JP2015500275A5 - - Google Patents
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- Publication number
- JP2015500275A5 JP2015500275A5 JP2014545388A JP2014545388A JP2015500275A5 JP 2015500275 A5 JP2015500275 A5 JP 2015500275A5 JP 2014545388 A JP2014545388 A JP 2014545388A JP 2014545388 A JP2014545388 A JP 2014545388A JP 2015500275 A5 JP2015500275 A5 JP 2015500275A5
- Authority
- JP
- Japan
- Prior art keywords
- pyridine
- pyrazolo
- carboxamide
- pyrrolidin
- difluorophenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 substituted Chemical class 0.000 claims description 385
- JVOGPCAZHXALIS-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1=CC=CC2=C(C(=O)N)C=NN21 JVOGPCAZHXALIS-UHFFFAOYSA-N 0.000 claims description 114
- 125000000217 alkyl group Chemical group 0.000 claims description 102
- 229910052736 halogen Inorganic materials 0.000 claims description 64
- 150000002367 halogens Chemical class 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 59
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 41
- 239000012453 solvate Substances 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 22
- 208000002193 Pain Diseases 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- 239000011734 sodium Substances 0.000 claims description 13
- 229910052708 sodium Inorganic materials 0.000 claims description 13
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 12
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 11
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 235000005152 nicotinamide Nutrition 0.000 claims description 10
- 239000011570 nicotinamide Substances 0.000 claims description 10
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 7
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 108091000080 Phosphotransferase Proteins 0.000 claims description 6
- 125000001475 halogen functional group Chemical group 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 102000020233 phosphotransferase Human genes 0.000 claims description 6
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 206010001935 American trypanosomiasis Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 208000024699 Chagas disease Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000016192 Demyelinating disease Diseases 0.000 claims description 4
- 206010012305 Demyelination Diseases 0.000 claims description 4
- 206010016654 Fibrosis Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 208000005615 Interstitial Cystitis Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 208000027418 Wounds and injury Diseases 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 4
- 230000004761 fibrosis Effects 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- LBMZPYPSOFPTCM-GOSISDBHSA-N 1-(2,5-dichlorothiophen-3-yl)sulfonyl-5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]-2H-pyrazolo[1,5-a]pyridine Chemical compound ClC=1SC(=CC=1S(=O)(=O)N1CC=C2N1C=CC(=C2)N1[C@H](CCC1)C1=C(C=CC(=C1)F)F)Cl LBMZPYPSOFPTCM-GOSISDBHSA-N 0.000 claims description 3
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 claims description 3
- UDWJEOZAPNDSIL-SWLSCSKDSA-N 4-fluoro-5-[(2r,4s)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl]-n-sulfamoylpyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2C[C@H](F)CN2C=2C=CN3N=CC(=C3C=2F)C(=O)NS(=O)(=O)N)=CC=CC(F)=C1 UDWJEOZAPNDSIL-SWLSCSKDSA-N 0.000 claims description 3
- BPDCLEMIYBBLFM-MEDUHNTESA-N 5-[(2R,4S)-2-(2,5-difluorophenyl)-4-fluoropyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1[C@@H](CN([C@H]1C2=C(C=CC(=C2)F)F)C3=CC4=C(C=NN4C=C3)C(=O)N)F BPDCLEMIYBBLFM-MEDUHNTESA-N 0.000 claims description 3
- SJCJZSQLSWJXKM-JOCHJYFZSA-N 5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]-n-(4-fluorophenyl)sulfonylpyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1=CC(F)=CC=C1S(=O)(=O)NC(=O)C1=C2C=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 SJCJZSQLSWJXKM-JOCHJYFZSA-N 0.000 claims description 3
- CIWGHCHQCWQQPV-MRXNPFEDSA-N 5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]-n-sulfamoylpyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3C=2)C(=O)NS(=O)(=O)N)=CC(F)=CC=C1F CIWGHCHQCWQQPV-MRXNPFEDSA-N 0.000 claims description 3
- 208000008035 Back Pain Diseases 0.000 claims description 3
- 206010006002 Bone pain Diseases 0.000 claims description 3
- FUOGXIZNLDFJBB-UHFFFAOYSA-N C1CC(N(C1)C2=C(C3=C(C=NN3C=C2)C(=O)N)F)C4=CC(=CC=C4)F Chemical compound C1CC(N(C1)C2=C(C3=C(C=NN3C=C2)C(=O)N)F)C4=CC(=CC=C4)F FUOGXIZNLDFJBB-UHFFFAOYSA-N 0.000 claims description 3
- VEWVKZTUGFFYAK-OAQYLSRUSA-N CC(N=C(C)S1)=C1S(N1N(C=CC(N(CCC2)[C@H]2C(C=C(C=C2)F)=C2F)=C2)C2=CC1)(=O)=O Chemical compound CC(N=C(C)S1)=C1S(N1N(C=CC(N(CCC2)[C@H]2C(C=C(C=C2)F)=C2F)=C2)C2=CC1)(=O)=O VEWVKZTUGFFYAK-OAQYLSRUSA-N 0.000 claims description 3
- 208000000094 Chronic Pain Diseases 0.000 claims description 3
- 208000000668 Chronic Pancreatitis Diseases 0.000 claims description 3
- 206010011796 Cystitis interstitial Diseases 0.000 claims description 3
- 206010065390 Inflammatory pain Diseases 0.000 claims description 3
- 208000008930 Low Back Pain Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 208000019695 Migraine disease Diseases 0.000 claims description 3
- BPDCLEMIYBBLFM-BDJLRTHQSA-N NC(=O)c1cnn2ccc(cc12)N1C[C@H](F)C[C@@H]1c1cc(F)ccc1F Chemical compound NC(=O)c1cnn2ccc(cc12)N1C[C@H](F)C[C@@H]1c1cc(F)ccc1F BPDCLEMIYBBLFM-BDJLRTHQSA-N 0.000 claims description 3
- SHRMEYWTWVCTMD-AREMUKBSSA-N O=S(C1(CC(C=C2)=CC=C2F)CC1)(N1N(C=CC(N(CCC2)[C@H]2C(C=C(C=C2)F)=C2F)=C2)C2=CC1)=O Chemical compound O=S(C1(CC(C=C2)=CC=C2F)CC1)(N1N(C=CC(N(CCC2)[C@H]2C(C=C(C=C2)F)=C2F)=C2)C2=CC1)=O SHRMEYWTWVCTMD-AREMUKBSSA-N 0.000 claims description 3
- 206010033649 Pancreatitis chronic Diseases 0.000 claims description 3
- 108091005682 Receptor kinases Proteins 0.000 claims description 3
- 102000005937 Tropomyosin Human genes 0.000 claims description 3
- 108010030743 Tropomyosin Proteins 0.000 claims description 3
- CSYLTZQSWCQYJT-FSRHSHDFSA-M [Na+].CC(C)(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)ccc1F Chemical compound [Na+].CC(C)(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)ccc1F CSYLTZQSWCQYJT-FSRHSHDFSA-M 0.000 claims description 3
- RIHRGBWZQXPLEZ-FSRHSHDFSA-M [Na+].CC1(CC1)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)ccc1F Chemical compound [Na+].CC1(CC1)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)ccc1F RIHRGBWZQXPLEZ-FSRHSHDFSA-M 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 208000005298 acute pain Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- 206010027599 migraine Diseases 0.000 claims description 3
- 230000023105 myelination Effects 0.000 claims description 3
- ROHOODBFOCKURX-XMMPIXPASA-N n-(3-cyanophenyl)sulfonyl-5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]-n-methylpyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3C=2)C(=O)N(C)S(=O)(=O)C=2C=C(C=CC=2)C#N)=CC(F)=CC=C1F ROHOODBFOCKURX-XMMPIXPASA-N 0.000 claims description 3
- GKJDQZUINMXDSN-QGZVFWFLSA-N n-tert-butylsulfonyl-5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]-4-fluoropyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3C=2F)C(=O)NS(=O)(=O)C(C)(C)C)=CC(F)=CC=C1F GKJDQZUINMXDSN-QGZVFWFLSA-N 0.000 claims description 3
- XOSJIAUDQHQJGW-LJQANCHMSA-N n-tert-butylsulfonyl-5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3C=2)C(=O)NS(=O)(=O)C(C)(C)C)=CC(F)=CC=C1F XOSJIAUDQHQJGW-LJQANCHMSA-N 0.000 claims description 3
- PSGMHTNJMIJUOJ-MRXNPFEDSA-N n-tert-butylsulfonyl-5-[(2r)-2-[2-(difluoromethoxy)-5-fluorophenyl]pyrrolidin-1-yl]-4-fluoropyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3C=2F)C(=O)NS(=O)(=O)C(C)(C)C)=CC(F)=CC=C1OC(F)F PSGMHTNJMIJUOJ-MRXNPFEDSA-N 0.000 claims description 3
- 208000004296 neuralgia Diseases 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 208000021722 neuropathic pain Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical compound CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 claims description 3
- JLFSSZWHTVMTQM-VZYDHVRKSA-M sodium [5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]-(2-methylphenyl)sulfonylazanide Chemical compound [Na+].Cc1ccccc1S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)ccc1F JLFSSZWHTVMTQM-VZYDHVRKSA-M 0.000 claims description 3
- NFCHKNAWTLINPV-GMUIIQOCSA-M sodium [5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]-(dimethylsulfamoyl)azanide Chemical compound [Na+].CN(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)ccc1F NFCHKNAWTLINPV-GMUIIQOCSA-M 0.000 claims description 3
- GJVIWXQKOUDAAF-OWRLQCHVSA-M sodium [5-[(2R,4S)-2-(2,5-difluorophenyl)-4-fluoropyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]-(1-methylcyclopropyl)sulfonylazanide Chemical compound [Na+].CC1(CC1)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1C[C@@H](F)C[C@@H]1c1cc(F)ccc1F GJVIWXQKOUDAAF-OWRLQCHVSA-M 0.000 claims description 3
- MVHIDLZJWRAORT-UFRBEDTPSA-M sodium [5-[(2R,4S)-2-(2,5-difluorophenyl)-4-fluoropyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]-(dimethylsulfamoyl)azanide Chemical compound [Na+].CN(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1C[C@@H](F)C[C@@H]1c1cc(F)ccc1F MVHIDLZJWRAORT-UFRBEDTPSA-M 0.000 claims description 3
- ZBFPJVIMVHBMJJ-YBRRAQHRSA-M sodium [ethyl(methyl)sulfamoyl]-[5-[(2R)-2-[5-fluoro-2-(oxolan-3-yloxy)phenyl]pyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]azanide Chemical compound [Na+].CCN(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)ccc1OC1CCOC1 ZBFPJVIMVHBMJJ-YBRRAQHRSA-M 0.000 claims description 3
- HRQXCRZBKGBWGT-QVNYQEOOSA-M sodium tert-butylsulfonyl-[4-fluoro-5-[(2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]azanide Chemical compound [Na+].CC(C)(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(N3C[C@@H](F)C[C@@H]3c3cccc(F)c3)c(F)c12 HRQXCRZBKGBWGT-QVNYQEOOSA-M 0.000 claims description 3
- ILAQROQVKANYSL-HNPYGVFOSA-M sodium tert-butylsulfonyl-[5-[(2R)-2-(2,5-difluorophenyl)-4-fluoropyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]azanide Chemical compound [Na+].CC(C)(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CC(F)C[C@@H]1c1cc(F)ccc1F ILAQROQVKANYSL-HNPYGVFOSA-M 0.000 claims description 3
- RTWJPSQGAJYCAK-FSRHSHDFSA-M sodium tert-butylsulfonyl-[5-[(2R)-2-(7-fluoro-2,3-dihydro-1,4-benzodioxin-5-yl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]azanide Chemical compound [Na+].CC(C)(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CCC[C@@H]1c1cc(F)cc2OCCOc12 RTWJPSQGAJYCAK-FSRHSHDFSA-M 0.000 claims description 3
- HRQZTLZOTCSEII-UHFFFAOYSA-M sodium tert-butylsulfonyl-[5-[2-(2,5-difluorophenyl)-4,4-difluoropyrrolidin-1-yl]pyrazolo[1,5-a]pyridine-3-carbonyl]azanide Chemical compound [Na+].CC(C)(C)S(=O)(=O)[N-]C(=O)c1cnn2ccc(cc12)N1CC(F)(F)CC1c1cc(F)ccc1F HRQZTLZOTCSEII-UHFFFAOYSA-M 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 208000009935 visceral pain Diseases 0.000 claims description 3
- JAIKYSIWFPWFLJ-UHFFFAOYSA-N N-propan-2-ylsulfonylpyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound CC(C)S(=O)(=O)NC(=O)c1cnn2ccccc12 JAIKYSIWFPWFLJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 4
- 201000003146 cystitis Diseases 0.000 claims 2
- ORGBMOYOSFKVRB-ZUZCIYMTSA-N 5-[(2R,4S)-2-(2,5-difluorophenyl)-4-fluoropyrrolidin-1-yl]-4-fluoro-N-sulfamoylpyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound FC1=C(C=C(C=C1)F)[C@@H]1N(C[C@H](C1)F)C1=C(C=2N(C=C1)N=CC=2C(=O)NS(N)(=O)=O)F ORGBMOYOSFKVRB-ZUZCIYMTSA-N 0.000 claims 1
- KGCLKVAYUVPSKS-SCLBCKFNSA-N 5-[(2R,4S)-2-(2,5-difluorophenyl)-4-fluoropyrrolidin-1-yl]-N-[ethyl(methyl)sulfamoyl]-4-fluoropyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound FC1=C(C=C(C=C1)F)[C@@H]1N(C[C@H](C1)F)C1=C(C=2N(C=C1)N=CC=2C(=O)NS(N(C)CC)(=O)=O)F KGCLKVAYUVPSKS-SCLBCKFNSA-N 0.000 claims 1
- YTSZJDMTUXVEIM-MGPUTAFESA-N 5-[(2r,4s)-2-(2-cyclopropyloxy-5-fluorophenyl)-4-fluoropyrrolidin-1-yl]-n-[ethyl(methyl)sulfamoyl]-4-fluoropyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2C[C@H](F)CN2C=2C=CN3N=CC(=C3C=2F)C(=O)NS(=O)(=O)N(C)CC)=CC(F)=CC=C1OC1CC1 YTSZJDMTUXVEIM-MGPUTAFESA-N 0.000 claims 1
- CCWGDGSJPPFLAT-LAUBAEHRSA-N 5-[(2r,4s)-2-[2-(cyclopropylmethoxy)-5-fluorophenyl]-4-fluoropyrrolidin-1-yl]-n-[ethyl(methyl)sulfamoyl]-4-fluoropyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1([C@H]2C[C@H](F)CN2C=2C=CN3N=CC(=C3C=2F)C(=O)NS(=O)(=O)N(C)CC)=CC(F)=CC=C1OCC1CC1 CCWGDGSJPPFLAT-LAUBAEHRSA-N 0.000 claims 1
- BOAIQGZPTHEQDX-SCLBCKFNSA-N C(C)(C)(C)S(=O)(=O)NC(=O)C=1C=NN2C=1C(=C(C=C2)N1[C@H](C[C@@H](C1)F)C1=C(C=CC(=C1)F)F)F Chemical compound C(C)(C)(C)S(=O)(=O)NC(=O)C=1C=NN2C=1C(=C(C=C2)N1[C@H](C[C@@H](C1)F)C1=C(C=CC(=C1)F)F)F BOAIQGZPTHEQDX-SCLBCKFNSA-N 0.000 claims 1
- GHWSKZIAWFUMHD-YVEFUNNKSA-N FC1=C(C=C(C=C1)F)[C@@H]1N(C[C@H](C1)F)C1=C(C=2N(C=C1)N=CC=2C(=O)NS(N(C)C)(=O)=O)F Chemical compound FC1=C(C=C(C=C1)F)[C@@H]1N(C[C@H](C1)F)C1=C(C=2N(C=C1)N=CC=2C(=O)NS(N(C)C)(=O)=O)F GHWSKZIAWFUMHD-YVEFUNNKSA-N 0.000 claims 1
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| WO2012116217A1 (en) * | 2011-02-25 | 2012-08-30 | Irm Llc | Compounds and compositions as trk inhibitors |
| KR20140105508A (ko) * | 2011-12-12 | 2014-09-01 | 닥터 레디스 레보러터리즈 리미티드 | 트로포미오신 수용체 키나제(Trk) 억제제인 치환된 피라졸로[1,5-a]피리딘 |
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2012
- 2012-12-12 KR KR1020147018107A patent/KR20140105508A/ko not_active Ceased
- 2012-12-12 WO PCT/IB2012/003012 patent/WO2013088256A1/en not_active Ceased
- 2012-12-12 MX MX2014006980A patent/MX356401B/es active IP Right Grant
- 2012-12-12 EA EA201400701A patent/EA025352B1/ru not_active IP Right Cessation
- 2012-12-12 CA CA2858958A patent/CA2858958C/en not_active Expired - Fee Related
- 2012-12-12 WO PCT/IB2012/003022 patent/WO2013088257A1/en not_active Ceased
- 2012-12-12 US US14/364,518 patent/US9045479B2/en not_active Expired - Fee Related
- 2012-12-12 EP EP12834589.9A patent/EP2791139B1/en not_active Not-in-force
- 2012-12-12 DK DK12832784.8T patent/DK2791138T3/en active
- 2012-12-12 EP EP12832784.8A patent/EP2791138B1/en not_active Not-in-force
- 2012-12-12 KR KR1020177000318A patent/KR101849143B1/ko not_active Expired - Fee Related
- 2012-12-12 BR BR112014014276A patent/BR112014014276A2/pt not_active IP Right Cessation
- 2012-12-12 CN CN201280069575.8A patent/CN104114553B/zh not_active Expired - Fee Related
- 2012-12-12 US US14/364,451 patent/US9045478B2/en not_active Expired - Fee Related
- 2012-12-12 JP JP2014545388A patent/JP5990595B2/ja not_active Expired - Fee Related
- 2012-12-12 ES ES12832784T patent/ES2686501T3/es active Active
- 2012-12-12 AU AU2012351748A patent/AU2012351748B2/en not_active Ceased
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2014
- 2014-06-10 IL IL233067A patent/IL233067B/en active IP Right Grant
- 2014-06-11 CL CL2014001529A patent/CL2014001529A1/es unknown
- 2014-06-26 CO CO14137528A patent/CO7071124A2/es active IP Right Grant
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2015
- 2015-02-26 US US14/632,078 patent/US9289419B2/en not_active Expired - Fee Related
- 2015-05-29 US US14/725,683 patent/US9402833B2/en not_active Expired - Fee Related
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2016
- 2016-05-25 US US15/164,430 patent/US9670207B2/en not_active Expired - Fee Related
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2017
- 2017-06-01 US US15/611,203 patent/US10047087B2/en not_active Expired - Fee Related
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2018
- 2018-08-13 US US16/101,753 patent/US10344031B2/en not_active Expired - Fee Related
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