно замещена одним - двумя (С1-С3)алкилами, которые, необязательно, замещены одним - тремя фторами;
В1, В2, В3 и В4 каждый независимо представляет собой CR6 или N, при условии, что не больше, чем два из В1, В2, В3 и В4 представляют собой N; и
R6 в каждом случае, независимо представляет собой Н, гало, (С1-С3)алкил, необязательно замещенный одним - тремя фторами, или (С1-С3)алкокси, необязательно замещенный одним - тремя фторами.
2. Соединение по п. 1 или его фармацевтически приемлемая соль, где R5 представляет собой этил, пропил, изопропил, т-бутил, пентил, неопентил, циклопропил, циклобутил, циклопентил, циклогексил или циклопропилметил, где каждый необязательно замещен 1-3 фторами и, где каждый упомянутый циклопропил, циклобутил, циклопентил, циклогексил, необязательно замещен 1-2 метилами.
3. Соединение по п. 1 или его фармацевтически приемлемая соль, где R1 представляет собой 4-фторметилфенил или 4-хлорфенил; и R4 и R6 в каждом случае представляет собой Н.
4. Соединение по п. 3 или его фармацевтически приемлемая соль, где В1 представляет собой N и В2, В3 и В4 каждый представляет собой CR6; В2 представляет собой N и В1, В3 и В4 каждый представляет собой CR6; В1 и В4 каждый представляет собой N и В2 и В3 каждый представляет собой CR6; В2 и В3 каждый представляет собой N и В1 и В4 каждый представляет собой CR6; или В1 и В3 каждый представляет собой N и В2 и В4 каждый представляет собой CR6.
5. Соединение по п. 1 или его фармацевтически приемлемая соль, где А1 представляет собой N и А2, А3 и А4 каждый представляет собой CR4; А2 представляет собой N и А1, А3 и А4 каждый представляет собой CR4; А1 и А4 каждый представляет собой N и А2 и А3 каждый представляет собой CR4; или А1 и А3 каждый представляет собой N и А2 и А4 каждый представляет собой CR4.
6. 3-[(6-{(S)-3-метил-1-[2-(4-трифторметилфенил)пиримидин-5-iл]бутиламино}пиридин-3-карбонил)амино]пропановая кислота или его фармацевтически приемлемая соль.
7. Фармацевтическая композиция, содержащая (i) соединение по п. 1 или его фармацевтически приемлемую соль и (ii) фармацевтически приемлемый эксципиент, разбавитель или носитель.
8. Композиция по п. 7, где упомянутое соединение или упомянутая его фармацевтически приемлемая соль, присутствуют в терапевтически эффективном количестве.
9. Применение соединения по п. 1 или его фармацевтически приемлемой соли при изготовлении медикамента для лечения или отсрочки развития или появления диабета Типа 2 и диабетзависимых расстройств.
10. Применение соединения по п. 1 или его фармацевтически приемлемой соли при изготовлении медикамента для лечения заболевания, состояния или расстройства, модулируемого деактивацией рецептора глюкагона.
RU2013127611/04A 2010-12-23 2011-12-09 Модуляторы глюкагонового рецептора RU2013127611A (ru)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201061426600P 2010-12-23 2010-12-23
US61/426,600 2010-12-23
US201161562008P 2011-11-21 2011-11-21
US61/562,008 2011-11-21
PCT/IB2011/055588 WO2012085745A1 (en) 2010-12-23 2011-12-09 Glucagon receptor modulators

Publications (1)

Publication Number Publication Date
RU2013127611A true RU2013127611A (ru) 2015-01-27

Family

ID=45464650

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2013127611/04A RU2013127611A (ru) 2010-12-23 2011-12-09 Модуляторы глюкагонового рецептора

Country Status (17)

Country Link
US (4) US8809342B2 (ru)
EP (1) EP2655331A1 (ru)
JP (1) JP5694561B2 (ru)
KR (1) KR101506829B1 (ru)
CN (1) CN103261165B (ru)
AR (1) AR084579A1 (ru)
AU (1) AU2011346670B2 (ru)
BR (1) BR112013016033A2 (ru)
CA (1) CA2822017C (ru)
MX (1) MX2013006768A (ru)
NZ (1) NZ611529A (ru)
RU (1) RU2013127611A (ru)
SG (1) SG191040A1 (ru)
TW (1) TWI429630B (ru)
UY (1) UY33824A (ru)
WO (1) WO2012085745A1 (ru)
ZA (1) ZA201303950B (ru)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR081331A1 (es) 2010-04-23 2012-08-08 Cytokinetics Inc Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos
AR081626A1 (es) * 2010-04-23 2012-10-10 Cytokinetics Inc Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos
EP2655331A1 (en) * 2010-12-23 2013-10-30 Pfizer Inc Glucagon receptor modulators
CN104350040B (zh) 2012-03-29 2016-06-01 武田药品工业株式会社 芳环化合物
AU2014254262B2 (en) 2013-04-15 2018-08-23 Fmc Corporation Fungicidal carboxamides
HUE039687T2 (hu) * 2013-10-17 2019-01-28 Blueprint Medicines Corp Kompozíciók, amelyek alkalmazhatók KIT-tel kapcsolatos rendellenességek kezelésében való alkalmazásra
CN115052855A (zh) * 2020-03-06 2022-09-13 昊运股份有限公司 酰胺化合物的制备方法、其晶型及其盐类

Family Cites Families (112)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5320825A (en) 1991-05-01 1994-06-14 Trustees Of The University Of Pennsylvania Serotonin reuptake inhibitors for S.P.E.C.T. imaging
WO1994014427A2 (en) 1992-12-23 1994-07-07 Zymogenetics, Inc. Use of skyrin and analogues for the treatment of diabetes mellitus and process for their preparation
EP0617001B1 (en) 1993-03-19 2000-01-26 Merck & Co. Inc. Phenoxyphenylacetic acid derivatives
GB9408185D0 (en) 1994-04-25 1994-06-15 Fujisawa Pharmaceutical Co New benzamide derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same
DE4426346A1 (de) 1994-07-25 1996-02-01 Basf Ag Herbizide Pyrazinderivate
GB2292149A (en) 1994-08-09 1996-02-14 Ferring Res Ltd Peptide inhibitors of pro-interleukin-1beta converting enzyme
WO1996009818A1 (en) 1994-09-27 1996-04-04 Merck & Co., Inc. Endothelin receptor antagonists for the treatment of emesis
US5837719A (en) 1995-08-10 1998-11-17 Merck & Co., Inc. 2,5-substituted aryl pyrroles, compositions containing such compounds and methods of use
JPH11514651A (ja) 1995-10-31 1999-12-14 メルク エンド カンパニー インコーポレーテッド 置換ピリジルピロール、前記化合物を含む組成物及び使用方法
AR008789A1 (es) 1996-07-31 2000-02-23 Bayer Corp Piridinas y bifenilos substituidos
US5776954A (en) 1996-10-30 1998-07-07 Merck & Co., Inc. Substituted pyridyl pyrroles, compositions containing such compounds and methods of use
CA2271893A1 (en) 1996-11-20 1998-05-28 Linda L. Chang Triaryl substituted imidazoles as glucagon antagonists
US5880139A (en) 1996-11-20 1999-03-09 Merck & Co., Inc. Triaryl substituted imidazoles as glucagon antagonists
EP0948496A2 (en) 1996-12-05 1999-10-13 Amgen inc. Substituted pyrimidinone and pyridone compounds and methods of use
WO1998024782A2 (en) 1996-12-05 1998-06-11 Amgen Inc. Substituted pyrimidine compounds and their use
CN1245486A (zh) 1996-12-11 2000-02-23 Basf公司 用作钙蛋白酶抑制剂的酮苯甲酰胺
JPH10259176A (ja) 1997-03-17 1998-09-29 Japan Tobacco Inc 血管新生阻害作用を有する新規アミド誘導体及びその用途
BR9810378A (pt) 1997-07-01 2000-08-29 Novo Nordisk As Composto,uso do mesmo, composição farmacêutica, e, processos de tratar a diabete do tipo i ou do tipo ii, de tratar a hiperglicemia, e de diminuir a glicose do sangue em um mamìfero
US6022884A (en) 1997-11-07 2000-02-08 Amgen Inc. Substituted pyridine compounds and methods of use
KR20010033241A (ko) 1997-12-19 2001-04-25 스티븐 엠. 오드레 치환된 피리딘 및 피리다진 화합물과 그것의 제약학적 용도
PT1177176E (pt) 1999-04-28 2006-08-31 Aventis Pharma Gmbh Derivados de acidos triarilicos como ligandos de receptores ppar.
DK1177187T3 (da) 1999-04-28 2007-10-15 Sanofi Aventis Deutschland Diarylsyrederivater som PPAR-receptorligander
PL352367A1 (en) 1999-05-17 2003-08-25 Novo Nordisk As Glucagon antagonists/inverse agonists
HUP0301501A2 (hu) 2000-06-23 2003-08-28 Novo Nordisk A/S Glükagon antaagonista/inverz agonista vegyületek, ezeket tartalmazó gyógyászati készítmények, valamint a vegyületek alkalmazása gyógyászati készítmények előállítására
AU2002223502A1 (en) 2000-11-17 2002-05-27 Novo-Nordisk A/S Glucagon antagonist/inverse agonist
US20030203946A1 (en) 2000-11-17 2003-10-30 Carsten Behrens Glucagon antagonists/inverse agonists
HUP0303376A3 (en) 2001-02-28 2007-08-28 Merck & Co Inc Acylated piperidine derivatives as melanocortin-4 receptor agonists, and pharmaceutical compositions containing them and use thereof
DE10110749A1 (de) 2001-03-07 2002-09-12 Bayer Ag Substituierte Aminodicarbonsäurederivate
WO2003047626A1 (en) 2001-12-03 2003-06-12 Novo Nordisk A/S Use of a glucokinase activator in combination with a glucagon antagonist for treating type 2 diabetes
JP2005511683A (ja) 2001-12-03 2005-04-28 ノボ　ノルディスク　アクティーゼルスカブ 新規なグルカゴンアンタゴニスト
WO2003051357A1 (en) 2001-12-19 2003-06-26 Novo Nordisk A/S Glucagon receptor antagonists/inverse agonists
AU2002347022A1 (en) 2001-12-20 2003-07-09 Novo Nordisk A/S Benzimidazols and indols as glucagon receptor antagonists/inverse agonisten
PL370989A1 (en) 2001-12-21 2005-06-13 Novo Nordisk A/S Amide derivatives as gk activators
MXPA04007474A (es) 2002-02-01 2004-11-10 Dainippon Pharmaceutical Co Hidrazidas del acido 2-furancarboxilico y composiciones farmaceuticas que la contienen.
EP1487843A4 (en) 2002-03-20 2010-03-10 Metabolex Inc SUBSTITUTED PHENYLACETIC ACIDS
WO2003087044A2 (en) 2002-04-09 2003-10-23 7Tm Pharma A/S Novel carboxamide compounds for use in mch receptor related disorders
AU2003233780A1 (en) 2002-06-27 2004-01-19 Novo Nordisk A/S Novel glucagon antagonists/inverse agonists
PL215132B1 (pl) 2002-06-27 2013-10-31 Novo Nordisk As Pochodna arylokarbonylowa jako srodek terapeutyczny, jej zastosowanie i kompozycja farmaceutyczna ja zawierajaca
WO2004024066A2 (en) 2002-09-12 2004-03-25 Merck & Co., Inc. Method of treating diabetes and related conditions
US7196106B2 (en) 2002-11-05 2007-03-27 Merck & Co., Inc Cyanothiophene derivatives, compositions containing such compounds and methods of use
US20040097557A1 (en) 2002-11-13 2004-05-20 Duffy Joseph L. Cyanothiophene derivatives, compositions containing such compounds and methods of use
CA2508581A1 (en) 2002-12-04 2004-06-17 Merck & Co., Inc. Spirocyclic ureas, compositions containing such compounds and methods of use
AU2003291959A1 (en) 2002-12-20 2004-07-14 Novo Nordisk A/S Novel glucagon antagonists
US20040209928A1 (en) 2002-12-30 2004-10-21 Ravi Kurukulasuriya Glucagon receptor antagonists/inverse agonists
US7151114B2 (en) 2003-01-09 2006-12-19 Boehringer Ingelheim International Gmbh Use of substituted 2-phenylbenzimidazoles as medicaments
DE10300398A1 (de) 2003-01-09 2004-07-22 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verwendung von substituierten 2-Phenylbenzimidazolen als Arzneimittel
WO2004063147A1 (en) 2003-01-10 2004-07-29 Novo Nordisk A/S Salts and solvates of glucagon antagonists
DE602004030318D1 (de) 2003-01-27 2011-01-13 Merck Sharp & Dohme Substituierte pyrazole, zusammensetzungen,die solche verbindungen enthalten, und anwendungsverfahren
MXPA05010937A (es) 2003-04-14 2005-11-25 Inst For Pharm Discovery Inc Derivados de fenilalanina n-(1,3-tiazol-2-il)amino)carbonil)fenil)sulfonil) y compuestos relacionados para el tratamiento de diabetes.
US7138529B2 (en) 2003-04-16 2006-11-21 Hoffmann-La Roche Inc. Substituted 3-cyanothiophene acetamides as glucagon receptor antagonists
JP2006525365A (ja) 2003-04-30 2006-11-09 ジ インスチチュート フォー ファーマシューティカル ディスカバリー、エルエルシー フェニル置換カルボン酸
WO2004100875A2 (en) 2003-05-09 2004-11-25 Merck & Co., Inc. Benzimidazoles, compositions containing such compounds and methods of use
US7355049B2 (en) 2003-06-24 2008-04-08 Hoffmann-La Roche Inc. Biaryloxymethylarenecarboxylic acids as glycogen synthase activator
JP4412098B2 (ja) 2003-07-31 2010-02-10 Ｊｆｅスチール株式会社 溶接熱影響部靭性に優れた低降伏比高強度鋼板及びその製造方法
WO2005014534A1 (en) 2003-08-08 2005-02-17 Transtech Pharma, Inc. Aryl and heteroaryl compounds, compositions, and methods of use
JP2007514794A (ja) 2003-12-19 2007-06-07 メルク　エンド　カムパニー　インコーポレーテッド 環式グアニジン、そのような化合物を含む組成、及び使用方法
WO2005058845A2 (en) 2003-12-19 2005-06-30 Novo Nordisk A/S Novel glucagon antagonists/inverse agonists
EA010888B1 (ru) 2004-05-25 2008-12-30 Пфайзер Продактс, Инк. Тетраазабензо[е]азуленовые производные и их аналоги
ES2428538T3 (es) 2004-05-28 2013-11-08 Eli Lilly And Company Antagonistas del receptor de glucagón, preparación y usos terapéuticos
ES2306165T3 (es) 2004-06-04 2008-11-01 MERCK & CO., INC. Derivados de pirazol, composiciones que contienen dichos compuestos y procedimientos de uso.
CA2569459C (en) * 2004-06-14 2013-01-29 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
AU2005272043B2 (en) 2004-07-07 2010-07-29 Merck Sharp & Dohme Corp. Pyrazole amide derivatives, compositions containing such compounds and methods of use
EP1773330B1 (en) 2004-07-22 2010-05-26 Merck Sharp & Dohme Corp. Substituted pyrazoles, compositions containing such compounds and methods of use
DE102004051188A1 (de) 2004-10-21 2006-04-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Cyanothiophene, deren Herstellung und deren Verwendung als Arzneimittel
US7524870B2 (en) 2004-12-03 2009-04-28 Hoffmann-La Roche Inc. Biaryloxymethylarenecarboxylic acids as glycogen synthase activators
US20060122236A1 (en) * 2004-12-06 2006-06-08 Wood Michael R Substituted biaryl-carboxylate derivatives
PA8660701A1 (es) 2005-02-04 2006-09-22 Pfizer Prod Inc Agonistas de pyy y sus usos
ES2332470T3 (es) 2005-02-11 2010-02-05 Eli Lilly And Company Derivados de tiofeno sustituidos como antagonistas del receptor de glucagon, preparacion y usos terapeuticos.
CN101146762A (zh) 2005-03-21 2008-03-19 默克公司 取代的芳基和杂芳基衍生物
CA2600833A1 (en) 2005-03-30 2006-10-05 Merck & Co., Inc. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
US7709658B2 (en) 2005-07-26 2010-05-04 Merck Sharp & Dohme Corp. Process for synthesizing a substituted pyrazole
US7754717B2 (en) 2005-08-15 2010-07-13 Amgen Inc. Bis-aryl amide compounds and methods of use
RU2440123C2 (ru) 2005-10-06 2012-01-20 Проби Аб Применение lactobacillus для лечения вирусных инфекций
TW200745031A (en) 2005-10-13 2007-12-16 Merck & Co Inc Acyl indoles, compositions containing such compounds and methods of use
AR056574A1 (es) 2005-10-19 2007-10-10 Merck & Co Inc Derivados de pirazol, composiciones que contienen dichos compuestos y procedimientos de uso
JP5199108B2 (ja) 2005-11-14 2013-05-15 ユニヴァーシティー オブ サザン カリフォルニア インテグリン結合小分子
AU2006340002B2 (en) 2005-11-17 2011-12-22 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
ES2393757T3 (es) 2005-11-17 2012-12-27 Eli Lilly & Company Antagonistas de receptor de glucagón, preparación y usos terapéuticos
AU2006341392B2 (en) 2005-11-18 2012-05-17 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
US8691856B2 (en) * 2005-11-22 2014-04-08 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
SI1957484T1 (sl) 2005-11-23 2010-07-30 Lilly Co Eli Antagonisti glukagonskega receptorja, priprava in terapevtske uporabe
WO2007072179A2 (en) 2005-12-19 2007-06-28 Methylgene, Inc. Histone deacetylase inhibitors for enhancing activity of antifungal agents
TW200806611A (en) 2006-02-09 2008-02-01 Daiichi Seiyaku Co Novel amidopropionic acid derivatives and medicine containing the same
AU2007229850A1 (en) 2006-03-23 2007-10-04 Merck & Co., Inc. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
WO2007136577A2 (en) 2006-05-16 2007-11-29 Merck & Co., Inc. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
TW200821284A (en) 2006-10-03 2008-05-16 Merck & Co Inc Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
CN107669669A (zh) 2007-02-09 2018-02-09 症变治疗公司 新颖的胰高血糖素受体拮抗剂
JP2009040702A (ja) 2007-08-07 2009-02-26 Daiichi Sankyo Co Ltd 新規アミドプロピオン酸誘導体を含有する医薬組成物
WO2009035558A1 (en) 2007-09-12 2009-03-19 Merck & Co., Inc. Process for the production of a crystalline glucagon receptor antagonist compound
WO2009057784A1 (ja) * 2007-11-01 2009-05-07 Takeda Pharmaceutical Company Limited 複素環化合物
KR101277560B1 (ko) 2007-12-11 2013-06-25 카딜라 핼쓰캐어 리미티드 글루카곤 안타고니스트 활성 및 ｇｌｐ-1 아고니스트 활성의 펩티드 유사체
US8436043B2 (en) 2008-03-05 2013-05-07 Takeda Pharmaceutical Company Limited Heterocyclic compound
JP5382952B2 (ja) 2008-03-07 2014-01-08 トランス テック ファーマ，インコーポレイテッド 糖尿病の治療のためのオキサジアゾアントラセン化合物
CA2724294A1 (en) 2008-05-16 2009-11-19 Schering Corporation Glucagon receptor antagonists, compositions, and methods for their use
WO2010019828A1 (en) * 2008-08-13 2010-02-18 Metabasis Therapeutics, Inc. Glucagon receptor antagonists
MX2011001708A (es) 2008-08-13 2011-04-26 Metabasis Therapeutics Inc Antagonistas de glucagon.
EP2346830B1 (en) 2008-09-15 2015-05-13 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
CA2738663A1 (en) 2008-10-03 2010-04-08 Schering Corporation Spiro-imidazolone derivatives as glucagon receptor antagonists
WO2010071750A1 (en) 2008-12-19 2010-06-24 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds
WO2010080971A1 (en) 2009-01-12 2010-07-15 Merck Sharp & Dohme Corp. Crystalline polymorphic forms of an antidiabetic compound
US20110281795A1 (en) 2009-01-28 2011-11-17 Songnian Lin Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
WO2010098948A1 (en) 2009-02-13 2010-09-02 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds, compositions containin such compounds and methods of use
US8318667B2 (en) 2009-02-25 2012-11-27 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
TWI491393B (zh) 2009-05-14 2015-07-11 Sumitomo Dainippon Pharma Co Ltd 3- (4-aminophenyl) -2-furancarboxylic acid derivatives and pharmaceutically acceptable salts thereof
WO2010144664A1 (en) 2009-06-12 2010-12-16 Schering Corporation Thiophenes as glucagon receptor antagonists, compositions, and methods for their use
JP2012188352A (ja) 2009-07-13 2012-10-04 Dainippon Sumitomo Pharma Co Ltd ３−（４−置換アルキル−フェニル）−２−フランカルボン酸誘導体およびその薬学的に許容される塩
WO2011027849A1 (ja) 2009-09-04 2011-03-10 武田薬品工業株式会社 複素環化合物
WO2011037815A1 (en) 2009-09-22 2011-03-31 Schering Corporation Novel pyrrolidines as glucagon receptor antagonists, compositions, and methods for their use
CA2794003A1 (en) 2010-03-25 2011-09-29 Merck Sharp & Dohme Corp. Novel spiro imidazolones as glucagon receptor antagonists, compositions, and methods for their use
CA2793949A1 (en) 2010-03-26 2011-09-29 Merck Sharp & Dohme Corp. Novel spiro imidazolone derivatives as glucagon receptor antagonists, compositions, and methods for their use
CN102206172B (zh) 2010-03-30 2015-02-25 中国医学科学院医药生物技术研究所 一组取代双芳基化合物及其制备方法和抗病毒应用
EP2655331A1 (en) * 2010-12-23 2013-10-30 Pfizer Inc Glucagon receptor modulators

Also Published As

Publication number Publication date
WO2012085745A1 (en) 2012-06-28
US8809342B2 (en) 2014-08-19
US20150266861A1 (en) 2015-09-24
EP2655331A1 (en) 2013-10-30
SG191040A1 (en) 2013-08-30
US8933104B2 (en) 2015-01-13
CN103261165B (zh) 2015-08-26
BR112013016033A2 (pt) 2018-06-05
UY33824A (es) 2012-07-31
CA2822017C (en) 2015-04-07
JP2014500306A (ja) 2014-01-09
AR084579A1 (es) 2013-05-29
MX2013006768A (es) 2013-07-22
AU2011346670A1 (en) 2013-07-25
AU2011346670B2 (en) 2015-05-07
TW201302706A (zh) 2013-01-16
TWI429630B (zh) 2014-03-11
CN103261165A (zh) 2013-08-21
KR20130087588A (ko) 2013-08-06
US20140329862A1 (en) 2014-11-06
CA2822017A1 (en) 2012-06-28
JP5694561B2 (ja) 2015-04-01
US20150094338A1 (en) 2015-04-02
US9056834B2 (en) 2015-06-16
NZ611529A (en) 2015-06-26
KR101506829B1 (ko) 2015-03-30
US20120165343A1 (en) 2012-06-28
ZA201303950B (en) 2014-07-30

Similar Documents

Publication Publication Date Title
RU2013127611A (ru) Модуляторы глюкагонового рецептора
RU2460730C2 (ru) Новые производные n-(8-гетероарилтетрагидронафталин-2-ил)-или n-(5-гетероарилхроман-3-ил)-карбоксамида для лечения боли
RU2014121090A (ru) Модуляторы рецептора нмда и их применение
RU2477723C2 (ru) Ингибиторы протеинкиназ (варианты), их применение для лечения онкологических заболеваний и фармацевтическая композиция на их основе
RU2014103587A (ru) Производные циклических аминов в качестве антагонистов рецептора ер4
RU2013137452A (ru) Композиции, содержащие расщепляемое ферментами пролекарство оксикодона
RU2015107803A (ru) Производные дигидроксипиримидинкарбоновой кислоты и их применение в лечении, облегчении или предотвращении вирусного заболевания
RU2016105581A (ru) Способ лечения острого, хронического и подострого кашля и непреодолимого желания откашляться
EA201500266A1 (ru) Ингибиторы репликации вирусов гриппа
JP2011509309A5 (ru)
RU2011105768A (ru) Производные пиперидина в качестве ингибиторов jakз
AR089134A1 (es) Arilos y heteroarilos biciclicos inhibidores de los canales de sodio
RU2013148146A (ru) Производные адамантила
JP2015524472A5 (ru)
RU2015120478A (ru) Пери-карбинолы
RU2012158142A (ru) Противоопухолевое средство, задействующее соединения с ингибирующим эффектом к киназам в комбинации
RU2013140169A (ru) Противоопухолевое терапевтическое средство
JP2017508795A5 (ru)
JP2016531126A5 (ru)
RU2017110211A (ru) ИНГИБИТОРЫ α-АМИНО-β-КАРБОКСИМУКОНАТ-ε-СЕМИАЛЬДЕГИД-ДЕКАРБОКСИЛАЗЫ
RU2013116801A (ru) Ингибиторы notum пектинацетилэстеразы и способы их применения
JP2017508794A5 (ru)
RU2016101958A (ru) Пиразольные соединения в качестве модуляторов fshr и их применение
JP2013533253A5 (ru)
EA201270266A1 (ru) Гетероциклические соединения

Legal Events

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

Effective date: 20160120