HRP20130900T1 - Derivat (aza)indola i njegova uporaba u medicinske svrhe - Google Patents

Derivat (aza)indola i njegova uporaba u medicinske svrhe Download PDF

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HRP20130900T1
HRP20130900T1 HRP20130900AT HRP20130900T HRP20130900T1 HR P20130900 T1 HRP20130900 T1 HR P20130900T1 HR P20130900A T HRP20130900A T HR P20130900AT HR P20130900 T HRP20130900 T HR P20130900T HR P20130900 T1 HRP20130900 T1 HR P20130900T1
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hydroxy
optionally substituted
lower alkyl
cyano
prodrug
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HRP20130900AT
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Kazuo Shimizu
Yasushi Takigawa
Hideki Fujikura
Masato Iizuka
Masahiro Hiratochi
Norihiko Kikuchi
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Kissei Pharmaceutical Co., Ltd.
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Claims (14)

1. Derivat (aza)indola predstavljen općom formulom: [Kem. 1] [image] gdje T predstavlja nitro, cijano ili trifluorometil; prsten J predstavlja prsten benzena; Q predstavlja karboksi ili niži alkoksikarbonil; Y predstavlja hidroksi, amino, atom halogena, nitro, po izboru supstituirani niži alkil ili po izboru supstituirani niži alkoksi uz uvjet da dva ili više Y po izboru postoje na prstenu J i ti Y su po izboru isti ili međusobno različiti; X1, X2 i X3 nezavisno predstavljaju CR2 ili N uz uvjet da svi od X1, X2 i X3 ne predstavljaju N u isto vrijeme, i kada dva ili više R2 postoje, ti R2 su po izboru isti ili međusobno različiti; i R1 i R2 nezavisno predstavljaju atom halogena, cijano, perfluoro (niži alkil) , -AA, -A- D- E- G ili - N (- D- EG)2 uz uvjet da su dva (- D- E- G) po izboru međusobno različiti; u formuli, AA predstavlja atom vodika, hidroksi, tiol, -CHO, karboksi, -CONHR3, -NHR3, -N(R3) CHO, -N(R3) CONHR4 ili - SO2NHR3; A predstavlja jednostruku vezu, -O-, -S-, -CO-, -COO-, -CON (R3)-, -SO2-, -SO2N (R3)-, -N (R3)-, -N (R3) CO-, -N (R3)COO-, -N (R3) SO2- ili - N (R3) CONR4- gdje R3 i R4 nezavisno predstavljaju atom vodika ili niži alkil; D predstavlja po izboru supstituirani niži alkilen, po izboru supstituirani niži alkenilen, po izboru supstituirani niži alkinilen, po izboru supstituirani cikloalkilen, po izboru supstituirani heterocikloalkilnen, po izboru supstituirani arilen ili po izboru supstituirani heteroarilen uz uvjet da je D is po izboru dalje supstituiran s - E- G; E predstavlja jednostruku vezu, -O-, -N (R5)-, -S-, -CO-, -COO-, -CON (R5)-, -SO2-, -SO2N (R5)-, -N (R5) CO-, -N (R5)COO-, -N (R5) SO2- ili - N (R5) CON (R6)- uz uvjet da R5 i R6 nezavisno predstavljaju atom vodika ili niži alkil; i G predstavlja atom vodika, po izboru supstituirani niži alkil, po izboru supstituirani niži alkenil, po izboru supstituirani niži alkinil, po izboru supstituirani cikloalkil, po izboru supstituirani heterocikloalkil, po izboru supstituirani aril, po izboru supstituirani heteroaril, po izboru supstituirani cikloalkil (niži alkil), po izboru supstituirani heterocikloalkil (niži alkil), po izboru supstituirani aril (niži alkil) ili po izboru supstituirani heteroaril (niži alkil) uz uvjet da kada je G atom vodika, E je jednostruka veza, -O-, -N (R5)-, -S-, -COO-, -CON(R5)-, -N(R5)CO-, -N(R5)CON(R6)- ili -SO2N(R5)-, ili R5 i R6 se po izboru vežu zajedno da formiraju prsten, ili uz uvjet da kada postoji veza R1 i R2 ili dva R2 za susjedne atome, ti R1 i R2, odnosno ili dva R2 se po izboru vežu zajedno da formiraju prsten; ili njegov prolijek, ili farmaceutski prihvatljiva sol; pri čemu "niži" znači ravnolančani ili razgranati ugljikovodik sa 6 ili manje atoma ugljika; i "prolijek" je spoj gdje je bilo koja ili više skupina izabranih između hidroksi, amino i karboksi u spoju predstavljenom gornjom općom formulom (I) zamijenjena skupinom koja daje prolijek, gdje se skupina koja daje prolijek izabire iz grupa koja obuhvaća: u hidroksi ili amino skupini, (niži alkil)-CO-, aril-CO-, (niži alkil)-O-(niži alkilen)-CO, (niži alkil)-OCO-(niži alkilen)-CO-, (niži alkil)-OCO-, (niži alkil)-O-(niži alkilen)-OCO-, (niži alkil)-COO-(niži alkilen), (niži alkil)-OCOO-(niži alkilen), cikloalkil-OCOO-(niži alkilen) i ester ili amid s aminokiselinom; u karboksi skupini, niži alkil, (niži alkil)-COO-(niži alkilen), (niži alkil)-OCOO-(niži alkilen) i cikloalkil-OCOO-(niži alkilen).
2. Derivat (aza)indola prema zahtjevu 1, gdje X1, X2 i X3 nezavisno predstavljaju CR2 uz uvjet da kada dva ili više R2 postoje, ti R2 su po izboru isti ili međusobno različiti, ili njegov prolijek, ili farmaceutski prihvatljiva sol.
3. Derivat (aza)indola prema zahtjevu 1 ili 2, gdje T predstavlja cijano, ili njegov prolijek, ili farmaceutski prihvatljiva sol.
4. Derivat (aza)indola prema bilo kojem od zahtjeva 1 do 3, gdje Q predstavlja karboksi, ili njegov prolijek, ili farmaceutski prihvatljiva sol.
5. Derivat (aza)indola prema bilo kojem od zahtjeva 1 do 4, gdje Y predstavlja hidroksi ili atom halogena, ili njegov prolijek, ili farmaceutski prihvatljiva sol, ili gdje Y predstavlja hidroksi, ili njegov prolijek, ili farmaceutski prihvatljiva sol.
6. Derivat (aza)indola prema zahtjevu 4, gdje skupina predstavljena općom formulom: [Kem. 2] [image] jest skupina predstavljena sljedećom općom formulom (IIa): [Kem. 3] [image] u formuli, Z1, Z2 i Z3 nezavisno predstavljaju CR7; i Y1 predstavlja hidroksi, amino, atom halogena, niži alkil ili niži alkoksi; i R7 predstavlja atom vodika, hidroksi, amino, atom halogena, niži alkil ili niži alkoksi uz uvjet da kada dva ili više R7 postoje, ti R7 su po izboru isti ili međusobno različiti, ili njegov prolijek, ili farmaceutski prihvatljiva sol, ili gdje Z1 i Z3 predstavljaju CH, i Z2 predstavlja CR8; i Y1 predstavlja hidroksi ili atom halogena; i R8 predstavlja atom vodika, hidroksi ili atom halogena, ili njegov prolijek, ili farmaceutski prihvatljiva sol.
7. Derivat (aza)indola prema bilo kojem od zahtjeva 1 do 5, koji je predstavljen sljedećom općom formulom (IA) [Kem. 9] [image] u formuli, R1 ima isto značenje kako je definirano u zahtjevu 1, ili njegov prolijek, ili farmaceutski prihvatljiva sol.
8. Derivat (aza)indola prema zahtjevu 7, koji se izabire iz grupe koja obuhvaća: 4-(3-cijano-5,6-difluoro-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-indol-1-il)-2-hidroksi- benzojeva kiselina, 4-(3-cijano-5-metil-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-6-chloro-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-5-fluoro-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-6-fluoro-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(6-klor-3-cijano-5-fluoro- indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(7-cijano-1,3-dioksolo[4,5-f]indol-5-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-5-metoksi-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-5-hidroksi-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-4-fluoro-indol-1-il)-2-hidroksi-benzojeva kiselina, 4-(3-cijano-6-izopropil-indol-1-il)-2-hidroksi-benzojeva kiselina, i i njegova farmaceutski prihvatljiva sol.
9. Inhibitor ksantin oksidaze koji kao djelatnu tvar sadrži derivat (aza)indola ili njegov prolijek, ili farmaceutski prihvatljivu sol prema bilo kojem od zahtjeva 1 do 8.
10. Farmaceutska smjesa koja kao djelatnu tvar sadrži derivat (aza)indola ili njegov prolijek, ili farmaceutski prihvatljivu sol prema bilo kojem od zahtjeva 1 do 8.
11. Farmaceutska smjesa prema zahtjevu 10 za uporabu u prevenciji ili liječenju bolesti izabrane iz grupe koja obuhvaća hiperurikemiju, giht s kamencima, artritični giht, poremećaj bubrega povezan s hiperurikemijom i urinarne kamence.
12. Farmaceutska smjesa prema zahtjevu 11 za uporabu u prevenciji ili liječenju hiperurikemije.
13. Farmaceutska smjesa prema zahtjevu 10 za uporabu u snižavanju razine urične kiseline u serumu, ili inhibiciji proizvodnje urične kiseline.
14. Farmaceutska smjesa prema bilo kojem od zahtjeva 10 do 13, koja sadrži daljnju kombinaciju s najmanje jednim lijekom izabranim iz grupe koja obuhvaća kolhicine, nesteroidni protuupalni lijek, steroid i sredstvo za alkalizaciju urna kao djelatnu tvar.
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Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20080066938A (ko) 2005-10-07 2008-07-17 깃세이 야쿠힌 고교 가부시키가이샤 질소 함유 복소환 화합물 및 그것을 함유하는 의약 조성물
CN101679251B (zh) * 2007-04-11 2013-10-02 橘生药品工业株式会社 (氮杂)吲哚衍生物及其医药用途
WO2010093191A2 (en) * 2009-02-13 2010-08-19 Lg Life Sciences Ltd. Novel compounds effective as xanthine oxidase inhibitors, method for preparing the same, and pharmaceutical composition containing the same
JP5638513B2 (ja) * 2009-03-31 2014-12-10 キッセイ薬品工業株式会社 インドリジン誘導体及びその医薬用途
KR101256018B1 (ko) 2009-08-20 2013-04-18 한국과학기술연구원 단백질 키나아제 저해활성을 갖는 1,3,6-치환된 인돌 화합물
TWI423962B (zh) 2009-10-07 2014-01-21 Lg Life Sciences Ltd 有效作為黃嘌呤氧化酶抑制劑之新穎化合物、其製備方法及含該化合物之醫藥組成物
AR081930A1 (es) * 2010-06-16 2012-10-31 Ardea Biosciences Inc Compuestos de tioacetato
EP2623505B1 (en) * 2010-09-29 2015-07-29 Kissei Pharmaceutical Co., Ltd. (aza)indolizine derivatives as xanthine oxidase inhibitors
DK2669270T3 (en) 2011-01-28 2018-02-26 Sato Pharma Indole-related compounds such as URAT1 inhibitors
TWI548630B (zh) * 2011-04-06 2016-09-11 Ｌｇ生命科學有限公司 １－（３－氰基－１－異丙基－吲哚－５－基）吡唑－４－羧酸結晶型及其製造方法
WO2013027801A1 (ja) 2011-08-24 2013-02-28 キッセイ薬品工業株式会社 縮合へテロ環誘導体及びその医薬用途
WO2013061962A1 (ja) 2011-10-24 2013-05-02 武田薬品工業株式会社 二環性化合物
EP2878594B1 (en) * 2012-07-27 2018-11-28 Sato Pharmaceutical Co., Ltd. Difluoromethylene compound
CN103980267B (zh) * 2013-02-08 2018-02-06 镇江新元素医药科技有限公司 一类新型黄嘌呤氧化酶抑制剂的化合物及其药物组合物
WO2014132994A1 (ja) * 2013-02-27 2014-09-04 キッセイ薬品工業株式会社 含窒素複素環誘導体の製造方法およびその製造中間体
WO2015025914A1 (ja) * 2013-08-22 2015-02-26 キッセイ薬品工業株式会社 インドール誘導体の塩及びその結晶
JP6823359B2 (ja) * 2014-06-09 2021-02-03 キッセイ薬品工業株式会社 インドール誘導体の塩及びその結晶
AU2016316278B2 (en) 2015-09-02 2020-06-04 Sunshine Lake Pharma Co., Ltd. Carboxy substituted (hetero) aromatic ring derivatives and preparation method and uses thereof
CN106008488B (zh) * 2016-05-20 2018-10-30 广东东阳光药业有限公司 氰基吲哚类衍生物及其制备方法和用途
WO2017202291A1 (zh) * 2016-05-23 2017-11-30 南京明德新药研发股份有限公司 噻吩化合物及其合成方法和其在医药上的应用
CN106045898B (zh) * 2016-06-28 2019-05-24 广东东阳光药业有限公司 一种吲哚类化合物及其制备方法和用途
WO2018013430A2 (en) 2016-07-12 2018-01-18 Arisan Therapeutics Inc. Heterocyclic compounds for the treatment of arenavirus infection
CN107501162B (zh) * 2017-07-07 2021-06-25 浙江工业大学 一种n-酰基取代的吲哚衍生物的制备方法
CN107987006B (zh) * 2017-12-20 2021-06-01 华润赛科药业有限责任公司 吲哚类或氮杂吲哚类衍生物、其制备方法和应用
CN111943957B (zh) * 2019-05-17 2023-01-06 中国医学科学院药物研究所 喹啉甲酰胺类化合物及其制备方法和用途
CN114555578B (zh) * 2019-10-30 2024-03-26 东宝紫星(杭州)生物医药有限公司 作为黄嘌呤氧化酶抑制剂的噻吩衍生物及其应用
CN111072634B (zh) * 2020-01-03 2022-07-22 中国医科大学 1-取代-3-取代-5-取代酰胺-1h-吲哚类化合物及其制备方法和应用
IL301768A (en) * 2020-09-30 2023-05-01 Fl2022 001 Inc HSD17B13 inhibitors and uses thereof
US20240000750A1 (en) * 2020-11-04 2024-01-04 Lg Chem, Ltd. Method for preparing crystalline particles of 1-(3-cyano-1-isopropyl-indole-5-yl)pyrazole-4-carboxylic acid, and pharmaceutical composition comprising same
JP2023551524A (ja) * 2020-12-01 2023-12-08 エルジー・ケム・リミテッド １－（３－シアノ－１－イソプロピル－インドール－５－イル）ピラゾール－４－カルボン酸を含む経口用製剤、およびその製造方法
KR20220077091A (ko) * 2020-12-01 2022-06-08 주식회사 엘지화학 1-(3-시아노-1-아이소프로필-인돌-5-일)피라졸-4-카르복실산을 포함하는 안정한 경구용 제제
JP2024511899A (ja) * 2021-04-16 2024-03-15 エルジー・ケム・リミテッド １－（３－シアノ－１－イソプロピル－インドール－５－イル）ピラゾール－４－カルボン酸を含む経口用製剤
KR20220147529A (ko) * 2021-04-27 2022-11-03 주식회사 엘지화학 잔틴 옥시다아제 저해제 합성을 위한 중간체의 제조 방법
WO2022231262A1 (ko) * 2021-04-27 2022-11-03 주식회사 엘지화학 잔틴 옥시다아제 저해제의 제조 방법
AU2022294728A1 (en) * 2021-06-15 2024-01-04 Lg Chem, Ltd. Pharmaceutical composition comprising 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid
AR126164A1 (es) * 2021-06-17 2023-09-27 Lg Chemical Ltd Formulación compuesta para dosificación oral que comprende ácido 1-(3-ciano-1-isopropil-indol-5-il)pirazol-4-carboxílico
TWI822151B (zh) * 2021-07-02 2023-11-11 南韓商Ｌｇ化學股份有限公司 製備黃嘌呤氧化酶抑制劑的方法

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3370063A (en) * 1964-10-05 1968-02-20 Mcneilab Inc Substituted dimethoxy indoles and method of making the same
AU692484B2 (en) * 1993-10-12 1998-06-11 Du Pont Pharmaceuticals Company 1N-alkyl-N-arylpyrimidinamines and derivatives thereof
US5696143A (en) * 1994-09-20 1997-12-09 Talley; John J. Benz G! indazolyl derivatives for the treatment of inflammation
ID21775A (id) 1996-10-25 1999-07-22 Yoshitomi Pharmaceutical Senyawa-senyawa 1-fenilpirazol dan penggunaan farmasinya
JP2000001431A (ja) * 1998-06-15 2000-01-07 Kotobuki Seiyaku Kk 尿酸排泄剤
US6573262B2 (en) 2000-07-10 2003-06-03 Bristol-Myers Sqibb Company Composition and antiviral activity of substituted indoleoxoacetic piperazine derivatives
ES2250422T3 (es) 2000-07-10 2006-04-16 Bristol-Myers Squibb Company Composicion y actividad antiviral de derivados de piperazina indoloxoaceticos sustituidos.
DE10053275A1 (de) * 2000-10-27 2002-05-02 Dresden Arzneimittel Neue 7-Azaindole, deren Verwendung als Inhibitoren der Phosphodiesterase 4 und Verfahren zu deren Herstellung
SE0301372D0 (sv) 2003-05-09 2003-05-09 Astrazeneca Ab Novel compounds
SE0302232D0 (sv) 2003-08-18 2003-08-18 Astrazeneca Ab Novel Compounds
JP4951517B2 (ja) 2005-09-30 2012-06-13 三菱伸銅株式会社 溶融固化処理物並びに溶融固化処理用銅合金材及びその製造方法
KR20080066938A (ko) * 2005-10-07 2008-07-17 깃세이 야쿠힌 고교 가부시키가이샤 질소 함유 복소환 화합물 및 그것을 함유하는 의약 조성물
CN101679251B (zh) * 2007-04-11 2013-10-02 橘生药品工业株式会社 (氮杂)吲哚衍生物及其医药用途

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