HRP20191953T1 - DERIVATI 1-BENZIL-3-HIDROKSIMETILINDAZOLA I NJIHOVA UPORABA U LIJEČENJU BOLESTI KOJE SE BAZIRAJU NA EKSPRESIJI MCP-1, CXCR1 i p40 - Google Patents

DERIVATI 1-BENZIL-3-HIDROKSIMETILINDAZOLA I NJIHOVA UPORABA U LIJEČENJU BOLESTI KOJE SE BAZIRAJU NA EKSPRESIJI MCP-1, CXCR1 i p40 Download PDF

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HRP20191953T1
HRP20191953T1 HRP20191953TT HRP20191953T HRP20191953T1 HR P20191953 T1 HRP20191953 T1 HR P20191953T1 HR P20191953T T HRP20191953T T HR P20191953TT HR P20191953 T HRP20191953 T HR P20191953T HR P20191953 T1 HRP20191953 T1 HR P20191953T1
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Angelo Guglielmotti
Guido Furlotti
Giorgina Mangano
Nicola Cazzolla
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Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A.
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Publication of HRP20191953T8 publication Critical patent/HRP20191953T8/hr

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Claims (20)

1. Spoj, naznačen time, da ima sljedeću opću formulu (I): u kojoj: A može biti -X1- ili -X1-O-X2-, gdje X1 i X2 koji mogu biti međusobno isti ili različiti, mogu predstavljati alkil-skupinu s jednim do pet atoma ugljika, te je opcijski supstituirana s jednom ili više alkil-skupina s jednim do pet atoma ugljika ili s jednom ili više alkoksi-skupina s jednim do tri atoma ugljika, gdje Y može predstavljati H, -OH ili N(R11)(R12), dok R11 može predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, ili R11 zajedno s R12 tvori 4-člani do 7-člani heterocikl, R12 može predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, ili R12 zajedno s R11 tvori 4-člani do 7-člani heterocikl, R1 i R2, koji mogu biti međusobno isti ili različiti, mogu predstavljati vodik ili alkil-skupinu s jednim do pet atoma ugljika, R3, R4 i R8, koji mogu biti međusobno isti ili različiti, mogu predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, alkoksi-skupinu s jednim do tri atoma ugljika, atom halogena, -OH, -N(R')(R''), -N(R')COR'', -CN, -CONR'R'', -SO2NR'R'', -SO2R', nitro i trifluorometil, pri čemu su R' i R'', koji mogu biti međusobno isti ili različiti, predstavljeni vodikom i alkil-skupinom s jednim do pet atoma ugljika, R5 može predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, alkoksi-skupinu s jednim do tri atoma ugljika, atom halogena, -OH, -N(R')(R''), -N(R')COR'', nitro i trifluorometil, ili R5 zajedno s jednim od ostataka R6 i R7, tvori prsten koji ima pet ili šest atoma ugljika, gdje su R' i R'', koji mogu biti međusobno isti ili različiti, predstavljeni vodikom i alkil-skupinom s jednim do pet atoma ugljika, R6 i R7, koji mogu biti međusobno isti ili različiti, mogu predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, ili zajedno tvore skupinu C=O, ili jedan od ostataka R6 i R7, zajedno s R5, tvori prsten koji ima pet ili šest atoma ugljika.
2. Spoj prema zahtjevu 1, naznačen time, da su X1 i X2 međusobno neovisno alkil-skupina koja ima od jednoga do četiri atoma ugljika, i koja je opcijski supstituirana s jednom ili više alkil-skupina koje imaju od jednoga do tri atoma ugljika ili s jednom ili više alkoksi-skupina s jednim ili dva atoma ugljika.
3. Spoj prema zahtjevu 1, naznačen time, da X1 je izabran iz skupine koja sadrži CH2-skupinu, CH2CH2-skupinu, C(CH3)2-skupinu, i C(CH3)2CH2-skupinu, a X2 je izabran iz skupine koja obuhvaća sljedeće: CH2-skupinu, CH2CH2-skupinu i CH2CH2CH2-skupinu.
4. Spoj prema zahtjevu 1, naznačen time, da je ostatak A izabran iz skupine koja sadrži CH2CH2-skupinu, CH2CH2CH2-skupinu, C(CH3)2CH2-skupinu, CH2CH2OCH2-skupinu, CH2CH2OCH2CH2-skupinu, i C(CH3)2CH2OCH2-skupinu, te C(CH3)2CH2OCH2CH2-skupinu.
5. Spoj prema zahtjevu 1, naznačen time, da R11 i R12, koji mogu biti međusobno isti ili različiti, predstavljaju atom vodika ili alkil-skupinu s jednim do tri atoma ugljika, ili zajedno tvore 5-člani ili 6-člani heterocikl.
6. Spoj prema zahtjevu 1, naznačen time, da R1 i R2, koji mogu biti međusobno isti ili različiti, predstavljaju atom vodika ili alkil-skupinu s jednim do tri atoma ugljika.
7. Spoj prema zahtjevu 1, naznačen time, da su R3, R4 i R8, koji mogu biti međusobno isti ili različiti, izabrani iz skupine koja sadrži atom vodika, alkil-skupinu s jednim do tri atoma ugljika, alkoksi-skupinu s jednim ili dva atoma ugljika, atome Br, Cl ili F, OH-skupinu, nitro-skupinu, trifluorometil-skupinu ili skupine -N(R')(R''), -N(R')COR'', -CN, -CONR'R'', -SO2NR'R'', -SO2R', s R' i R'', koji mogu biti međusobno isti ili različiti, a predstavljeni su atomom vodika i alkil-skupinom s jednim do tri atoma ugljika.
8. Spoj prema zahtjevu 1, naznačen time, da je R5 izabran iz skupine koja sadrži atom vodika, alkil-skupinu s jednim do tri atoma ugljika, alkoksi-skupinu s jednim ili dva atoma ugljika, atom halogena, OH-skupinu, ili R5 zajedno s jednim od ostataka R6 i R7, tvori prsten koji ima 5 ili 6 atoma ugljika.
9. Spoj prema zahtjevu 1, naznačen time, da su R6 i R7, koji mogu biti međusobno isti ili različiti, izabrani iz skupine koja sadrži atom vodika, alkil-skupinu s jednim do tri atoma ugljika, ili zajedno tvore skupinu C=O, ili jedan od ostataka R6 i R7, zajedno s R5, tvori prsten koji ima 5 ili 6 atoma ugljika.
10. Farmaceutski sastav, naznačen time, da obuhvaća spoj formule (I) prema bilo kojem od prethodnih zahtjeva, ili njegovu farmaceutski prihvatljivu sol ili njegov farmaceutski prihvatljiv ester, te najmanje jedan farmaceutski prihvatljiv nosač.
11. Farmaceutski sastav prema zahtjevu 10, naznačen time, da je navedena farmaceutski prihvatljiva sol takva, da je to adicijska sol s fiziološki prikladnim organskim ili mineralnim kiselinama ili lužinama.
12. Farmaceutski sastav prema zahtjevu 11, naznačen time, da su navedene fiziološki prikladne kiseline izabrane iz skupine koju čine klorovodična kiselina, bromovodična kiselina, sumporna kiselina, fosforna kiselina, dušična kiselina, octena kiselina, askorbinska kiselina, benzojeva kiselina, limunska kiselina, fumarna kiselina, mliječna kiselina, maleična kiselina, metansulfonska kiselina, oksalna kiselina, para-toluensulfonska kiselina, benzensulfonska kiselina, sukcinska kiselina, taninska kiselina i vinska kiselina.
13. Farmaceutski sastav prema zahtjevu 11, naznačen time, da su navedene fiziološki prikladne lužine izabrane iz skupine koju čine amonijev hidroksid, kalcijev hidroksid, magnezijev karbonat, natrij-vodikov karbonat, kalij-vodikov karbonat, arginin, betain, kofein, kolin, N,N-dibenziletilendiamin, dietilamin, 2-dietilaminoetanol, 2-dimetilaminoetanol, etanolamin, etilendiamin, N-etilmorfolin, N-etilpiperidin, N-metilglukamin, glukamin, glukozamin, histidin, N-(2-hidroksietil)piperidin, N-(2-hidroksietil)pirolidin, izopropilamin, lizin, metilglukamin, morfolin, piperazin, piperidin, teobromin, trietilamin, trimetilamin, tripropilamin i trometamin.
14. Farmaceutski sastav prema zahtjevu 10, naznačen time, da se navedeni farmaceutski prihvatljiv ester tvori iz fiziološki prikladnih organskih kiselina koje su izabrane iz skupine koju čine octena kiselina, askorbinska kiselina, benzojeva kiselina, limunska kiselina, fumarna kiselina, mliječna kiselina, maleična kiselina, metansulfonska kiselina, oksalna kiselina, para-toluensulfonska kiselina, benzensulfonska kiselina, sukcinska kiselina, taninska kiselina i vinska kiselina.
15. Farmaceutski sastav prema bilo kojem od zahtjeva 10 do 14, naznačen time, da navedeni sastav sadrži stereoizomer ili enantiomer od spoja formule (I), ili od njegove farmaceutski prihvatljive soli, ili od njegovog farmaceutski prihvatljivog estera, ili od njihove mješavine.
16. Farmaceutski sastav prema bilo kojem od zahtjeva 10 do 15, naznačen time, da je navedeni farmaceutski prihvatljiv nosač izabran iz skupine koju čine klizna sredstva, veziva, dezintegratori, punila, razrjeđivači, pojačivači okusa, bojila, fluidizatori, maziva, konzervansi, ovlaživači, apsorbenti i sladila.
17. Uporaba spoja koji ima sljedeću opću formulu (I): gdje: A može biti -X1- ili -X1-O-X2-, pri čemu X1 i X2 koji mogu biti međusobno isti ili različiti, mogu predstavljati alkil-skupinu s jednim do pet atoma ugljika, te je opcijski supstituirana s jednom ili više alkil-skupina s jednim do pet atoma ugljika ili s jednom ili više alkoksi-skupina s jednim do tri atoma ugljika, gdje Y može predstavljati H, -OH ili N(R11)(R12), dok R11 može predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, ili R11 zajedno s R12 tvori 4-člani do 7-člani heterocikl, R12 može predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, ili R12 zajedno s R11 tvori 4-člani do 7-člani heterocikl, R1 i R2, koji mogu biti međusobno isti ili različiti, mogu predstavljati vodik ili alkil-skupinu s jednim do pet atoma ugljika, R3, R4 i R8, koji mogu biti međusobno isti ili različiti, mogu predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, alkoksi-skupinu s jednim do tri atoma ugljika, atom halogena, -OH, -N(R')(R''), -N(R')COR'', -CN, -CONR'R'', -SO2NR'R'', -SO2R', nitro i trifluorometil, pri čemu su R' i R'', koji mogu biti međusobno isti ili različiti, predstavljeni vodikom i alkil-skupinom s jednim do pet atoma ugljika, R5 može predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, alkoksi-skupinu s jednim do tri atoma ugljika, atom halogena, -OH, -N(R')(R''), -N(R')COR'', nitro i trifluorometil, ili R5 zajedno s jednim od ostataka R6 i R7, tvori prsten koji ima pet ili šest atoma ugljika, gdje su R' i R'', koji mogu biti međusobno isti ili različiti, predstavljeni vodikom i alkil-skupinom s jednim do pet atoma ugljika, R6 i R7, koji mogu biti međusobno isti ili različiti, mogu predstavljati vodik, alkil-skupinu s jednim do pet atoma ugljika, ili zajedno tvore skupinu C=O, ili jedan od ostataka R6 i R7, zajedno s R5, tvori prsten koji ima pet ili šest atoma ugljika, naznačena time, da služi u proizvodnji farmaceutskog sastava za liječenje bolesti koje se baziraju na ekspresiji MCP-1, CX3CR1 i p40, pri čemu su navedene bolesti koje se baziraju na ekspresiji MCP-1 i CX3CR1, izabrane iz skupine koju čine bolesti artikulacije, renalne bolesti, kardiovaskularne bolesti, metabolički sindrom, pretilost, dijabetes, otpornost na inzulin i rak, te time, da su navedene bolesti koje se baziraju na ekspresiji p40 izabrane iz skupine koju čine autoimune bolesti, kronične degenerativne upalne bolesti i rak.
18. Uporaba prema zahtjevu 17, naznačena time, da su navedene bolesti koje se baziraju na ekspresiji MCP-1 izabrane iz skupine koju čine reumatoidni artritis, artritis izazvan virusnim infekcijama, psorijatički artritis, artroza, lupus nefritis, dijabetička nefropatija, glomerulonefritis, bolest policističnih bubrega, intersticijska plućna bolest, fibroza, multipla skleroza, Alzheimerova bolest, demencija povezana s HIV-om, atopijski dermatitis, psorijaza, vaskulitis, restenoza, ateroskleroza, infarkt miokarda, angina, akutne koronarne bolesti, adenomi, karcinomi i metastaze, te metaboličke bolesti.
19. Uporaba prema zahtjevu 17, naznačena time, da su navedene bolesti koje se baziraju na ekspresiji CX3CR1 izabrane iz skupine koju čine reumatoidni artritis, lupus nefritis, dijabetička nefropatija, Crohnova bolest, ulcerativni kolitis, koronarni poremećaji, restenoza, ateroskleroza, infarkt miokarda i angina.
20. Uporaba prema zahtjevu 17, naznačena time, da su navedene bolesti koje se baziraju na ekspresiji p40 izabrane iz skupine koju čine reumatoidni artritis, psorijaza, glomerulonefritis, dijabetes, lupus eritematoza, dijabetes, Crohnova bolest i tumori.
HRP20191953TT 2008-03-07 2019-10-28 DERIVATI 1-BENZIL-3-HIDROKSIMETILINDAZOLA I NJIHOVA UPORABA U LIJEČENJU BOLESTI KOJE SE BAZIRAJU NA EKSPRESIJI MCP-1, CX3CR1 i P40 HRP20191953T8 (hr)

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Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8461194B2 (en) * 2008-03-07 2013-06-11 Aziende Chimiche Riunite Angelini Francesco A. C. R. A. F. S. P. A. 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of MCP-1, CX3CR1 and P40
LT2254869T (lt) * 2008-03-07 2017-08-10 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Nauji 1-benzil-3-hidroksimetilindazolo dariniai ir jų panaudojimas gydyme ligų, susijusių su cx3cr1 ir p40 raiška
AU2009221063B2 (en) 2008-03-07 2013-03-21 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of MCP-1, and CX3CR1
UA108742C2 (uk) 2009-09-23 2015-06-10 Фармацевтична композиція для лікування запальних захворювань, опосередкованих mcp-1
US8435993B2 (en) 2010-12-07 2013-05-07 Philadelphia Health And Education Corporation Methods of inhibiting metastasis from cancer
JP2015521183A (ja) 2012-05-18 2015-07-27 サノフイ ピリジン誘導体および病理学的血栓形成に関連する状態の治療へのその使用
SI2882715T1 (sl) 2012-05-18 2017-03-31 Sanofi Derivati pirazola in njihova uporaba kot antagonisti LPAR5
US9533002B2 (en) * 2012-05-25 2017-01-03 Berg Llc Methods of treating a metabolic syndrome by modulating heat shock protein (HSP) 90-β
IN2014DN10214A (hr) * 2012-06-01 2015-08-07 Nogra Pharma Ltd
US9013997B2 (en) 2012-06-01 2015-04-21 Broadcom Corporation System for performing distributed data cut-through
WO2015188198A2 (en) 2014-06-06 2015-12-10 Berg Llc Methods of treating a metabolic syndrome by modulating heat shock protein (hsp) 90-beta
CA2989270A1 (en) * 2015-06-16 2016-12-22 Translatum Medicus, Inc. Compositions and methods for treating and diagnosing ocular disorders
JP6987746B2 (ja) * 2015-09-28 2022-01-05 ジェネンテック， インコーポレイテッド 治療用化合物及びその使用方法
US11267817B2 (en) 2017-05-02 2022-03-08 Drexel University Substituted pyrrolo[1,2-a]quinoxalin-4(5H)-ones as CX3CR1 antagonists
WO2020261158A1 (en) * 2019-06-25 2020-12-30 Translatum Medicus Inc. Processes of making 2-((1-benzyl-1h-indazol-3-yl)methoxy)-2-methylpropanoic acid and its derivatives

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1230441B (it) 1989-02-07 1991-10-23 Acraf Eteri della serie dell'indazolo
IT1253703B (it) 1991-04-22 1995-08-23 Angelini Francesco Ist Ricerca Uso di acidi metossi alcanoici dell'indazolo per preparare un farmaco attivo nel trattamento di malattie autoimmunitarie
IT1293795B1 (it) 1997-07-28 1999-03-10 Angelini Ricerche Spa Farmaco attivo nel ridurre la produzione di proteina mcp-1
JP2003502424A (ja) 1999-06-17 2003-01-21 シオノギ バイオリサーチ コーポレイション Ｉｌ−１２産生の阻害物質
EP1188438A1 (en) 2000-09-15 2002-03-20 Warner-Lambert Company Pharmaceutical composition for preventing or treating a disease associated with an excess of Il-12 production
EP1199074A1 (en) 2000-09-15 2002-04-24 Warner-Lambert Company Pharmaceutical composition for preventing or treating a disease associated with an excess of il-12 production
EP1369119B1 (en) 2001-03-15 2008-12-17 Seikagaku Corporation Il-12 expression controlling agents
NZ533437A (en) 2001-11-30 2007-05-31 Synta Pharmaceuticals Corp Pyrimidine compounds for treating interleukin-12 (IL12) related diseases
AU2004278276B2 (en) 2003-10-07 2007-10-18 Astrazeneca Ab New 2-substituted, 4-amino-thiazolo(4,5-d) pyrimidines, useful as chemokine receptor antagonists, esp. CX3CR1
US20070015771A1 (en) 2004-07-29 2007-01-18 Threshold Pharmaceuticals, Inc. Lonidamine analogs
US20070043057A1 (en) * 2005-02-09 2007-02-22 Threshold Pharmaceuticals, Inc. Lonidamine analogs
US7514463B2 (en) * 2004-08-20 2009-04-07 University Of Kansas Lonidamine analogues and their use in male contraception and cancer treatment
DE102004043005A1 (de) * 2004-09-02 2006-03-09 Biotronik Vi Patent Ag Signalverarbeitungsvorrichtung für physiologische Signale
US7696202B2 (en) 2004-11-10 2010-04-13 Synta Pharmaceuticals Corp. IL-12 modulatory compounds
JP2006137718A (ja) * 2004-11-12 2006-06-01 Astellas Pharma Inc インドール若しくはインダゾール誘導体
WO2006060194A1 (en) 2004-11-19 2006-06-08 Synta Pharmaceuticals Corp. Pyrimidine compounds and uses thereof
UA90707C2 (en) 2005-04-06 2010-05-25 Астразенека Аб Novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives
AR053347A1 (es) 2005-04-06 2007-05-02 Astrazeneca Ab Derivados de [1,3]tiazolo[4,5-d]pirimidin-2(3h)-ona 5,7-sustituidos
US7858645B2 (en) * 2006-11-01 2010-12-28 Hoffmann-La Roche Inc. Indazole derivatives
CN101074208A (zh) * 2007-06-29 2007-11-21 方炳良 吲哚衍生物的制备方法
LT2254869T (lt) 2008-03-07 2017-08-10 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Nauji 1-benzil-3-hidroksimetilindazolo dariniai ir jų panaudojimas gydyme ligų, susijusių su cx3cr1 ir p40 raiška
AU2009221063B2 (en) * 2008-03-07 2013-03-21 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of MCP-1, and CX3CR1
US8461194B2 (en) * 2008-03-07 2013-06-11 Aziende Chimiche Riunite Angelini Francesco A. C. R. A. F. S. P. A. 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of MCP-1, CX3CR1 and P40
EP2443237B1 (en) * 2009-06-16 2017-02-22 CuRNA, Inc. Treatment of collagen gene related diseases by inhibition of natural antisense transcript to a collagen gene
MX2012001520A (es) * 2009-08-03 2012-06-01 Acraf Proceso para la preparacion de 1-bencil-3-hidroximetil-1h-indazol y sus derivados e intermediarios de magnesio requeridos.
UA108742C2 (uk) 2009-09-23 2015-06-10 Фармацевтична композиція для лікування запальних захворювань, опосередкованих mcp-1

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