RU2011108713A - Антагонисты рецептора сфингозин-1-фосфата (s1p) и способы их применения - Google Patents

Антагонисты рецептора сфингозин-1-фосфата (s1p) и способы их применения Download PDF

Info

Publication number
RU2011108713A
RU2011108713A RU2011108713/04A RU2011108713A RU2011108713A RU 2011108713 A RU2011108713 A RU 2011108713A RU 2011108713/04 A RU2011108713/04 A RU 2011108713/04A RU 2011108713 A RU2011108713 A RU 2011108713A RU 2011108713 A RU2011108713 A RU 2011108713A
Authority
RU
Russia
Prior art keywords
compound according
alkoxy
alkylamino
heteroaryl
cycloalkyl
Prior art date
Application number
RU2011108713/04A
Other languages
English (en)
Other versions
RU2505527C2 (ru
Inventor
Фонг Х. НГУЕН (US)
Фонг Х. НГУЕН
Тод М. ХЕЙДЕЛЬБАУ (US)
Тод М. ХЕЙДЕЛЬБАУ
Кен ЧОУ (US)
Кен ЧОУ
Original Assignee
Аллерган, Инк. (Us)
Аллерган, 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 Аллерган, Инк. (Us), Аллерган, Инк. filed Critical Аллерган, Инк. (Us)
Publication of RU2011108713A publication Critical patent/RU2011108713A/ru
Application granted granted Critical
Publication of RU2505527C2 publication Critical patent/RU2505527C2/ru

Links

Classifications

    • 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
    • C07C233/66—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 halogen atoms or by nitro or nitroso groups
    • 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
    • C07C233/77—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 amino groups
    • C07C233/78—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 amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • 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
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • 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
    • A61P11/06—Antiasthmatics
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/04—Antipruritics
    • 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
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/50—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring 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
    • 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
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or 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
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pulmonology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Furan Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

1. Соединение, имеющее структуру: ! ! где каждый R1 независимо представляет собой -Н или низший алкил; ! каждый из R2 и R3 независимо представляет собой -Н, линейный или разветвленный алкил, циклоалкил, гетероциклическую группу, арил, гетероарил, алкенил, алкинил, галогенид, гидрокси, алкокси, алкиламино, алкилкарбоксил, трифторметил, -N(R4)2, -CN, -CO2R4, -CH2OH, -OCF3, -OCHF2 или -NO2; где каждый R2 находится в мета- или пара-положении относительно карбонильной группировки; ! каждый R4 независимо представляет собой Н, линейный или разветвленный алкил, циклоалкил, арил, гетероарил, галогеноалкил, гидрокси, алкокси, гидроксиалкил, алкилкарбонил, формил, оксикарбонил, карбоксил, алкилкарбоксилат, алкиламид, амино, алкиламино или аминокарбонил; ! каждый из Z1, Z2, Z3, Z4, Z5 и Z6 независимо представляет собой С, N, О или S; ! Х представляет собой Н, F, Cl, Br или I; ! каждое n независимо равно 1-5; и ! р равно 0 или 1; ! при условии, что если каждый из Z1, Z2, Z3, Z4, Z5 и Z6 представляет собой С, р равно 1 и каждый R2 представляет собой -Н, то R3 не является Cl; ! или его фармацевтически приемлемые соли. ! 2. Соединение по п.1, где Х представляет собой F, Cl или Br. ! 3. Соединение по п.2, где каждый R2 независимо представляет собой алкил, галогенид, алкокси или -NO2. ! 4. Соединение по п.1, где р равно 1 и каждый из Z1, Z2, Z3, Z4, Z5, и Z6 представляет собой С. ! 5. Соединение по п.4, имеющее любую из структур: ! ! ! ! ! 6. Соединение по п.1, где р равно 0, Z1 представляет собой О и каждый из Z3, Z4, Z5 и Z6 представляет собой С. ! 7. Соединение по п.6, имеющее любую из приведенных ниже структур: ! ! ! ! ! ! !! 8. Соединение по п.1, где р равно 1 и по меньшей мере один из Z1, Z2, Z3, Z4, Z5 и Z6 представляет собой N. ! 9. Соединение по п

Claims (17)

1. Соединение, имеющее структуру:
Figure 00000001
где каждый R1 независимо представляет собой -Н или низший алкил;
каждый из R2 и R3 независимо представляет собой -Н, линейный или разветвленный алкил, циклоалкил, гетероциклическую группу, арил, гетероарил, алкенил, алкинил, галогенид, гидрокси, алкокси, алкиламино, алкилкарбоксил, трифторметил, -N(R4)2, -CN, -CO2R4, -CH2OH, -OCF3, -OCHF2 или -NO2; где каждый R2 находится в мета- или пара-положении относительно карбонильной группировки;
каждый R4 независимо представляет собой Н, линейный или разветвленный алкил, циклоалкил, арил, гетероарил, галогеноалкил, гидрокси, алкокси, гидроксиалкил, алкилкарбонил, формил, оксикарбонил, карбоксил, алкилкарбоксилат, алкиламид, амино, алкиламино или аминокарбонил;
каждый из Z1, Z2, Z3, Z4, Z5 и Z6 независимо представляет собой С, N, О или S;
Х представляет собой Н, F, Cl, Br или I;
каждое n независимо равно 1-5; и
р равно 0 или 1;
при условии, что если каждый из Z1, Z2, Z3, Z4, Z5 и Z6 представляет собой С, р равно 1 и каждый R2 представляет собой -Н, то R3 не является Cl;
или его фармацевтически приемлемые соли.
2. Соединение по п.1, где Х представляет собой F, Cl или Br.
3. Соединение по п.2, где каждый R2 независимо представляет собой алкил, галогенид, алкокси или -NO2.
4. Соединение по п.1, где р равно 1 и каждый из Z1, Z2, Z3, Z4, Z5, и Z6 представляет собой С.
5. Соединение по п.4, имеющее любую из структур:
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
6. Соединение по п.1, где р равно 0, Z1 представляет собой О и каждый из Z3, Z4, Z5 и Z6 представляет собой С.
7. Соединение по п.6, имеющее любую из приведенных ниже структур:
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
8. Соединение по п.1, где р равно 1 и по меньшей мере один из Z1, Z2, Z3, Z4, Z5 и Z6 представляет собой N.
9. Соединение по п.8, имеющее структуру:
Figure 00000016
или
Figure 00000017
.
10. Соединение по п.1, имеющее структуру:
Figure 00000018
где Х представляет собой Cl, F или Br;
R2 и каждый R3 независимо представляют собой -Н, линейный или разветвленный алкил, циклоалкил, гетероциклическую группу, арил, гетероарил, алкенил, алкинил, галогенид, гидрокси, алкокси, алкиламино, алкилкарбоксил, трифторметил,
-N(R4)2, -CN, -CO2R4, -CH2OH, -OCF3, -OCHF2 или -NO2;
каждый R4 независимо представляет собой Н, линейный или разветвленный алкил, циклоалкил, арил, гетероарил, галогеноалкил, гидрокси, алкокси, гидроксиалкил, алкилкарбонил, формил, оксикарбонил, карбоксил, алкилкарбоксилат, алкиламид, амино, алкиламино или аминокарбонил; и
n равно 1-5.
11. Соединение по п.1, имеющее структуру:
Figure 00000019
где X представляет собой Cl, F или Br;
R2 и каждый R3 независимо представляют собой -Н, линейный или разветвленный алкил, циклоалкил, гетероциклическую группу, арил, гетероарил, алкенил, алкинил, галогенид, гидрокси, алкокси, алкиламино, алкилкарбоксил, трифторметил, -N(R4)2, -CN, -CO2R4, -CH2OH, -OCF3, -OCHF2 или -NO2;
каждый R4 независимо представляет собой Н, линейный или разветвленный алкил, циклоалкил, арил, гетероарил, галогеноалкил, гидрокси, алкокси, гидроксиалкил, алкилкарбонил, формил, оксикарбонил, карбоксил, алкилкарбоксилат, алкиламид, амино, алкиламино или аминокарбонил; и
n равно 1-5.
12. Фармацевтическая композиция, содержащая по меньшей мере одно соединение по п.1 в фармацевтически приемлемом носителе для него.
13. Способ лечения расстройства, связанного с модулированием рецепторов сфингозин-1-фосфата, включающий введение субъекту, нуждающемуся в этом, фармацевтической композиции, содержащей терапевтически эффективное количество по меньшей мере одного соединения по п.1.
14. Способ по п.13, где расстройство представляет собой боль, глаукому, сухость глаз, нарушения ангиогенеза, сердечно-сосудистые расстройства или заживление раны.
15. Способ по п.13, где расстройство представляет собой хроническую боль.
16. Способ по п.13, где расстройство представляет собой острую боль.
17. Способ по п.13, где фармацевтическую композицию вводят перорально.
RU2011108713/04A 2008-08-12 2009-08-12 Антагонисты рецептора сфингозин-1-фосфата (s1p) и способы их применения RU2505527C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US8821708P 2008-08-12 2008-08-12
US61/088,217 2008-08-12
PCT/US2009/053524 WO2010019646A1 (en) 2008-08-12 2009-08-12 Sphingosine-1-phosphate (s1p) receptor antagonists and methods for use thereof

Publications (2)

Publication Number Publication Date
RU2011108713A true RU2011108713A (ru) 2012-09-20
RU2505527C2 RU2505527C2 (ru) 2014-01-27

Family

ID=41165710

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2011108713/04A RU2505527C2 (ru) 2008-08-12 2009-08-12 Антагонисты рецептора сфингозин-1-фосфата (s1p) и способы их применения

Country Status (10)

Country Link
US (1) US8049037B2 (ru)
EP (1) EP2328863A1 (ru)
JP (1) JP5546540B2 (ru)
KR (1) KR20110044893A (ru)
CN (1) CN102119140B (ru)
AU (1) AU2009282017B2 (ru)
BR (1) BRPI0918399A2 (ru)
CA (1) CA2733970A1 (ru)
RU (1) RU2505527C2 (ru)
WO (1) WO2010019646A1 (ru)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2011003990A (es) 2008-10-17 2011-07-28 Exelixis Inc Efectos sinergicos entre antagonistas del receptor esfingosina-1-fosfato y agentes antimicrotubulos.
US8168795B2 (en) * 2009-08-11 2012-05-01 Allergan, Inc. Selective sphingosine-1-phosphate receptor antagonists
WO2011028927A1 (en) * 2009-09-04 2011-03-10 Allergan, Inc. Selective sphingosine-1-phosphate receptor antagonists
EP2598126A2 (en) * 2010-07-30 2013-06-05 Saint Louis University Methods of treating pain
KR101625872B1 (ko) 2015-01-27 2016-06-01 국민대학교산학협력단 스마트단말기의 이벤트 기반의 차량조명 제어시스템 및 그 제어방법, 그리고 이를 위한 컴퓨터로 판독가능한 기록매체

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE756062A (fr) * 1969-09-11 1971-03-11 Boehringer Sohn Ingelheim Derives de 1,1,1-trichlorethane leurs procedes de fabrication et leur utilisation en tant que substances biocides
JPS55111451A (en) * 1979-02-19 1980-08-28 Nippon Kayaku Co Ltd Novel 2-hydroxybenzamide derivative and agricultural and horticultural soil bactericide
EP0146810A3 (de) 1983-12-05 1987-05-13 Solco Basel AG Verfahren zur Herstellung von Sphingosinderivaten
US4659722A (en) * 1984-08-20 1987-04-21 Nippon Kayaku Kabushiki Kaisha Bactericidal N-(2,2,2 trichloroethyl)pyridinecarboxamides
JPS61172860A (ja) * 1985-01-28 1986-08-04 Nippon Kayaku Co Ltd 新規ピリジン誘導体及びそれを有効成分とする農園芸用細菌病防除剤
US5110987A (en) 1988-06-17 1992-05-05 Emory University Method of preparing sphingosine derivatives
ZA902794B (en) 1989-04-18 1991-04-24 Duphar Int Res New 3-n substituted carbamoyl-indole derivatives
US5294722A (en) 1992-04-16 1994-03-15 E. R. Squibb & Sons, Inc. Process for the preparation of imidazoles useful in angiotensin II antagonism
US5403851A (en) 1994-04-05 1995-04-04 Interneuron Pharmaceuticals, Inc. Substituted tryptamines, phenalkylamines and related compounds
AU6310198A (en) 1997-03-12 1998-09-29 Takara Shuzo Co., Ltd. Sphingosine analogues
JP4091250B2 (ja) 1997-09-11 2008-05-28 タカラバイオ株式会社 スフィンゴシン類誘導体及び医薬組成物
WO2000007017A2 (en) * 1998-07-27 2000-02-10 President And Fellows Of Harvard College Method of high-throughput screening
US6946474B2 (en) * 2000-09-14 2005-09-20 Merck & Co., Inc. Nitrogen-containing compounds and their use as glycine transport inhibitors
CA2437358A1 (en) * 2001-01-30 2002-08-22 University Of Virginia Patent Foundation Agonists and antagonists of sphingosine-1-phosphate receptors
AU2002310099A1 (en) * 2001-05-22 2002-12-03 President And Fellows Of Harvard College Identification of anti-protozoal agents
JP4399253B2 (ja) 2001-06-20 2010-01-13 ワイス プラスミノゲンアクチベーターインヒビター−１（ｐａｉ−１）のインヒビターとしての、置換されたインドール酸誘導体
GB0324210D0 (en) * 2003-10-15 2003-11-19 Novartis Ag Organic compounds
GB0405289D0 (en) * 2004-03-09 2004-04-21 Novartis Ag Organic compounds

Also Published As

Publication number Publication date
AU2009282017B2 (en) 2014-08-07
CN102119140B (zh) 2014-09-03
BRPI0918399A2 (pt) 2015-12-29
EP2328863A1 (en) 2011-06-08
CN102119140A (zh) 2011-07-06
AU2009282017A1 (en) 2010-02-18
CA2733970A1 (en) 2010-02-18
WO2010019646A1 (en) 2010-02-18
RU2505527C2 (ru) 2014-01-27
JP5546540B2 (ja) 2014-07-09
JP2012500205A (ja) 2012-01-05
US20100041715A1 (en) 2010-02-18
US8049037B2 (en) 2011-11-01
KR20110044893A (ko) 2011-05-02

Similar Documents

Publication Publication Date Title
RU2011108713A (ru) Антагонисты рецептора сфингозин-1-фосфата (s1p) и способы их применения
RU2016105581A (ru) Способ лечения острого, хронического и подострого кашля и непреодолимого желания откашляться
JP2019509276A5 (ru)
RU2477723C2 (ru) Ингибиторы протеинкиназ (варианты), их применение для лечения онкологических заболеваний и фармацевтическая композиция на их основе
HRP20181048T1 (hr) Neuroaktivni 19-alkoksi-17-supstituirani steroidi, korisni u postupcima liječenja
HRP20140214T1 (hr) Derivati tetrahidrokinolina za lijeäśenje posttraumatskog stresnog poremeä†aja
RU2019114954A (ru) Способы применения индазол-3-карбоксамидов и их применение в качестве ингибиторов сигнального пути wnt/в-катенина
JP2016506387A5 (ru)
HRP20151399T1 (hr) Kinazni inhibitor koji regulira signalni put apoptoze
HRP20171028T1 (hr) Indolski i indazolski spojevi koji aktiviraju ampk
RU2017127135A (ru) Терапевтическое средство против рака желчных протоков
RU2015107803A (ru) Производные дигидроксипиримидинкарбоновой кислоты и их применение в лечении, облегчении или предотвращении вирусного заболевания
RU2010128512A (ru) Гетероциклические ингибиторы мек и способы их применения
PH12020550921A1 (en) Cap-dependent endonuclease inhibitors
RU2017116196A (ru) 2-амино-6-(дифторметил)-5,5-дифтор-6-фенил-3,4,5,6-тетрагидропиридины как ингибиторы васе1
HRP20100541T1 (hr) Derivati bifeniloksioctene kiseline za liječenje respiratornih bolesti
RU2010144637A (ru) Замещенные гамма-лактамы в качестве терапевтических агентов
RU2008100606A (ru) Ингибиторы сфингозинкиназы
HRP20130738T1 (hr) Postupak lijeäśenja ili profilakse
RU2009148673A (ru) Производные пиразинона и их применение для лечения легочных заболеваний
JP2014530900A5 (ru)
JP2009522292A5 (ru)
NZ593030A (en) Pyridyloxyindoles inhibitors of vegf-r2 and use thereof for treatment of disease
CO6150132A2 (es) 4-[4-({[4--cloro-3-(trifluorometil)fenil]carbamoil}amino)-3-fluorofenoxil]-n-metilpiridina-2-carboxamida monohidrato
JP2016503797A5 (ru)

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20150813