HRP20180303T1 - Supstituirani 2-azabicikli i njihova uporaba kao modulatora receptora oreksina - Google Patents
Supstituirani 2-azabicikli i njihova uporaba kao modulatora receptora oreksina Download PDFInfo
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- HRP20180303T1 HRP20180303T1 HRP20180303TT HRP20180303T HRP20180303T1 HR P20180303 T1 HRP20180303 T1 HR P20180303T1 HR P20180303T T HRP20180303T T HR P20180303TT HR P20180303 T HRP20180303 T HR P20180303T HR P20180303 T1 HRP20180303 T1 HR P20180303T1
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- 108050000742 Orexin Receptor Proteins 0.000 title 1
- 102000008834 Orexin receptor Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 30
- 125000005843 halogen group Chemical group 0.000 claims 21
- 125000000217 alkyl group Chemical group 0.000 claims 20
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 13
- 125000004076 pyridyl group Chemical group 0.000 claims 13
- 125000002098 pyridazinyl group Chemical group 0.000 claims 12
- 125000003545 alkoxy group Chemical group 0.000 claims 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 9
- 125000000335 thiazolyl group Chemical group 0.000 claims 9
- 125000001425 triazolyl group Chemical group 0.000 claims 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims 8
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 8
- 125000002971 oxazolyl group Chemical group 0.000 claims 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims 8
- 208000035475 disorder Diseases 0.000 claims 7
- 201000010099 disease Diseases 0.000 claims 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims 6
- 208000020685 sleep-wake disease Diseases 0.000 claims 6
- 208000019116 sleep disease Diseases 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 208000012902 Nervous system disease Diseases 0.000 claims 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims 4
- 230000000155 isotopic effect Effects 0.000 claims 3
- 208000030159 metabolic disease Diseases 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 239000012453 solvate Substances 0.000 claims 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims 2
- 208000019022 Mood disease Diseases 0.000 claims 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- 208000019906 panic disease Diseases 0.000 claims 2
- 201000009032 substance abuse Diseases 0.000 claims 2
- 231100000736 substance abuse Toxicity 0.000 claims 2
- 208000011117 substance-related disease Diseases 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 208000019901 Anxiety disease Diseases 0.000 claims 1
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 206010012218 Delirium Diseases 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- 206010012735 Diarrhoea Diseases 0.000 claims 1
- 208000000059 Dyspnea Diseases 0.000 claims 1
- 206010013975 Dyspnoeas Diseases 0.000 claims 1
- 208000010496 Heart Arrest Diseases 0.000 claims 1
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010022489 Insulin Resistance Diseases 0.000 claims 1
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010033307 Overweight Diseases 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000005793 Restless legs syndrome Diseases 0.000 claims 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims 1
- 208000001871 Tachycardia Diseases 0.000 claims 1
- 208000000323 Tourette Syndrome Diseases 0.000 claims 1
- 208000016620 Tourette disease Diseases 0.000 claims 1
- 206010046996 Varicose vein Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 230000036506 anxiety Effects 0.000 claims 1
- 206010003119 arrhythmia Diseases 0.000 claims 1
- 230000006793 arrhythmia Effects 0.000 claims 1
- 206010007776 catatonia Diseases 0.000 claims 1
- 201000001883 cholelithiasis Diseases 0.000 claims 1
- 208000010877 cognitive disease Diseases 0.000 claims 1
- 230000001149 cognitive effect Effects 0.000 claims 1
- 230000007812 deficiency Effects 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 208000001130 gallstones Diseases 0.000 claims 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims 1
- -1 imidazothiazolyl Chemical group 0.000 claims 1
- 208000000509 infertility Diseases 0.000 claims 1
- 230000036512 infertility Effects 0.000 claims 1
- 231100000535 infertility Toxicity 0.000 claims 1
- 206010022437 insomnia Diseases 0.000 claims 1
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 201000008482 osteoarthritis Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000028173 post-traumatic stress disease Diseases 0.000 claims 1
- 208000013220 shortness of breath Diseases 0.000 claims 1
- 201000002859 sleep apnea Diseases 0.000 claims 1
- 230000006794 tachycardia Effects 0.000 claims 1
- 125000004385 trihaloalkyl group Chemical group 0.000 claims 1
- 208000027185 varicose disease Diseases 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- 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
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- 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
- C07D403/14—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 three or more hetero rings
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- 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
- C07D405/14—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 three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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Claims (30)
1. Spoj formule I
[image]
ili njegov enantiomer, dijastereomer, tautomer ili izotopska varijanta;
ili njegova farmaceutski prihvatljiva sol ili solvat; naznačen time da
X je N ili CR1;
Y je N ili CR2;
R1 je H, alkoksi, halo, triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil ili pirazolil, pri čemu triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil ili pirazolil je proizvoljno supstituiran s do dva supstituenta odabrana iz skupine koju čine halo i alkil;
R2 je H, alkil, alkoksi, ili halo;
Z je NH, N-CH3, N-CH2CH3, N-CH2-ciklopropil, N-C(=O)CH3, N-CH2CH2OCH3 ili O;
R3 je H, alkil, alkoksi, halo, triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil ili pirazolil, pri čemu triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil ili pirazolil je proizvoljnosupstituiran s do dva supstituenta odabrana iz skupine koju čine halo i alkil;
R4 je H ili alkil; ili
R3 i R4, zajedno sa atomima za koje su vezani, obrazuje 6-člani aril prsten ili 5-11 i 6-člani heteroaril prsten;
R5 je fenil, piridil, pirazinil, benzoksazolil, piridazinil, naftiridinil ili pirimidinil, pri čemu piridil, pirazinil, benzoksazolil, piridazinil, naftiridinil ili pirimidinil je proizvoljno supstituiran s do dvije skupine odabrane iz skupine koju čine halo, alkoksi, hidroksimetil i alkil; i
n je 1 ili 2,
pri čemu "alkil" je alkil skupina ravnog ili razgranatog lanca koja ima od 1 do 12 ugljikovih atoma u lancu ili monociklička, nearomatska skupina ugljikovodika koja ima od 3 do 7 ugljikovih atoma i proizvoljno supstituirana sa jednim ili više atoma halogena.
2. Spoj formule IA:
[image]
ili njegov enantiomer, dijastereomer, tautomer ili izotopska varijanta;
ili njegova farmaceutski prihvatljiva sol ili solvat; naznačen time da
prsten A je heteroaril prsten odabran iz skupine koju čine furanil, tiazolil, imidazotiazolil i pirazinil;
R1 je H, alkoksi, halo, triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil, ili pirazolil, pri čemu triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil ili pirazolil je proizvoljno supstituiran s do dva supstituenta odabrana iz skupine koju čine halo i alkil;
R2je H, alkil, alkoksi, ili halo;
Z je NH, N-CH3, N-CH2CH3, N-CH2-ciklopropil, N-C(=O)CH3, N-CH2CH2OCH3 ili O;
R3 je H, alkil, alkoksi, halo, triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil, ili pirazolil, pri čemu triazolil, tiazolil, piridazinil, pirimidinil, oksazolil, izoksazolil, oksadiazolil, piridil, fenil ili pirazolil je proizvoljno supstituiran s do dva supstituenta odabrana iz skupine koju čine halo i alkil;
R4 je H ili alkil;
ili R3 i R4, zajedno sa atomima za koje su vezani, obrazuje 6-člani aril prsten ili 5-ili 6-člani heteroaril prsten;
R5 je piridil, pirazinil, benzoksazolil, piridazinil, naftiridinil ili pirimidinil, pri čemu piridil, pirazinil, benzoksazolil, piridazinil, naftiridinil ili pirimidinil je proizvoljno supstituiran s do dva supstituenta odabrana iz skupine koju čine halo, alkoksi, hidroksimetil i alkil; i
n je 1 ili 2,
pri čemu "alkil" je alkil skupina ravnog ili razgranatog lanca koja ima od 1 do 12 ugljikovih atoma u lancu ili monociklička, nearomatska skupina ugljikovodika koja ima od 3 do 7 ugljikovih atoma i proizvoljno supstituirana s jednim ili više atoma halogena.
3. Spoj prema zahtjevu 1, naznačen time da
(i) X je CR1 i Y je CR2,
(ii) X je CR1 i Y je N, ili
(iii) X je N i Y je CR2.
4. Spoj prema bilo kojem od zahtjeva 1 do 3, naznačen time da Z je NH ili O.
5. Spoj prema bilo kojem od zahtjeva 1 do 4, naznačen time da R1 je alkoksi, halo, triazolil, ili pirimidinil.
6. Spoj prema bilo kojem od zahtjeva 1 do 5, naznačen time da R2 je H ili halo.
7. Spoj prema zahtjevu 6, naznačen time da halo je F.
8. Spoj prema bilo kojem od zahtjeva, naznačen time da R3 je H ili halo.
9. Spoj prema bilo kojem od prethodnih zahtjeva, naznačen time da R4 je H.
10. Spoj prema bilo kojem od prethodnih zahtjeva, naznačen time da R5 je piridil, proizvoljno supstituiran s halo ili alkil, ili pirazinil, proizvoljno supstituiran s halo ili alkil.
11. Spoj prema bilo kojem od zahtjeva 1 do 9, naznačen time da R5 je pirimidinil, proizvoljno supstituiran s halo ili alkil.
12. Spoj prema zahtjevu 11, naznačen time da navedeni alkil je trihaloalkil.
13. Spoj prema bilo kojem od zahtjeva, naznačen time da nje 1.
14. Spoj prema zahtjevu 1, naznačen time daje odabran iz skupine koju čine
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15. Spoj prema zahtjevu 1 naznačen time da je
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16. Spoj prema zahtjevu 1 naznačen time da je
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17. Spoj prema zahtjevu 1 naznačen time da je
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18. Spoj prema zahtjevu 1 naznačen time da je
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19. Spoj prema zahtjevu 1 naznačen time da je
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20. Spoj prema zahtjevu 2 naznačen time da je
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21. Enantiomer, dijastereoizomer, tautomer, izotopska varijanta, ili farmaceutski prihvatljiva sol ili solvat spoja prema bilo kojem od zahtjeva 14-20.
22. Farmaceutski pripravak naznačen time da sadrži terapeutski učinkovitu količinu spoja prema bilo kojem od prethodnih zahtjeva i barem jedno farmaceutski prihvatljivo pomoćno sredstvo.
23. Spoj prema bilo kojem od zahtjeva 1 do 21 naznačen time daje za upotrebu za liječenje bolesti, poremećaja ili medicinskog stanja, u kojem je bolest, poremećaj ili medicinsko stanje poremećaj spavanja, metabolički poremećaj, neurološki poremećaj, aritmija, akutni prestanak rada srca, sindrom iritabilnih crijeva, proljev, gastroezofagusni refluks, poremećaj raspoloženja, poremećaj posttraumatskog stresa, panični poremećaj, poremećaj nedostatka pažnje, kognitivna deficijencija, ili zloupotreba tvari.
24. Spoj za uporabu prema zahtjevu 23, naznačen time da bolest, poremećaj ili medicinsko stanje je poremećaj raspoloženja, posttraumatski poremećaj, panični poremećaj, poremećaj nedostatka pažnje, kognitivna deficijencija ili zloupotreba tvari.
25. Spoj za uporabu prema zahtjevu 23, naznačen time da bolest, poremećaj ili medicinsko stanje je poremećaj spavanja.
26. Spoj za uporabu prema zahtjevu 25, naznačen time da je poremećaj spavanja poremećaj prelaska iz sna u budnost, nesanica, sindrom nemirnih nogu, jet-lag, poremećaj spavanja, ili sekundarni poremećaj spavanja u vezi s neurološkim poremećajima.
27. Spoj za uporabu prema zahtjevu 23, naznačen time daje bolest, poremećaj ili medicinsko stanje metabolički poremećaj.
28. Spoj za uporabu prema zahtjevu 27, naznačen time da je metabolički poremećaj prekomjerna težina, gojaznost, otpornost na inzulin, dijabetes tipa II, hiperlipidemija, žučni kamenac, angina, hipertenzija, kratak dah, tahikardija, neplodnost, apneja u snu, bol u leđima i zglobovima, proširene vene, ili osteoartritis.
29. Spoj za uporabu prema zahtjevu 23, naznačen time da je bolest, poremećaj ili medicinsko stanje neurološki poremećaj.
30. Spoj za uporabu prema zahtjevu 29, naznačen time da je neurološki poremećaj Parkinsonova bolest, Alzheimerova bolest, Touretteov sindrom, katatonija, anksioznost, delirij ili demencija.
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Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA022766B1 (ru) | 2009-10-23 | 2016-02-29 | Янссен Фармацевтика Нв | ДВУЗАМЕЩЕННЫЕ ОКТАГИДРОПИРРОЛ[3,4-c]ПИРРОЛЫ В КАЧЕСТВЕ МОДУЛЯТОРОВ ОРЕКСИНОВЫХ РЕЦЕПТОРОВ |
| WO2011090738A2 (en) | 2009-12-29 | 2011-07-28 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| JP6106685B2 (ja) | 2011-11-17 | 2017-04-05 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | Ｃ−ｊｕｎ−ｎ−末端キナーゼ（ｊｎｋ）の阻害剤 |
| TWI621618B (zh) * | 2013-03-13 | 2018-04-21 | 比利時商健生藥品公司 | 經取代２－氮雜雙環類及其作為食慾素受體調控劑之用途 |
| TW201444849A (zh) | 2013-03-13 | 2014-12-01 | Janssen Pharmaceutica Nv | 經取代的7-氮雜雙環類及其作為食慾激素受體調節劑之用途 |
| TW201444821A (zh) | 2013-03-13 | 2014-12-01 | Janssen Pharmaceutica Nv | 經取代之哌啶化合物及其作為食慾素受體調節劑之用途 |
| MX2016011549A (es) * | 2014-03-06 | 2017-05-08 | Shanghai Haiyan Pharmaceutical Tech Co Ltd | Derivados de piperidina como antagonistas de receptores de orexina. |
| JP6715239B2 (ja) * | 2014-09-11 | 2020-07-01 | ヤンセン ファーマシューティカ エヌ．ベー． | 置換２−アザ二環式化合物及びオレキシン受容体調節因子としてのその使用 |
| WO2016100157A2 (en) * | 2014-12-19 | 2016-06-23 | Merck Sharp & Dohme Corp. | 6,5-bicyclic octahydropyrrolopyridine orexin receptor antagonists |
| EP3236959A4 (en) | 2014-12-23 | 2018-04-25 | Dana Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
| CN106349228B (zh) | 2015-07-17 | 2019-07-09 | 广东东阳光药业有限公司 | 取代的喹唑啉酮类化合物及其制备方法和用途 |
| WO2017028732A1 (zh) * | 2015-08-14 | 2017-02-23 | 上海海雁医药科技有限公司 | 食欲素受体拮抗剂化合物的晶型及其制备方法和应用 |
| EP4019515A1 (en) | 2015-09-09 | 2022-06-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
| US10370380B2 (en) | 2015-11-23 | 2019-08-06 | Sunshine Lake Pharma Co., Ltd. | Octahydropyrrolo[3,4-c]pyrrole derivatives and uses thereof |
| KR20230116948A (ko) | 2016-03-10 | 2023-08-04 | 얀센 파마슈티카 엔.브이. | 오렉신-2 수용체 길항제를 사용한 우울증의 치료 방법 |
| CA2968836A1 (en) | 2016-06-13 | 2017-12-13 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| EP3468962A1 (en) | 2016-06-13 | 2019-04-17 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| CA3041563C (en) | 2016-11-22 | 2023-10-31 | Dana-Farber Cancer Institute, Inc. | Pyrimidin-2-amine derivatives and pharmaceutical compositions thereof useful as inhibitors of cyclin-dependent kinase 12 (cdk12) |
| PT4122464T (pt) | 2017-03-28 | 2024-06-27 | Gilead Sciences Inc | Combinações terapêuticas para o tratamento de doenças do fígado |
| GB2558975B (en) * | 2017-09-01 | 2019-01-23 | Chronos Therapeutics Ltd | Substituted 2-azabicyclo[3.1.1]heptane and 2-azabicyclo[3.2.1]octane derivatives as orexin receptor antagonists |
| CN111315734B (zh) * | 2017-09-01 | 2024-03-08 | 克罗诺斯治疗有限公司 | 作为食欲素受体拮抗剂的经取代的2-氮杂双环[3.1.1]庚烷和2-氮杂双环[3.2.1]辛烷衍生物 |
| AU2019295632B2 (en) | 2018-06-25 | 2025-03-06 | Dana-Farber Cancer Institute, Inc. | Taire family kinase inhibitors and uses thereof |
| WO2020123925A1 (en) * | 2018-12-14 | 2020-06-18 | Dana-Farber Cancer Institute, Inc. | Pyrazolopyridine inhibitors of c-jun-n-terminal kinases and uses thereof |
| IL284591B1 (en) | 2019-01-15 | 2024-12-01 | Gilead Sciences Inc | Fxr (nr1h4) modulating compounds |
| CN118388473A (zh) | 2019-02-19 | 2024-07-26 | 吉利德科学公司 | Fxr激动剂的固体形式 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3674793A (en) | 1967-03-29 | 1972-07-04 | Sterling Drug Inc | 6-hydroxy-2-azabicyclo(2.2.2)octan-3-ones and 2-azabicyclo(2.2.2.)octane-3,6-diones |
| US6505492B2 (en) | 2001-04-11 | 2003-01-14 | Bethlehem Steel Corporation | Method and apparatus for forming deep-drawn articles |
| WO2002094790A1 (fr) | 2001-05-23 | 2002-11-28 | Mitsubishi Pharma Corporation | Compose heterocyclique condense et son utilisation medicale |
| AU2003202753A1 (en) | 2003-02-07 | 2004-08-30 | Ranbaxy Laboratories Limited | Oxazolidinone derivatives as antimicrobials |
| JP2006518367A (ja) | 2003-02-21 | 2006-08-10 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | エキソ−（ｔ−ブチル２Ｒ（＋））−２−アミノ−７−アザビシクロ［２．２．１］ヘプタン−７−カルボキシレート、中間体、およびそれらを製造および単離する方法 |
| AU2006329007A1 (en) | 2005-12-20 | 2007-06-28 | Novartis Ag | Nicotinic acid derivatives as modulators of metabotropic glutamate receptors |
| EP2272509A1 (en) | 2006-09-11 | 2011-01-12 | Novartis AG | New Uses of metabotropic glutamate receptors |
| EP2094685B1 (en) | 2006-12-01 | 2011-01-19 | Actelion Pharmaceuticals Ltd. | 3-heteroaryl (amino or amido)-1- (biphenyl or phenylthiazolyl) carbonylpiperdine derivatives as orexin receptor inhibitors |
| AR064561A1 (es) | 2006-12-28 | 2009-04-08 | Actelion Pharmaceuticals Ltd | Derivados de 2-aza-biciclo[3.1.0]hexano y su uso en la preparacion de un medicamento para el tratamiento de enfermedades relacionadas con disfunciones generales del sistema de la orexina. |
| AU2008260647A1 (en) * | 2007-05-23 | 2008-12-11 | Merck Sharp & Dohme Corp. | Cyclopropyl pyrrolidine orexin receptor antagonists |
| SI2170864T1 (sl) | 2007-07-17 | 2012-04-30 | Bristol Myers Squibb Co | Piridon gpr119g proteinsko povezani receptorski antagonisti |
| AU2008340421B2 (en) | 2007-12-21 | 2013-12-19 | F. Hoffmann-La Roche Ag | Heteroaryl derivatives as orexin receptor antagonists |
| NZ588080A (en) * | 2008-02-21 | 2012-04-27 | Actelion Pharmaceuticals Ltd | 2-Aza-bicyclo[2.2.1]heptane derivatives |
| JP2011519849A (ja) | 2008-04-30 | 2011-07-14 | アクテリオン ファーマシューティカルズ リミテッド | ピペリジン及びピロリジン化合物 |
| AU2009270971A1 (en) | 2008-07-16 | 2010-01-21 | Schering Corporation | Bicyclic Heterocycle Derivatives and use thereof as GPR119 modulators |
| CA2739916A1 (en) | 2008-10-21 | 2010-04-29 | Merck Sharp & Dohme Corp. | 2,5-disubstituted piperidine orexin receptor antagonists |
| WO2010048016A1 (en) | 2008-10-21 | 2010-04-29 | Merck Sharp & Dohme Corp. | 2,3-disubstituted piperidine orexin receptor antagonists |
| EA201170742A1 (ru) | 2008-12-02 | 2012-01-30 | Глэксо Груп Лимитед | Производные n-{[(1r,4s,6r)-3-(2-пиридинилкарбонил)-3-азабицикло[4.1.0]гепт-4-ил]метил}-2-гетероариламинов и их применения |
| AR076024A1 (es) | 2009-04-03 | 2011-05-11 | Schering Corp | Derivados de heterociclos biciclicos puenteados y metodos de uso de los mismos |
| BRPI1013933A2 (pt) | 2009-04-24 | 2017-06-13 | Glaxo Group Ltd | 3-azabiciclo [4.1.0] heptanos usados como antagonistas de orexina |
| JP5847087B2 (ja) * | 2009-10-23 | 2016-01-20 | ヤンセン ファーマシューティカ エヌ．ベー． | オレキシン受容体調節因子としての縮合複素環式化合物 |
| WO2011050202A1 (en) | 2009-10-23 | 2011-04-28 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as orexin receptor modulators |
| EA022766B1 (ru) | 2009-10-23 | 2016-02-29 | Янссен Фармацевтика Нв | ДВУЗАМЕЩЕННЫЕ ОКТАГИДРОПИРРОЛ[3,4-c]ПИРРОЛЫ В КАЧЕСТВЕ МОДУЛЯТОРОВ ОРЕКСИНОВЫХ РЕЦЕПТОРОВ |
| EP2493307B1 (en) | 2009-10-29 | 2016-04-27 | Merck Sharp & Dohme Corp. | Bridged bicyclic piperidine derivatives and methods of use thereof |
| EP2503887B1 (en) | 2009-11-24 | 2016-01-06 | Merck Sharp & Dohme Corp. | Substituted biaryl derivatives and methods of use thereof |
| AU2010332010A1 (en) | 2009-12-14 | 2012-08-02 | Inspire Pharmaceuticals, Inc. | Bridged bicyclic Rho kinase inhibitor compounds, composition and use |
| US8697691B2 (en) | 2009-12-21 | 2014-04-15 | Vanderbilt University | Alkyl 3-((2-amidoethyl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate analogs as selective M1 agonists and methods of making and using same |
| UY33227A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
| WO2011159657A1 (en) | 2010-06-18 | 2011-12-22 | Merck Sharp & Dohme Corp. | Bicyclic heterocycle derivatives and methods of use thereof |
| WO2012089606A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Azabicyclo [4.1.0] hept - 4 - yl derivatives as human orexin receptor antagonists |
| US9586962B2 (en) | 2011-04-20 | 2017-03-07 | Janssen Pharmaceutica Nv | Disubstituted octahydropyrrolo [3,4-C] pyrroles as orexin receptor modulators |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| WO2014066196A1 (en) | 2012-10-23 | 2014-05-01 | Merck Sharp & Dohme Corp. | 2-pyridyloxy-3-substituted-4-nitrile orexin receptor antagonists |
| MX2015006191A (es) | 2012-11-16 | 2015-08-10 | Merck Sharp & Dohme | Inhibidores de purina de fosfatidilinositol 3-quinasa delta humana. |
| TW201444849A (zh) | 2013-03-13 | 2014-12-01 | Janssen Pharmaceutica Nv | 經取代的7-氮雜雙環類及其作為食慾激素受體調節劑之用途 |
| TWI621618B (zh) | 2013-03-13 | 2018-04-21 | 比利時商健生藥品公司 | 經取代２－氮雜雙環類及其作為食慾素受體調控劑之用途 |
| CN106458985B (zh) | 2014-02-06 | 2019-05-03 | 艾伯维公司 | 6-杂芳氧基-和6-芳氧基-喹啉-2-甲酰胺及其用途 |
| JP6715239B2 (ja) | 2014-09-11 | 2020-07-01 | ヤンセン ファーマシューティカ エヌ．ベー． | 置換２−アザ二環式化合物及びオレキシン受容体調節因子としてのその使用 |
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