HRP20090512T1 - Derivati pirolopiridina i njihova upotreba kao modulatora ppar receptora - Google Patents
Derivati pirolopiridina i njihova upotreba kao modulatora ppar receptora Download PDFInfo
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- HRP20090512T1 HRP20090512T1 HR20090512T HRP20090512T HRP20090512T1 HR P20090512 T1 HRP20090512 T1 HR P20090512T1 HR 20090512 T HR20090512 T HR 20090512T HR P20090512 T HRP20090512 T HR P20090512T HR P20090512 T1 HRP20090512 T1 HR P20090512T1
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- 150000005255 pyrrolopyridines Chemical class 0.000 title abstract 3
- 101150014691 PPARA gene Proteins 0.000 title 1
- -1 3,4-dihydro-1,4-benzoxazinyl Chemical group 0.000 claims abstract 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 6
- 125000003118 aryl group Chemical group 0.000 claims abstract 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims abstract 5
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 5
- 125000001624 naphthyl group Chemical group 0.000 claims abstract 5
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims abstract 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims 25
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 8
- 125000004076 pyridyl group Chemical group 0.000 claims 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
- 125000002971 oxazolyl group Chemical group 0.000 claims 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims 7
- 125000000335 thiazolyl group Chemical group 0.000 claims 7
- 239000007858 starting material Substances 0.000 claims 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- 125000005843 halogen group Chemical group 0.000 claims 5
- 239000002904 solvent Substances 0.000 claims 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 4
- 125000003277 amino group Chemical group 0.000 claims 4
- 235000010290 biphenyl Nutrition 0.000 claims 4
- 239000004305 biphenyl Substances 0.000 claims 4
- 238000006243 chemical reaction Methods 0.000 claims 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims 4
- 125000006393 methylpyrimidinyl group Chemical group 0.000 claims 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 4
- 125000005493 quinolyl group Chemical group 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 229910052801 chlorine Inorganic materials 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000002541 furyl group Chemical group 0.000 claims 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims 3
- 125000001544 thienyl group Chemical group 0.000 claims 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 238000010306 acid treatment Methods 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims 2
- 125000004185 ester group Chemical group 0.000 claims 2
- 230000007062 hydrolysis Effects 0.000 claims 2
- 238000006460 hydrolysis reaction Methods 0.000 claims 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 2
- 229910052740 iodine Inorganic materials 0.000 claims 2
- 239000011707 mineral Substances 0.000 claims 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims 1
- 208000032928 Dyslipidaemia Diseases 0.000 claims 1
- 206010048554 Endothelial dysfunction Diseases 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 1
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
- 206010022489 Insulin Resistance Diseases 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 claims 1
- 150000000475 acetylene derivatives Chemical class 0.000 claims 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims 1
- PPDJNZTUDFPAHX-UHFFFAOYSA-N benzyltrimethylammonium dichloroiodate Chemical compound Cl[I-]Cl.C[N+](C)(C)CC1=CC=CC=C1 PPDJNZTUDFPAHX-UHFFFAOYSA-N 0.000 claims 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000000460 chlorine Chemical group 0.000 claims 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 230000008694 endothelial dysfunction Effects 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 230000002140 halogenating effect Effects 0.000 claims 1
- 238000005658 halogenation reaction Methods 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 238000006192 iodination reaction Methods 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 150000004944 pyrrolopyrimidines Chemical class 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 claims 1
- 229910000367 silver sulfate Inorganic materials 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract 3
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 abstract 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 abstract 2
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 abstract 1
- 208000001953 Hypotension Diseases 0.000 abstract 1
- 108010016731 PPAR gamma Proteins 0.000 abstract 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 abstract 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 abstract 1
- 239000012190 activator Substances 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 230000001539 anorectic effect Effects 0.000 abstract 1
- 230000002456 anti-arthritic effect Effects 0.000 abstract 1
- 230000003178 anti-diabetic effect Effects 0.000 abstract 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract 1
- 230000002402 anti-lipaemic effect Effects 0.000 abstract 1
- 230000000648 anti-parkinson Effects 0.000 abstract 1
- 230000003356 anti-rheumatic effect Effects 0.000 abstract 1
- 239000003472 antidiabetic agent Substances 0.000 abstract 1
- 239000000939 antiparkinson agent Substances 0.000 abstract 1
- 239000003435 antirheumatic agent Substances 0.000 abstract 1
- 206010061428 decreased appetite Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 208000021822 hypotensive Diseases 0.000 abstract 1
- 230000001077 hypotensive effect Effects 0.000 abstract 1
- 230000010534 mechanism of action Effects 0.000 abstract 1
- 230000000324 neuroprotective effect Effects 0.000 abstract 1
- 230000001777 nootropic effect Effects 0.000 abstract 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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Abstract
Novi derivati pirolopirimidina, naznačeni time što ih se bira izmeđui) spojeva formule: u kojoj: svaki od R1 i R2 neovisno predstavlja atom vodika, atom halogena, C1-C3 alkilnu ili C1-C4 alkoksi skupinu ili CF3 skupinu, svaki od R3 i R4 neovisno predstavlja atom vodika ili C1-C4 alkilnu skupinu, R predstavlja atom vodika ili C1-C3 alkilnu skupinu, n = 1, 2 ili 3, X predstavlja jednostruku vezu ili atom kisika, Ar predstavlja aromatski ili heteroaromatski prsten, kojeg se bira između fenilne, pirazolilne, imidazolilne, tiazolilne, oksazolilne, izoksazolilne, furilne, tienilne, pirolilne, piridilne, bifenilne, naftilne, 1,2,3,4-tetrahidronaftilne, kinolilne, izokinolilne, 1,2,3,4-tetrahidrokinolilne, benzimidazolilne, benzopirazinilne, indolilne, 2,3-dihidroindolilne, benzofurilne, 2,3-dihidrobenzofurilne, benzotiazolilne, benzotiadiazolilne, benzizoksazolilne, 3,4-dihidro-1,4-benzoksazinilne, 1,3-benzodioksolilne, 2,3-dihidrobenzodioksinilne, imidazotiazolilne i benzoksazolilne skupine, izborno supstituirane s jednim ili više (primjerice 2 ili 3) supstituenata, koje se bira između atoma halogena, C1-C6 alkilne, C1-C4 alkoksi, trifluormetilne, trifluormetoksi, nitro, acetilne, acetilamino, dialkilamino i amino skupine, ili oksazolilnog, tiazolilnog, pirazolilnog, pirolidinilnog, piridilnog, pirimidinilnog, metilpirimidinilnog ili morfolinilnog heterocikla, ii) njihovih farmaceutski prihvatljivih soli. Patent sadrži još 9 patentnih zahtjeva.
Claims (10)
1. Novi derivati pirolopirimidina, naznačeni time što ih se bira između
i) spojeva formule:
[image]
u kojoj:
svaki od R1 i R2 neovisno predstavlja atom vodika, atom halogena, C1-C3 alkilnu ili C1-C4 alkoksi skupinu ili CF3 skupinu,
svaki od R3 i R4 neovisno predstavlja atom vodika ili C1-C4 alkilnu skupinu,
R predstavlja atom vodika ili C1-C3 alkilnu skupinu,
n = 1, 2 ili 3,
X predstavlja jednostruku vezu ili atom kisika,
Ar predstavlja aromatski ili heteroaromatski prsten, kojeg se bira između fenilne, pirazolilne, imidazolilne, tiazolilne, oksazolilne, izoksazolilne, furilne, tienilne, pirolilne, piridilne, bifenilne, naftilne, 1,2,3,4-tetrahidronaftilne, kinolilne, izokinolilne, 1,2,3,4-tetrahidrokinolilne, benzimidazolilne, benzopirazinilne, indolilne, 2,3-dihidroindolilne, benzofurilne, 2,3-dihidrobenzofurilne, benzotiazolilne, benzotiadiazolilne, benzizoksazolilne, 3,4-dihidro-1,4-benzoksazinilne, 1,3-benzodioksolilne, 2,3-dihidrobenzodioksinilne, imidazotiazolilne i benzoksazolilne skupine, izborno supstituirane s jednim ili više (primjerice 2 ili 3) supstituenata, koje se bira između atoma halogena, C1-C6 alkilne, C1-C4 alkoksi, trifluormetilne, trifluormetoksi, nitro, acetilne, acetilamino, dialkilamino i amino skupine, ili oksazolilnog, tiazolilnog, pirazolilnog, pirolidinilnog, piridilnog, pirimidinilnog, metilpirimidinilnog ili morfolinilnog heterocikla,
ii) njihovih farmaceutski prihvatljivih soli.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što Ar predstavlja aromatski ili heteroaromatski prsten, kojeg se bira između fenilne, piridilne, bifenilne, naftilne, kinolilne, benzopirazinilne, indolilne, 2,3-dihidroindolilne, benzofurilne, 2,3-dihidrobenzofurilne, benzotiazolilne, benzotiadiazolilne, benzizoksazolilne, 3,4-dihidro-1,4-benzoksazinilne, 1,3-benzodioksolilne, 2,3-dihidrobenzodioksinilne, imidazotiazolilne i benzoksazolilne skupine izborno supstituirane s jednim ili više (primjerice 2 ili 3) supstituenata, koje se bira između atoma halogena i C1-C6 alkilne, C1-C4 alkoksi, trifluormetilne, trifluormetoksi, nitro, acetilne, acetilamino, dialkilamino i amino skupine, ili oksazolilnog, tiazolilnog, pirazolilnog, pirolidinilnog, piridilnog, pirimidinilnog, metilpirimidinilnog ili morfolinilog heterocikla.
3. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, naznačen time što R1 predstavlja atom klora ili trifluormetilnu skupinu.
4. Spoj u skladu s jednim od patentnih zahtjeva 1 do 3, namijenjen upotrebi kao farmakološki aktivna tvar.
5. Upotreba spoja u skladu s jednim od patentnih zahtjeva 1 do 3, u proizvodnji medikamenta za liječenje hipertrigliceridemije, hiperlipidemije, hiperkolesterolemije, dislipidemije, otpornosti na inzulin, dijabetesa i pretilosti.
6. Upotreba spoja u skladu s jednim od patentnih zahtjeva 1 do 3, u proizvodnji medikamenta za liječenje disfunkcije endotela.
7. Upotreba spoja u skladu s jednim od patentnih zahtjeva 1 do 3, u proizvodnji medikamenta za liječenje kardiovaskularnih bolesti, upalnih bolesti i neurodegenerativnih bolesti, osobito onih poput Alzheimerove bolesti ili Parkinsonove bolesti.
8. Farmaceutski pripravak, naznačen time što sadrži najmanje jedan spoj u skladu s jednim od patentnih zahtjeva 1 do 3 kao aktivnu tvar.
9. Postupak dobivanje spoja u skladu s patentnim zahtjevom 1, naznačen time što se sastoji u koracima:
a) provođenja reakcije halogeniranja, po mogućnosti reakcije jodiranja, amino piridina formule
[image]
u kojoj:
svaki od R1 i R2 neovisno predstavlja atom vodika, atom fluora, broma ili klora ili C1-C4 alkilnu, C1-C4 alkoksi ili trifluormetilnu skupinu,
sredstvom za halogeniranje, poput, primjerice, joda, u prisutnosti srebrnog sulfata ili benziltrimetilamonijevog diklorojodata, u otapalu, na sobnoj temperaturi, u trajanju od 5 do 24 sata, kako bi se dobilo spoj formule
[image]
u kojoj:
R1 i R2 imaju ista značenja kao u polaznim spojevima;
b) reakcije, i to Sonogashirine reakcije, spoja formule III s acetilenskim derivatom formule
[image]
u kojoj:
n = 1, 2 ili 3;
svaki od R3 i R4 neovisno predstavlja atom vodika ili C1-C4 alkilnu skupinu;
R predstavlja C1-C3 alkilnu skupinu;
X predstavlja jednostruku vezu ili atom kisika;
u prisutnosti bakrenog(I) jodida, paladijskog katalizatora, primjerice tetrakis(trifenilfosfin)paladija ili diklorbis(trifenilfosfin)paladija, te organske baze, u otapalu, na temperaturi između 0 i 60 °C, u trajanju od 2 do 24 sata, kako bi se dobilo spoj formule
[image]
u kojoj:
R1, R2, n, X, R3, R4 i R imaju ista značenja kao u polaznim spojevima;
c) reakcije spoja formule V s arilsulfonil-kloridom formule
[image]
u kojoj:
Ar predstavlja aromatski ili heteroaromatski prsten, kojeg se bira između fenilne, pirazolilne, imidazolilne, tiazolilne, oksazolilne, izoksazolilne, furilne, tienilne, pirolilne, piridilne, bifenilne, naftilne, 1,2,3,4-tetrahidronaftilne, kinolilne, izokinolilne, 1,2,3,4-tetrahidrokinolilne, benzimidazolilne, benzopirazinilne, indolilne, 2,3-dihidroindolilne, benzofurilne, 2,3-dihidrobenzofurilne, benzotiazolilne, benzotiadiazolilne, benzizoksazolilne, 3,4-dihidro-1,4-benzoksazinilne, 1,3-benzodioksolilne, 2,3-dihidrobenzodioksinilne, imidazotiazolilne i benzoksazolilne skupine, izborno supstituirane s jednim ili više (primjerice 2 ili 3) supstituenata, koje se bira između atoma halogena i C1-C6 alkilne, C1-C4 alkoksi, trifluormetilne, trifluormetoksi, nitro, acetilne, acetilamino, dialkilamino i amino skupine, ili oksazolilnog, tiazolilnog, pirazolilnog, pirolidinilnog, piridilnog, pirimidinilnog, metilpirimidinilnog ili morfolinilnog heterocikla,
u prisutnosti piridina, izborno u otapalu, na sobnoj temperaturi, u trajanju od 10 do 120 minuta, kako bi se dobilo spoj formule
[image]
u kojoj:
R1, R2, n, X, R3, R4, R i Ar imaju ista značenja kao u polaznim spojevima;
d) provođenja cikliziranja spoja formule VII, primjerice uz pomoć bakrenog(II) acetata, u otapalu, kako bi se dobilo spoj formule
[image]
u kojoj:
R1, R2, n, X, R3, R4, R i Ar imaju ista značenja kao u polaznim spojevima;
e) ako je to potrebno, hidrolize esterske funkcionalne skupine u spoju formule Ia, primjerice uz pomoć mineralne baze, kako bi se, obradom kiselinom, dobilo spoj formule I, u obliku slobodne kiseline:
[image]
10. Postupak dobivanje spoja u skladu s patentnim zahtjevom 1, naznačen time što se sastoji u koracima:
a) reakcije spoja formule (III)
[image]
u kojoj svaki od R1 i R2 neovisno predstavlja atom vodika, klora ili broma ili C1-C4 alkilnu, C1-C4 alkoksi ili trifluormetilnu skupinu,
s arilsulfonil-kloridom formule
[image]
u kojoj:
Ar predstavlja aromatski ili heteroaromatski prsten, kojeg se bira između fenilne, pirazolilne, imidazolilne, tiazolilne, oksazolilne, izoksazolilne, furilne, tienilne, pirolilne, piridilne, bifenilne, naftilne, 1,2,3,4-tetrahidronaftilne, kinolilne, izokinolilne, 1,2,3,4-tetrahidrokinolilne, benzimidazolilne, benzopirazinilne, indolilne, 2,3-dihidroindolilne, benzofurilne, 2,3-dihidrobenzofurilne, benzotiazolilne, benzotiadiazolilne, benzizoksazolilne, 3,4-dihidro-1,4-benzoksazinilne, 1,3-benzodioksolilne, 2,3-dihidrobenzodioksinilne, imidazotiazolilne i benzoksazolilne skupine, izborno supstituirane s jednim ili više (primjerice 2 ili 3) supstituenata, koje se bira između atoma halogena i C1-C6 alkilne, C1-C4 alkoksi, trifluormetilne, trifluormetoksi, nitro, acetilne, acetilamino, dialkilamino i amino skupine, ili oksazolilnog, tiazolilnog, pirazolilnog, pirolidinilnog, piridilnog, pirimidinilnog, metilpirimidinilnog ili morfolinilnog heterocikla,
u otapalu, na sobnoj temperaturi, u trajanju od 1 do 12 sati, kako bo se dobilo spoj formule (VIII)
[image]
u kojoj:
R1, R2 i Ar imaju ista značenja kao u polaznim spojevima;
b) reakcije spoja formule VIII s acetilenskim derivatom formule
[image]
u kojoj:
n = 1, 2 ili 3;
svaki od R3 i R4 neovisno predstavlja atom vodika ili C1-C4 alkilnu skupinu;
R predstavlja C1-C3 alkilnu skupinu;
X predstavlja jednostruku vezu ili atom kisika,
u uvjetima sličnim onima opisanim za korak b) postupka u skladu s patentnim zahtjevom 9, kako bi se dobilo spoj formule
[image]
u kojoj R1, R2, n, X, R3, R4, R i Ar imaju ista značenja kao u polaznim spojevima;
c) ako je to potrebno, hidrolize esterske funkcionalne skupine u spoju formule Ia, primjerice uz pomoć mineralne baze, kako bi se, obradom kiselinom, dobilo spoj formule I, u obliku slobodne kiseline:
[image]
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71345905P | 2005-09-01 | 2005-09-01 | |
| FR0510482A FR2890072A1 (fr) | 2005-09-01 | 2005-10-14 | Nouveaux composesde pyrrolopyridine |
| PCT/FR2006/050827 WO2007026104A1 (fr) | 2005-09-01 | 2006-08-31 | Derives de pyrrolopyridine et leurs utilisations comme modulateurs des recepteurs ppar |
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| Publication Number | Publication Date |
|---|---|
| HRP20090512T1 true HRP20090512T1 (hr) | 2009-12-31 |
Family
ID=37735036
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20090512T HRP20090512T1 (hr) | 2005-09-01 | 2009-09-25 | Derivati pirolopiridina i njihova upotreba kao modulatora ppar receptora |
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| Country | Link |
|---|---|
| US (2) | US7557122B2 (hr) |
| EP (1) | EP1919474B1 (hr) |
| JP (1) | JP5232000B2 (hr) |
| KR (1) | KR101289589B1 (hr) |
| CN (1) | CN101242833B (hr) |
| AT (1) | ATE438396T1 (hr) |
| AU (1) | AU2006286348B2 (hr) |
| BR (1) | BRPI0615335A2 (hr) |
| CA (1) | CA2620662C (hr) |
| DE (1) | DE602006008320D1 (hr) |
| DK (1) | DK1919474T3 (hr) |
| EA (1) | EA014185B1 (hr) |
| ES (1) | ES2331336T3 (hr) |
| FR (1) | FR2890072A1 (hr) |
| HK (1) | HK1116698A1 (hr) |
| HR (1) | HRP20090512T1 (hr) |
| IL (1) | IL189189A (hr) |
| MX (1) | MX2008003038A (hr) |
| MY (1) | MY142983A (hr) |
| NO (1) | NO340681B1 (hr) |
| PL (1) | PL1919474T3 (hr) |
| PT (1) | PT1919474E (hr) |
| SI (1) | SI1919474T1 (hr) |
| TN (1) | TNSN08091A1 (hr) |
| UA (1) | UA92026C2 (hr) |
| WO (1) | WO2007026104A1 (hr) |
| ZA (1) | ZA200801885B (hr) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2607670A1 (en) * | 2005-05-10 | 2006-11-16 | Vertex Pharmaceuticals Incorporated | Bicyclic derivatives as modulators of ion channels |
| FR2890071B1 (fr) * | 2005-08-30 | 2007-11-09 | Fournier Sa Sa Lab | Nouveaux composes de l'indole |
| PE20090159A1 (es) * | 2007-03-08 | 2009-02-21 | Plexxikon Inc | COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs |
| KR101156845B1 (ko) * | 2007-05-21 | 2012-06-18 | 에스지엑스 파마슈티컬스, 인코포레이티드 | 헤테로시클릭 키나제 조절제 |
| FR2955108B1 (fr) * | 2010-01-08 | 2012-03-16 | Fournier Lab Sa | Utilisation de derives de pyrrolopyridine comme activateurs de nurr-1, pour le traitement de la maladie de parkinson |
| FR2955110A1 (fr) * | 2010-01-08 | 2011-07-15 | Fournier Lab Sa | Nouveaux derives de type pyrrolopyridine benzoique |
| WO2013122897A1 (en) * | 2012-02-13 | 2013-08-22 | Amgen Inc. | Dihydrobenzoxazine and tetrahydroquinoxaline sodium channel inhibitors |
| WO2013134518A1 (en) | 2012-03-09 | 2013-09-12 | Amgen Inc. | Sulfamide sodium channel inhibitors |
| GB201317363D0 (en) * | 2013-10-01 | 2013-11-13 | Eisai Ltd | Novel compounds |
| CN103630519A (zh) * | 2013-12-03 | 2014-03-12 | 华东理工大学 | 应用pH敏感的比率荧光蛋白检测酶-前药反应的方法 |
| CN108164528B (zh) * | 2018-03-31 | 2019-03-22 | 杭州巴洛特生物科技有限公司 | 一种酰胺类衍生物及其在高血压、高血脂和动脉粥样硬化中的应用 |
| CN108456207B (zh) * | 2018-03-31 | 2020-11-20 | 浙江药苑生物科技有限公司 | 一种酰胺类衍生物及其在心脑血管方面的应用 |
| CN108383838B (zh) * | 2018-03-31 | 2020-08-28 | 浙江药苑生物科技有限公司 | 一种酰胺类衍生物及其在高血压、高血脂和动脉粥样硬化中的应用 |
| CN108218865B (zh) * | 2018-03-31 | 2020-06-26 | 济南市儿童医院 | 一种酰胺类衍生物及其在心脑血管方面的应用 |
| CN111793066B (zh) * | 2020-07-17 | 2022-04-08 | 瀚海新拓(杭州)生物医药有限公司 | 苯并五元杂环磺酰胺类化合物、其制备方法、药物组合物及应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU1856997A (en) | 1996-02-02 | 1997-08-22 | Merck & Co., Inc. | Method for raising hdl cholesterol levels |
| ES2184145T3 (es) | 1996-12-13 | 2003-04-01 | Aventis Pharma Inc | Compuestos de acido sulfonico o sulfonilamino-n-(heteroaralquil)-azaheterociclilamida. |
| AU784722B2 (en) | 2000-02-18 | 2006-06-01 | Merck & Co., Inc. | Aryloxyacetic acids for diabetes and lipid disorders |
| AU2002258550B2 (en) | 2001-03-14 | 2006-04-27 | Eli Lilly And Company | Retinoid X receptor modulators |
| CA2467542A1 (en) * | 2001-11-19 | 2003-05-30 | Neurogen Corporation | 1h-pyrrolo[3,2-b]pyridine-3-carboxylic acid amides |
| DE10229777A1 (de) * | 2002-07-03 | 2004-01-29 | Bayer Ag | Indolin-Phenylsulfonamid-Derivate |
| DE10300099A1 (de) | 2003-01-07 | 2004-07-15 | Bayer Healthcare Ag | Indol-Phenylsulfonamid-Derivate |
| US20050014753A1 (en) * | 2003-04-04 | 2005-01-20 | Irm Llc | Novel compounds and compositions as protein kinase inhibitors |
| NZ545326A (en) * | 2003-07-17 | 2009-12-24 | Plexxikon Inc | PPAR active compounds |
| DE10335449A1 (de) | 2003-08-02 | 2005-02-17 | Bayer Healthcare Ag | Bicyclische Indolinsulfonamid-Derivate |
| DE10335450A1 (de) | 2003-08-02 | 2005-02-17 | Bayer Ag | Indolin-Sulfanilsäureamide |
| WO2005056522A2 (en) | 2003-12-04 | 2005-06-23 | National Health Research Institutes | Indole compounds |
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- 2005-10-14 FR FR0510482A patent/FR2890072A1/fr active Pending
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