HRP20120900T1 - Inhibitori p38 kinaze bazirani na peteroäślanom heterociklu - Google Patents
Inhibitori p38 kinaze bazirani na peteroäślanom heterociklu Download PDFInfo
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- HRP20120900T1 HRP20120900T1 HRP20120900TT HRP20120900T HRP20120900T1 HR P20120900 T1 HRP20120900 T1 HR P20120900T1 HR P20120900T T HRP20120900T T HR P20120900TT HR P20120900 T HRP20120900 T HR P20120900T HR P20120900 T1 HRP20120900 T1 HR P20120900T1
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- 125000000623 heterocyclic group Chemical group 0.000 title abstract 2
- 229940043355 kinase inhibitor Drugs 0.000 title abstract 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract 8
- -1 2-dioxolanyl Chemical group 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 5
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 206010003246 arthritis Diseases 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 208000015181 infectious disease Diseases 0.000 claims 3
- 206010006895 Cachexia Diseases 0.000 claims 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims 2
- 201000005569 Gout Diseases 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 206010037660 Pyrexia Diseases 0.000 claims 2
- 206010040070 Septic Shock Diseases 0.000 claims 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 238000005755 formation reaction Methods 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- YKRHGHVJNYCHEN-UHFFFAOYSA-N 3-(5-amino-4-benzoylpyrazol-1-yl)-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1N(C=1N)N=CC=1C(=O)C1=CC=CC=C1 YKRHGHVJNYCHEN-UHFFFAOYSA-N 0.000 claims 1
- VGUSQKZDZHAAEE-UHFFFAOYSA-N 3-[5-amino-4-(3-cyanobenzoyl)pyrazol-1-yl]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1N(C=1N)N=CC=1C(=O)C1=CC=CC(C#N)=C1 VGUSQKZDZHAAEE-UHFFFAOYSA-N 0.000 claims 1
- 208000030507 AIDS Diseases 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
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- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010055128 Autoimmune neutropenia Diseases 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 208000004429 Bacillary Dysentery Diseases 0.000 claims 1
- 208000020084 Bone disease Diseases 0.000 claims 1
- 201000006474 Brain Ischemia Diseases 0.000 claims 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims 1
- 208000006029 Cardiomegaly Diseases 0.000 claims 1
- 206010008120 Cerebral ischaemia Diseases 0.000 claims 1
- 206010063094 Cerebral malaria Diseases 0.000 claims 1
- 206010008909 Chronic Hepatitis Diseases 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 claims 1
- 206010012438 Dermatitis atopic Diseases 0.000 claims 1
- 208000037487 Endotoxemia Diseases 0.000 claims 1
- 206010018364 Glomerulonephritis Diseases 0.000 claims 1
- 208000003807 Graves Disease Diseases 0.000 claims 1
- 208000015023 Graves' disease Diseases 0.000 claims 1
- 208000031886 HIV Infections Diseases 0.000 claims 1
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- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims 1
- 208000005176 Hepatitis C Diseases 0.000 claims 1
- 206010019755 Hepatitis chronic active Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 206010021143 Hypoxia Diseases 0.000 claims 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims 1
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- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 1
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- 230000001154 acute effect Effects 0.000 claims 1
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- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
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- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
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- 239000012453 solvate Substances 0.000 claims 1
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- 125000001424 substituent group Chemical group 0.000 claims 1
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- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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Claims (4)
1. Spoj, naznačen time, da ima formulu (I):
[image]
gdje:
C je pirazol-prsten ili imidazol-prsten;
A je aril-prsten;
B je aril-prsten;
D je -C(O)NR80R81, pri čemu su svaki od R80 i R81 međusobno neovisno vodik, cikloalkil ili alkoksi;
R1 je H ili acil;
R2 je H ili alkil;
R3 je vodik, 2-dioksolanil, pirimidinil, piridil, pirazinil, cijano, oksadiazolil, triazolil, metiltio, metansulfonil, 5-metiloksadiazolil, metil, CHO, jodo, kloro, metoksi, benziloksi, etoksi, ciklopropoksi, t-butoksikarbonilbutoksi ili karbamoilmetoksi;
R4 je vodik;
R5 je alkil; i
R6 je vodik,
ili njegov farmaceutski prihvatljiv derivat, koji je njegova sol, njegov solvat ili hidrat;
za uporabu u postupku liječenja stanja povezanih s p38, odabranih iz skupine koju čine pankreatitis (akutni ili kronični), astma, alergije, sindrom zastoja dišnog sustava kod odraslih, kronična opstrukcijska plućna bolest, glomerulonefritis, reumatoidni artritis, sistemski eritemski lupus, skleroderma, kronični tiroiditis, Grave-ova bolest, autoimuni gastritis, dijabetes, autoimuna hemolitička anemija, autoimuna neutropenija, trombocitopenija, atopični dermatitis, kronični aktivni hepatitis, miastenija gravis, multipla skleroza, upalna bolest crijeva, ulcerativni kolitis, Chron-ova bolest, psorijaza, bolest kada stanica domaćina odbacuje presadak, upalna reakcija potaknuta endotoksinom, tuberkuloza, ateroskleroza, mišićna degeneracija, kaheksija, psorijatični artritis, Reiter-ov sindrom, giht, traumatski artritis, rubeola artritis, akutni sinovitis, bolest β-stanica gušterače; bolesti koje karakterizira masivna infiltracija neutrofila; reumatoidni spondilitis; artritis kod gihta i ostala stanja kod artritisa; cerebralna malarija; kronična upalna plućna bolest, silikoza, plućna sarkoidoza, bolest resorpcije kostiju, odbijanja transplantata, groznica i mialgija zbog infekcije, kaheksija kao sekundarna bolest nakon infekcije, meloidne tvorbe, tvorbe oko tkiva kod ožiljka, ulcerativni kolitis, pireksija, gripa, osteoporoza, osteoartritis i koštani poremećaj povezan s multiple mijelomom, akutna mijelogena leukemija, kronična mijelogena leukemija, metastazni melanom, Kaposi-jev sarkom, multiple mijelom, sepsa, septički šok, i Šigeloza; Alzheimer-ova bolest, Parkinson-ova bolest, cerebralna ishemija ili neurodegenerativna bolest uzrokovana traumatskom ozljedom; angiogenski poremećaj uključujući čvrste tumore, očna neovaskulizacija, i dječji hemangiomi; virusne bolesti uključujući akutnu hepatitis infekciju (uključujući hepatitis A, hepatitis B i hepatitis C), HIV infekcija i CMV retinitis, AIDS, SARS, ARC ili zloćudne tvorbe, i herpes; udar, miokardijalna ishemija, ishemija napada srčanog udara, hipoksija organa, vaskularna hiperplazija, kardijska i renalna reperfuzijska ozljeda, tromboza, kardijska hipertrofija, agregacija krvnih pločica potaknuta trombinom, endotoksemija i/ili sindrom toksičnog šoka, i stanja povezana sa sintezom-2 endoperoksidaze prostaglandina.
2. Spoj formule I ili njegov farmaceutski prihvatljiv derivat za uporabu prema zahtjevu 1, naznačen time, da C je pirazol-prsten i preostali supstituenti određeni u zahtjevu 1.
3. Spoj formule I, naznačen time, da je to spoj 3-(5-amino-4-benzoil-pirazol-1-il)-N-ciklopropil-4-metil-benzamid, ili njegov farmaceutski prihvatljiv derivat određen u zahtjevu 1, te da je za uporabu prema zahtjevu 1.
4. Spoj formule I, naznačen time, da je to spoj 3-[5-amino-4-(3-cijanobenzoil)-pirazol-1-il]-N-ciklopropil-4-metil-benzamid, ili njegov farmaceutski prihvatljiv derivat određen u zahtjevu 1, te da je za uporabu prema zahtjevu 1.
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