TWI670272B - 作為TRK激酶抑制劑之經取代吡唑并[1,5-a]嘧啶化合物 - Google Patents
作為TRK激酶抑制劑之經取代吡唑并[1,5-a]嘧啶化合物 Download PDFInfo
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- TWI670272B TWI670272B TW107124940A TW107124940A TWI670272B TW I670272 B TWI670272 B TW I670272B TW 107124940 A TW107124940 A TW 107124940A TW 107124940 A TW107124940 A TW 107124940A TW I670272 B TWI670272 B TW I670272B
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- Prior art keywords
- pyrazolo
- pyrrolidin
- pyrimidin
- fluorophenyl
- difluorophenyl
- Prior art date
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- 229940043355 kinase inhibitor Drugs 0.000 title abstract description 6
- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 6
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title description 149
- 150000001875 compounds Chemical class 0.000 claims abstract description 109
- 125000000217 alkyl group Chemical group 0.000 claims description 177
- -1 5-((R) -2- (2,5-difluorophenyl) pyrrolidin-1-yl) pyrazolo [1,5-a] pyrimidin-3-yl Chemical group 0.000 claims description 146
- 238000002360 preparation method Methods 0.000 claims description 95
- 125000001424 substituent group Chemical group 0.000 claims description 71
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 150000002367 halogens Chemical class 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 206010028980 Neoplasm Diseases 0.000 claims description 41
- 125000005842 heteroatom Chemical group 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 101150111783 NTRK1 gene Proteins 0.000 claims description 29
- 229910052731 fluorine Inorganic materials 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 27
- 101150056950 Ntrk2 gene Proteins 0.000 claims description 25
- 201000011510 cancer Diseases 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 19
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 11
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 206010027452 Metastases to bone Diseases 0.000 claims description 6
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 4
- 230000035772 mutation Effects 0.000 claims description 4
- NYNZQNWKBKUAII-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-KBXCAEBGSA-N 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
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- 101150117329 NTRK3 gene Proteins 0.000 claims description 3
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- 230000003321 amplification Effects 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 claims description 3
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- 238000003199 nucleic acid amplification method Methods 0.000 claims description 3
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- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- NYNZQNWKBKUAII-RDTXWAMCSA-N (3r)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-RDTXWAMCSA-N 0.000 claims description 2
- FSUQVGZSTAPXLA-DNVCBOLYSA-N (3r)-n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypiperidine-1-carboxamide Chemical compound C1[C@H](O)CCCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 FSUQVGZSTAPXLA-DNVCBOLYSA-N 0.000 claims description 2
- LIVISHFAOAESEN-RDTXWAMCSA-N (3r)-n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 LIVISHFAOAESEN-RDTXWAMCSA-N 0.000 claims description 2
- SDQDEHYSFKIQQB-DNVCBOLYSA-N (3r)-n-[5-[(2r)-2-[5-fluoro-2-(trifluoromethyl)phenyl]pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypiperidine-1-carboxamide Chemical compound C1[C@H](O)CCCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)C(F)(F)F)C=CN2N=C1 SDQDEHYSFKIQQB-DNVCBOLYSA-N 0.000 claims description 2
- FSUQVGZSTAPXLA-HNAYVOBHSA-N (3s)-n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypiperidine-1-carboxamide Chemical compound C1[C@@H](O)CCCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 FSUQVGZSTAPXLA-HNAYVOBHSA-N 0.000 claims description 2
- LIVISHFAOAESEN-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 LIVISHFAOAESEN-KBXCAEBGSA-N 0.000 claims description 2
- RGIQATAASXNYCK-QFBILLFUSA-N (3s)-n-[5-[(2r)-2-(5-fluoro-2-methoxyphenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypiperidine-1-carboxamide Chemical compound COC1=CC=C(F)C=C1[C@@H]1N(C2=NC3=C(NC(=O)N4C[C@@H](O)CCC4)C=NN3C=C2)CCC1 RGIQATAASXNYCK-QFBILLFUSA-N 0.000 claims description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- BJHSCJQTERBIFM-LJQANCHMSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-4-methylpiperazine-1-carboxamide Chemical compound C1CN(C)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 BJHSCJQTERBIFM-LJQANCHMSA-N 0.000 claims description 2
- NBXJYYGLFILKIE-GOSISDBHSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]morpholine-4-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)N4CCOCC4)C=NN3C=C2)=C1 NBXJYYGLFILKIE-GOSISDBHSA-N 0.000 claims description 2
- PDIREONSOPXOGN-GOSISDBHSA-N n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]morpholine-4-carboxamide Chemical compound FC1=CC=C(Cl)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)N4CCOCC4)C=NN3C=C2)=C1 PDIREONSOPXOGN-GOSISDBHSA-N 0.000 claims description 2
- 201000011519 neuroendocrine tumor Diseases 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 4
- ZUWQIFRIICXNQB-DNVCBOLYSA-N (3r)-n-[5-[(2r)-2-[2-(difluoromethyl)-5-fluorophenyl]pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypiperidine-1-carboxamide Chemical compound C1[C@H](O)CCCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)C(F)F)C=CN2N=C1 ZUWQIFRIICXNQB-DNVCBOLYSA-N 0.000 claims 1
- PXHANKVTFWSDSG-QLOBERJESA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 PXHANKVTFWSDSG-QLOBERJESA-N 0.000 claims 1
- UJDAFZWXQHLELA-OWRLQCHVSA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-methylpiperazine-1-carboxamide;hydrochloride Chemical compound Cl.C1CN[C@@H](C)CN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 UJDAFZWXQHLELA-OWRLQCHVSA-N 0.000 claims 1
- OEJMWAQAXCXMFH-FUHWJXTLSA-N (3s)-n-[5-[(2r)-2-(3-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C=C(Cl)C=C(F)C=3)C=CN2N=C1 OEJMWAQAXCXMFH-FUHWJXTLSA-N 0.000 claims 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
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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
- A61K31/495—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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/02—Ergot alkaloids of the cyclic peptide type
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
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- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US10761608P | 2008-10-22 | 2008-10-22 | |
| US61/107,616 | 2008-10-22 |
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| TW201835086A TW201835086A (zh) | 2018-10-01 |
| TWI670272B true TWI670272B (zh) | 2019-09-01 |
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| TW107124940A TWI670272B (zh) | 2008-10-22 | 2009-10-21 | 作為TRK激酶抑制劑之經取代吡唑并[1,5-a]嘧啶化合物 |
| TW103132675A TWI577680B (zh) | 2008-10-22 | 2009-10-21 | 作為TRK激酶抑制劑之經取代吡唑并〔1,5-a〕嘧啶化合物 |
| TW105143120A TWI639605B (zh) | 2008-10-22 | 2009-10-21 | 作為TRK激酶抑制劑之經取代吡唑并〔1,5-a〕嘧啶化合物 |
| TW098135670A TWI458729B (zh) | 2008-10-22 | 2009-10-21 | 作為TRK激酶抑制劑之經取代吡唑并〔1,5-a〕嘧啶化合物 |
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| TW103132675A TWI577680B (zh) | 2008-10-22 | 2009-10-21 | 作為TRK激酶抑制劑之經取代吡唑并〔1,5-a〕嘧啶化合物 |
| TW105143120A TWI639605B (zh) | 2008-10-22 | 2009-10-21 | 作為TRK激酶抑制劑之經取代吡唑并〔1,5-a〕嘧啶化合物 |
| TW098135670A TWI458729B (zh) | 2008-10-22 | 2009-10-21 | 作為TRK激酶抑制劑之經取代吡唑并〔1,5-a〕嘧啶化合物 |
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Families Citing this family (140)
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| SI2350075T1 (sl) | 2008-09-22 | 2014-06-30 | Array Biopharma, Inc. | Substituirane imidazo (1,2b)piridazinske spojine kot Trk kinazni inhibitorji |
| SG10201914059WA (en) | 2008-10-22 | 2020-03-30 | Array Biopharma Inc | Substituted pyrazolo[1,5-a]pyrimidine compounds as trk kinase inhibitors |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| TWI619713B (zh) | 2010-04-21 | 2018-04-01 | 普雷辛肯公司 | 用於激酶調節的化合物和方法及其適應症 |
| EP2918588B1 (en) | 2010-05-20 | 2017-05-03 | Array Biopharma, Inc. | Macrocyclic compounds as TRK kinase inhibitors |
| WO2012034095A1 (en) * | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| JP5959541B2 (ja) * | 2011-02-25 | 2016-08-02 | ノバルティス アーゲー | Trk阻害剤としてのピラゾロ[1,5−a]ピリジン |
| SI2712358T1 (sl) * | 2011-05-13 | 2017-03-31 | Array Biopharma, Inc. | Spojine pirolidinil sečnine, pirolidinil tiosečnine in pirolidinil gvanidina kot inhibitorji kinaze trka |
| WO2013088257A1 (en) | 2011-12-12 | 2013-06-20 | Dr. Reddy's Laboratories Ltd. | Substituted heterocyclic compounds as tropomyosin receptor kinase a (trka) inhibitors |
| PL2834243T3 (pl) * | 2012-03-09 | 2018-09-28 | Lexicon Pharmaceuticals, Inc. | Związki na bazie pirazolo[1,5-a]pirymidyny, zawierające je kompozycje i sposoby ich zastosowania |
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| US9790178B2 (en) | 2012-11-13 | 2017-10-17 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
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