FIELD: medicine; pharmaceuticals.
SUBSTANCE: invention relates to a novel compound—1-((3S,4R)-4-(3-fluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(4-methyl-3-(2-methylpyrimidin-5-yl)-1-phenyl-1H-pyrazol-5-yl)urea of formula I or its dihydrochloride salt. Compounds have the properties of a selective TrkA kinase inhibitor and can be used to treat a disease or disorders selected from a group consisting of pain, cancer, inflammation or inflammatory diseases, endometriosis, diabetic peripheral neuropathy, prostatitis, pelvic pain syndrome, diseases associated with bone tissue remodeling imbalance, as well as diseases caused by aberrant transmission of connective tissue growth factor signals. Novel compound corresponds to formula I
![](/patent/RU2719489C2/i/00000084.png)
and can be obtained by reacting a compound of formula II-A with compound III, or IV, or VII
with removal of protective groups, in case of their presence, and optionally obtaining a dihydrochloride salt of compound I. Either the compound of formula I can be obtained by reacting compound V or VI
![](/patent/RU2719489C2/i/00000089.png)
with compound III, and removing protective groups, if any, and optionally obtaining the dihydrochloride salt of compound I. Reaction conditions and values of radicals are given in the claim.
EFFECT: compound of formula I and its dihydrochloride salt have considerably higher activity indices when used in comparison with closest analogues and are intended for oral administration.
27 cl, 4 dwg, 13 tbl, 9 ex
Title |
Year |
Author |
Number |
N-PYRROLIDINYL-UREA, N'-PYRAZOLYL-UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS |
2013 |
- Allen Shelli
- Brandkhuber Barbara Dzh.
- Kerkher Timoti
- Kolakovski Gabriel R.
- Vinski Shennon L.
|
RU2677667C2 |
LIQUID COMPOSITIONS (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDINE-1-YL)PYRAZOLO[1,5-A]PYRIMIDINE-3-YL)-3-HYDROXYPYRROLIDINE-1-ARBOXAMIDE |
2017 |
- Rejnolds Mark
- Smit Stiven A.
|
RU2751767C2 |
PYRROLIDINYL UREA AND PYRROLIDINYL THIOUREA COMPOUNDS AS TRKA KINASE INHIBITORS |
2012 |
- Allen Shelli
- Endryus Stiven U.
- Blejk Dzhejms F.
- Kondroski Kevin R.
- Khaas Yuliya
- Khuan Lili
- Tszyan Yujtun
- Kerkher Timoti
- Kolakovski Gabriel R.
- Seo Dzeongbeob
|
RU2606131C2 |
CRYSTALLINE FORM (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)-PYRROLIDIN-1-YL)-PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE HYDROSULPHATE |
2015 |
- Errigo Alisha B.
- Dzhuengst Derrik
- Shakh Khalid
|
RU2723990C2 |
CRYSTALLINE (2S,4R)-5-(5'-CHLOR-2'-FLUORO-[1,1'-BIPHENYL]-4-YL)-2-(ETHOXYMETHYL)-4-(3-HYDROXYISOXAZOL-5-CARBOXAMIDO)-2-METHYLPENTANIC ACID AND ITS APPLICATIONS |
2017 |
- Hughes, Adam D.
- Fleury, Melissa
- Rapta, Miroslav
- Thalladi, Venkat R.
- Fass, Gene Timothy
- Simeone, Michael
- Baldwin, R. Michael
- Bourdet, David L.
|
RU2756223C2 |
SUBSTITUTED COMPOUNDS OF PYRAZOLE[1,5-a]PYRIMIDINE AS TRK KINASE INHIBITORS |
2010 |
- Allen Shelli
- Endrjus Stiven S.
- Kondroski Kevin Ronald
- Khaas Julija
- Khuan Lili
- Tszjan Jujtun
- Kerkher Timoti
- Seo Dzeongbeob
|
RU2584157C2 |
DOUBLE NEUROKININ-1/NEUROKININ-3 RECEPTOR ANTAGONISTS FOR TREATING SEX HORMONE DEPENDENT DISEASES |
2016 |
|
RU2743206C2 |
[4-(5-AMINOMETHYL-2-FLOUROPHENYL)-PYPERIDIN-1-YL]-(7- FLUORO-1-(2-METHOXYETHYL)-4-TRIFLUOROMETHOXY-1H-INDOL-3-YL]-METHANONE AS MAST CELL TRYPTASE INHIBITOR |
2009 |
- Choi-Sledeski Jong Mi
- Choj Nakien
- Poli Gregori Bernard
- Shej Dzhon Dzh. Ml.
- Shum Patrik Vai-Kvok
- Sledeski Adam V.
|
RU2509766C2 |
COMBINATION CONTAINING PALBOCICLIB AND 6-(2,4-DICHLOROPHENYL)-5-[4-[(3S)-1-(3-FLUOROPROPYL)PYRROLIDINE-3-YL]-8,9-DIHYDRO-7H-BENZO[7]ANNULENE-2-CARBOXYLIC ACID AND APPLICATION THEREOF FOR TREATING CANCER |
2018 |
- Bouaboula, Monsif
- Shomali, Maysoun
- Sun, Fangxian
|
RU2764116C2 |
SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TROPOMYOSIN-RELATED KINASE INHIBITORS |
2009 |
- Khaas Julija
- Ehndrjus Stiven U.
- Tszjan Jujtun
- Chzhan Gan'
|
RU2523544C2 |