BR112013014242B1 - Composição farmacêutica e composto ou seu sal farmaceuticamente aceitável - Google Patents
Composição farmacêutica e composto ou seu sal farmaceuticamente aceitável Download PDFInfo
- Publication number
- BR112013014242B1 BR112013014242B1 BR112013014242-1A BR112013014242A BR112013014242B1 BR 112013014242 B1 BR112013014242 B1 BR 112013014242B1 BR 112013014242 A BR112013014242 A BR 112013014242A BR 112013014242 B1 BR112013014242 B1 BR 112013014242B1
- Authority
- BR
- Brazil
- Prior art keywords
- carboxamide
- pyrimidine
- dihydropyrazole
- difluoromethyl
- methyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 105
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 26
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- -1 cyano, nitro, amino Chemical group 0.000 claims description 64
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42094610P | 2010-12-08 | 2010-12-08 | |
| US61/420,946 | 2010-12-08 | ||
| PCT/US2011/063928 WO2012078855A1 (en) | 2010-12-08 | 2011-12-08 | Substituted pyrazolopyrimidines as glucocerebrosidase activators |
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| BR112013014242A2 BR112013014242A2 (pt) | 2018-06-26 |
| BR112013014242B1 true BR112013014242B1 (pt) | 2022-02-22 |
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| BR112013014242-1A BR112013014242B1 (pt) | 2010-12-08 | 2011-12-08 | Composição farmacêutica e composto ou seu sal farmaceuticamente aceitável |
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| EP (2) | EP3366688B1 (https=) |
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| CN (1) | CN103534255B (https=) |
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| BR (1) | BR112013014242B1 (https=) |
| CA (1) | CA2820362C (https=) |
| CY (1) | CY1125186T1 (https=) |
| DK (2) | DK2649075T3 (https=) |
| ES (2) | ES2681218T3 (https=) |
| HR (1) | HRP20220512T1 (https=) |
| HU (1) | HUE038635T2 (https=) |
| IL (2) | IL226767B (https=) |
| LT (1) | LT3366688T (https=) |
| MX (2) | MX354506B (https=) |
| PL (2) | PL3366688T3 (https=) |
| PT (2) | PT3366688T (https=) |
| RS (1) | RS63320B1 (https=) |
| RU (1) | RU2603637C2 (https=) |
| SI (2) | SI3366688T1 (https=) |
| TR (1) | TR201810523T4 (https=) |
| WO (1) | WO2012078855A1 (https=) |
| ZA (1) | ZA201304215B (https=) |
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| DK2649075T3 (en) | 2010-12-08 | 2018-07-30 | Us Health | SUBSTITUTED PYRAZOLOPYRIMIDINES AS GLUCOCEREBROSIDASE ACTIVATORS |
| WO2012178125A1 (en) | 2011-06-22 | 2012-12-27 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2012177997A1 (en) | 2011-06-22 | 2012-12-27 | The General Hospital Corporation | Treatment of proteinopathies |
| US8710043B2 (en) | 2011-06-24 | 2014-04-29 | Amgen Inc. | TRPM8 antagonists and their use in treatments |
| EP2723718A1 (en) | 2011-06-24 | 2014-04-30 | Amgen Inc. | Trpm8 antagonists and their use in treatments |
| RU2014120166A (ru) | 2011-10-20 | 2015-11-27 | ГЛЭКСОСМИТКЛАЙН ЭлЭлСи | Замещенные бициклические аза-гетероциклы и их аналоги в качестве модуляторов сиртуина |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US8952009B2 (en) | 2012-08-06 | 2015-02-10 | Amgen Inc. | Chroman derivatives as TRPM8 inhibitors |
| SI2941432T1 (en) | 2012-12-07 | 2018-07-31 | Vertex Pharmaceuticals Incorporated | 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR |
| WO2014143242A1 (en) | 2013-03-15 | 2014-09-18 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| EP2970289A1 (en) | 2013-03-15 | 2016-01-20 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| JP2016512815A (ja) | 2013-03-15 | 2016-05-09 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体 |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| MX2021012208A (es) | 2013-10-04 | 2023-01-19 | Infinity Pharmaceuticals Inc | Compuestos heterocíclicos y usos de los mismos. |
| DK3077397T3 (da) | 2013-12-06 | 2019-12-16 | Vertex Pharma | 2-amino-6-fluor-n-[5-fluor-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamidforbindelse anvendelig som atr-kinase-inhibitor, dens fremstilling, forskellige faste former og radiomarkerede derivater deraf |
| NZ724368A (en) | 2014-03-19 | 2023-07-28 | Infinity Pharmaceuticals Inc | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
| PL3152212T3 (pl) | 2014-06-05 | 2020-06-15 | Vertex Pharmaceuticals Inc. | Radioznakowane pochodne związku 2-amino-6-fluoro-n-[5-fluoro-piridyn-3-ylo]-pirazolo[1,5-a]pirymidino-3-karboksamidu przydatne jako inhibitor kinazy atr, wytwarzanie tego związku i jego różnych postaci stałych |
| LT3157566T (lt) | 2014-06-17 | 2019-08-12 | Vertex Pharmaceuticals Incorporated | Vėžio gydymo būdas, panaudojant chk1 ir atr inhibitorių derinį |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| PE20170920A1 (es) | 2014-11-03 | 2017-07-12 | Bayer Pharma AG | Piperidinilpirazolopirimidinonas y utilizacion de las mismas |
| WO2016073889A1 (en) | 2014-11-06 | 2016-05-12 | Lysosomal Therapeutics Inc. | Substituted imidazo[1,5-a]pyrimidines and their use in the treatment of medical disorders |
| AU2015342883B2 (en) | 2014-11-06 | 2020-07-02 | Bial - R&D Investments, S.A. | Substituted pyrrolo(1,2-a)pyrimidines and their use in the treatment of medical disorders |
| HRP20240644T1 (hr) * | 2014-11-06 | 2024-08-02 | Bial-R&D Investments, S.A. | Supstituirani pirazolo(1,5-a)pirimidini i njihova uporaba u liječenju medicinskih poremećaja |
| CN108290894A (zh) * | 2015-07-01 | 2018-07-17 | 西北大学 | 被取代的4-甲基-吡咯并[1,2-a]嘧啶-8-甲酰胺类化合物及其调节葡糖脑苷脂酶活性的用途 |
| WO2017040879A1 (en) * | 2015-09-04 | 2017-03-09 | Lysosomal Therapeutics Inc. | Thiazolo(3,2-a) pyrimidinone and other heterobicyclic pyrimidinone compounds for use in medical therapy |
| WO2017040877A1 (en) * | 2015-09-04 | 2017-03-09 | Lysosomal Therapeutics Inc. | Heterobicyclic pyrimidinone compounds and their use in the treatment of medical disorders |
| EP4585268A3 (en) | 2015-09-14 | 2025-10-15 | Twelve Therapeutics, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| HK1258570A1 (zh) | 2015-09-30 | 2019-11-15 | Vertex Pharmaceuticals Inc. | 使用dna损伤剂及atr抑制剂的组合治疗癌症的方法 |
| WO2017161137A1 (en) * | 2016-03-16 | 2017-09-21 | Lysosomal Therapeutics Inc. | Methods and compositions for treating a neurodegenerative disorder in a sphingotyped subject |
| US10759806B2 (en) | 2016-03-17 | 2020-09-01 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as PI3K kinase inhibitors |
| US11192892B2 (en) * | 2016-04-06 | 2021-12-07 | Bial—R&D Investments, S.A. | Substituted pyrazolo[1,5-a]pyrimidines for the treatment of medical disorders |
| CA3020305A1 (en) | 2016-04-06 | 2017-10-12 | Lysosomal Therapeutics Inc. | Imidazo [1,5-a]pyrimidinyl carboxamide compounds and their use in the treatment of medical disorders |
| EP3440081A4 (en) * | 2016-04-06 | 2019-09-18 | Lysosomal Therapeutics Inc. | PYRROLO [1,2-A] PYRIMIDINYL-CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDER |
| EP3452455A4 (en) * | 2016-05-05 | 2019-11-13 | Lysosomal Therapeutics Inc. | SUBSTITUTED IMDAZO [1,2-] PYRIDINES, SUBSTITUTED IMIDAZO [1,2-] PYRAZINES, RELATED COMPOUNDS AND THEIR USE IN THE TREATMENT OF ILLNESSES |
| WO2017192929A1 (en) * | 2016-05-05 | 2017-11-09 | Lysosomal Therapeutics Inc. | SUBSTITUTED PYRROLO[1,2-α]TRIAZINES AND RELATED COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS |
| SG11201809693SA (en) * | 2016-05-05 | 2018-11-29 | Lysosomal Therapeutics Inc | SUBSTITUTED IMIDAZO[1,2-b]PYRIDAZINES, SUBSTITUTED IMIDAZO[1,5-b]PYRIDAZINES, RELATED COMPOUNDS, AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN109890829B (zh) * | 2016-11-02 | 2022-07-15 | 豪夫迈·罗氏有限公司 | 作为IRAK4调节剂的吡唑并[1,5a]嘧啶衍生物 |
| KR102717819B1 (ko) * | 2017-07-28 | 2024-10-14 | 다케다 야쿠힌 고교 가부시키가이샤 | Tyk2 억제제 및 이의 용도 |
| US12291533B2 (en) | 2017-08-02 | 2025-05-06 | Northwestern University | Substituted fused pyrimidine compounds and uses thereof |
| BR112020003725A2 (pt) | 2017-10-06 | 2020-11-03 | Forma Therapeutics, Inc. | inibição da peptidase 30 específica de ubiquitina |
| US11459325B2 (en) | 2018-01-31 | 2022-10-04 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス，インコーポレイテッド | ユビキチン特異的ペプチダーゼ３０（ｕｓｐ３０）阻害剤として有用な縮合二環化合物 |
| US10882865B2 (en) | 2018-08-31 | 2021-01-05 | Northwestern University | Pyrrolopyrimidine compounds and uses thereof for modulating glucocerebrosidase activity |
| JP7179161B2 (ja) | 2018-09-10 | 2022-11-28 | イーライ リリー アンド カンパニー | 乾癬および全身性エリテマトーデスの処置に有用なピラゾロ［１，５－ａ］ピリミジン－３－カルボキサミド誘導体 |
| LT3860989T (lt) | 2018-10-05 | 2023-06-12 | Forma Therapeutics, Inc. | Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai |
| JP7619951B2 (ja) * | 2018-10-15 | 2025-01-22 | 武田薬品工業株式会社 | Ｔｙｋ２阻害剤およびその使用 |
| TWI800696B (zh) | 2018-12-10 | 2023-05-01 | 美商美國禮來大藥廠 | 7-(甲基胺基)吡唑并[1,5-a]嘧啶-3-甲醯胺衍生物 |
| ES3055173T3 (en) * | 2019-08-21 | 2026-02-10 | Scripps Research Inst | Bicyclic agonists of stimulator of interferon genes sting |
| KR20220100858A (ko) | 2019-09-17 | 2022-07-18 | 비알 - 알&디 인베스트먼츠, 에스.에이. | 치환된 이미다졸 카르복사미드, 및 질병의 치료에서의 이의 용도 |
| KR20220100860A (ko) | 2019-09-17 | 2022-07-18 | 비알 - 알&디 인베스트먼츠, 에스.에이. | 질병의 치료에 사용하기 위한 치환된, 포화 및 불포화 n-헤테로시클릭 카르복사미드 및 관련 화합물 |
| JP2022548747A (ja) | 2019-09-17 | 2022-11-21 | バイアル－アールアンドディー インベストメンツ ソシエダッド アノニマ | 酸性セラミダーゼ阻害剤としての置換されたｎ－複素環式カルボキサミド及び医薬としてのその使用 |
| BR112022010127A2 (pt) * | 2019-11-25 | 2022-09-06 | Gain Therapeutics Sa | Compostos de arila e heteroarila e usos terapêuticos dos mesmos em condições associadas à alteração da atividade de galatocerebrosidase |
| TWI810520B (zh) | 2020-02-12 | 2023-08-01 | 美商美國禮來大藥廠 | 7-(甲基胺基)吡唑并[1,5-a]嘧啶-3-甲醯胺化合物 |
| WO2021162944A1 (en) | 2020-02-12 | 2021-08-19 | Eli Lilly And Company | Substituted 7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide derivatives |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004037373A2 (en) | 2002-10-21 | 2004-05-06 | The Scripps Research Institute | CHEMICAL CHAPERONES AND THEIR EFFECT UPON THE CELLULAR ACTIVITY OF β-GLUCOSIDASE |
| JP2004277337A (ja) | 2003-03-14 | 2004-10-07 | Sumitomo Pharmaceut Co Ltd | ピラゾロ［１，５−ａ］ピリミジン誘導体 |
| WO2004089471A2 (en) * | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | NEW PYRAZOLO[1,5-a] PYRIMIDINES DERIVATIVES AND PHARMACEUTICAL USE THEREOF |
| EP1682504B1 (en) | 2003-11-12 | 2012-12-26 | Amicus Therapeutics Inc. | Hydroxy piperidine derivatives to treat gaucher disease |
| US7488721B2 (en) | 2004-05-13 | 2009-02-10 | Mcmaster University | Real time methylumbelliferone-based assay |
| NZ551424A (en) | 2004-05-14 | 2009-10-30 | Childrenaes Cancer Inst Austra | Small molecule inhibitors for MRP1 and other multidrug transporters |
| HRP20080070T3 (en) * | 2004-06-21 | 2008-05-31 | F. Hoffmann - La Roche Ag | Pyrrazolo-pyrimidine derivatives |
| DE102005007534A1 (de) | 2005-02-17 | 2006-08-31 | Bayer Cropscience Ag | Pyrazolopyrimidine |
| CA2608890C (en) | 2005-05-20 | 2011-08-02 | Alantos-Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
| US20070155737A1 (en) | 2005-05-20 | 2007-07-05 | Alantos Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
| WO2007008541A2 (en) | 2005-07-08 | 2007-01-18 | Kalypsys, Inc. | Cellular cholesterol absorption modifiers |
| CN102659774A (zh) * | 2005-08-15 | 2012-09-12 | 弗·哈夫曼-拉罗切有限公司 | 作为p2x3拮抗剂的哌啶和哌嗪衍生物 |
| AU2006305104B2 (en) * | 2005-10-21 | 2009-10-22 | Mitsubishi Tanabe Pharma Corporation | Pyrazolo[1,5-a]pyrimidine compounds as cannabinoid receptor antagonists |
| CA2626789A1 (en) | 2005-10-21 | 2007-04-26 | Exelixis, Inc. | Pyrimidinones as casein kinase ii (ck2) modulators |
| WO2008054947A2 (en) | 2006-10-02 | 2008-05-08 | The Brigham And Women's Hospital, Inc. | Structure of acid beta-glucosidase and methods for identifying therapeutic agents |
| US20090275586A1 (en) | 2006-10-06 | 2009-11-05 | Kalypsys, Inc. | Heterocyclic inhibitors of pde4 |
| WO2008063671A2 (en) | 2006-11-20 | 2008-05-29 | Alantos Pharmaceuticals Holding, Inc. | Heterobicyclic metalloprotease inhibitors |
| US8399525B2 (en) | 2007-04-13 | 2013-03-19 | Amicus Therapeutics, Inc. | Treatment of gaucher disease with specific pharmacological chaperones and monitoring treatment using surrogate markers |
| US20090215778A1 (en) | 2007-04-27 | 2009-08-27 | Panacos Pharmaceuticals, Inc. | Alpha-substituted Arylmethyl Piperazine Pyrazolo [1,5-alpha]Pyrimidine Amide Derivatives |
| EP2154969B1 (en) | 2007-05-16 | 2015-11-18 | The Brigham and Women's Hospital, Inc. | Treatment of synucleinopathies |
| US20090118135A1 (en) | 2007-06-08 | 2009-05-07 | The Burnham Institute | Methods and compounds for regulating apoptosis |
| JP5337405B2 (ja) | 2007-09-17 | 2013-11-06 | ザ・ホスピタル・フォー・シック・チルドレン | ゴーシェ病の治療方法 |
| WO2009049422A1 (en) | 2007-10-18 | 2009-04-23 | The Hospital For Sick Children | Compositions and methods for enhancing enzyme activity in gaucher, gm1 -gangliosidosis/morquio b disease. and parkinson's disease |
| CA2709784A1 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| US8119637B2 (en) * | 2008-06-10 | 2012-02-21 | Plexxikon Inc. | Substituted pyrrolo[2,3-b]pyrazines and methods for kinase modulation, and indications therefor |
| WO2010003023A2 (en) * | 2008-07-01 | 2010-01-07 | Zacharon Pharmaceuticals, Inc. | Heparan sulfate inhibitors |
| WO2010086040A1 (en) | 2009-01-29 | 2010-08-05 | Biomarin Iga, Ltd. | Pyrazolo-pyrimidines for treatment of duchenne muscular dystrophy |
| DK2649075T3 (en) * | 2010-12-08 | 2018-07-30 | Us Health | SUBSTITUTED PYRAZOLOPYRIMIDINES AS GLUCOCEREBROSIDASE ACTIVATORS |
| HRP20240644T1 (hr) * | 2014-11-06 | 2024-08-02 | Bial-R&D Investments, S.A. | Supstituirani pirazolo(1,5-a)pirimidini i njihova uporaba u liječenju medicinskih poremećaja |
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