KR20080043383A - Ｆａｐ 저해제 - Google Patents
Ｆａｐ 저해제 Download PDFInfo
- Publication number
- KR20080043383A KR20080043383A KR1020087007975A KR20087007975A KR20080043383A KR 20080043383 A KR20080043383 A KR 20080043383A KR 1020087007975 A KR1020087007975 A KR 1020087007975A KR 20087007975 A KR20087007975 A KR 20087007975A KR 20080043383 A KR20080043383 A KR 20080043383A
- Authority
- KR
- South Korea
- Prior art keywords
- pyrrolidine
- carbonitrile
- mmol
- methoxybenzoylamino
- alkyl
- 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.)
- Withdrawn
Links
- 239000003112 inhibitor Substances 0.000 title description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 142
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 23
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 201000011510 cancer Diseases 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims description 51
- -1 (C 1 C 4) alkyl Compound Chemical class 0.000 claims description 27
- ALSCEGDXFJIYES-UHFFFAOYSA-N pyrrolidine-2-carbonitrile Chemical compound N#CC1CCCN1 ALSCEGDXFJIYES-UHFFFAOYSA-N 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 206010016654 Fibrosis Diseases 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 8
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 7
- 230000035755 proliferation Effects 0.000 claims description 7
- 206010027476 Metastases Diseases 0.000 claims description 5
- 208000007502 anemia Diseases 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 210000000601 blood cell Anatomy 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 230000004761 fibrosis Effects 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 230000003211 malignant effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 208000004235 neutropenia Diseases 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- VEBQYHFHXCAREJ-UHFFFAOYSA-N pyrrolidin-2-ylboronic acid Chemical compound OB(O)C1CCCN1 VEBQYHFHXCAREJ-UHFFFAOYSA-N 0.000 claims description 5
- 230000029663 wound healing Effects 0.000 claims description 5
- 208000016216 Choristoma Diseases 0.000 claims description 4
- 208000034189 Sclerosis Diseases 0.000 claims description 4
- 230000007882 cirrhosis Effects 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 238000007634 remodeling Methods 0.000 claims description 4
- OAKKEQGCYJDXOZ-BWESVNLHSA-O CCC(C)[C@@H](C([S+](C1)CN[C@@H]1C#N)=O)NC(C1=CC=CC(OC)=C1)=O Chemical compound CCC(C)[C@@H](C([S+](C1)CN[C@@H]1C#N)=O)NC(C1=CC=CC(OC)=C1)=O OAKKEQGCYJDXOZ-BWESVNLHSA-O 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- MMEPVYJSHWWBSV-HNNXBMFYSA-N n-[2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]-2-methoxy-n-(2-methylpropyl)benzamide Chemical compound COC1=CC=CC=C1C(=O)N(CC(C)C)CC(=O)N1[C@H](C#N)CCC1 MMEPVYJSHWWBSV-HNNXBMFYSA-N 0.000 claims description 3
- JWFDLILYICVSFH-UHFFFAOYSA-N 1,1-dioxo-1,3-thiazolidine-4-carbonitrile Chemical compound O=S1(=O)CNC(C#N)C1 JWFDLILYICVSFH-UHFFFAOYSA-N 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 230000008467 tissue growth Effects 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 150000007649 L alpha amino acids Chemical class 0.000 claims 4
- 239000011159 matrix material Substances 0.000 claims 3
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 125000003709 fluoroalkyl group Chemical group 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- BHPWUBNBWJDBRI-GJZGRUSLSA-N (2s)-1-[(2s)-1-(3-chlorobenzoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound ClC1=CC=CC(C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C#N)=C1 BHPWUBNBWJDBRI-GJZGRUSLSA-N 0.000 claims 1
- VDBOVPXABUSAOH-HOCLYGCPSA-N (2s)-1-[(2s)-1-(3-methoxybenzoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbaldehyde Chemical compound COC1=CC=CC(C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C=O)=C1 VDBOVPXABUSAOH-HOCLYGCPSA-N 0.000 claims 1
- VGPPINZLYPNBTM-HOCLYGCPSA-N (2s)-1-[(2s)-1-(3-methoxybenzoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC=CC(C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C#N)=C1 VGPPINZLYPNBTM-HOCLYGCPSA-N 0.000 claims 1
- ZERXNNPHBAEGND-HOTGVXAUSA-N (2s)-1-[(2s)-1-benzoylpiperidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound C([C@H]1C(=O)N2[C@@H](CCC2)C#N)CCCN1C(=O)C1=CC=CC=C1 ZERXNNPHBAEGND-HOTGVXAUSA-N 0.000 claims 1
- DUAMOTNTPOWUPE-VWHLVEDXSA-N (2s)-1-[(2s)-2-(2-methoxybenzoyl)-1,3,3a,4,5,6,7,7a-octahydroindole-2-carbonyl]pyrrolidine-2-carbaldehyde Chemical compound COC1=CC=CC=C1C(=O)[C@@]1(C(=O)N2[C@@H](CCC2)C=O)NC2CCCCC2C1 DUAMOTNTPOWUPE-VWHLVEDXSA-N 0.000 claims 1
- HOGMKLFVXPLGIF-HKDCCESQSA-N (2s)-1-[(2s)-2-(4-methylbenzoyl)-1,3,3a,4,5,6,7,7a-octahydroindole-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound C1=CC(C)=CC=C1C(=O)[C@@]1(C(=O)N2[C@@H](CCC2)C#N)NC2CCCCC2C1 HOGMKLFVXPLGIF-HKDCCESQSA-N 0.000 claims 1
- DQLWFRJPQSKXMX-UWVGGRQHSA-N (2s)-2-[(2s)-2-cyano-4,4-difluoropyrrolidine-1-carbonyl]-n-ethylpyrrolidine-1-carboxamide Chemical compound CCNC(=O)N1CCC[C@H]1C(=O)N1[C@H](C#N)CC(F)(F)C1 DQLWFRJPQSKXMX-UWVGGRQHSA-N 0.000 claims 1
- HUCDGWFIFAEIHW-VSUJBEPISA-N (2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-n-ethyl-1,3,3a,4,5,6,7,7a-octahydroindole-2-carboxamide Chemical compound O=C([C@@]1(NC2CCCCC2C1)C(=O)NCC)N1CCC[C@H]1C#N HUCDGWFIFAEIHW-VSUJBEPISA-N 0.000 claims 1
- HBSIJYHNQSYMFP-RYUDHWBXSA-N (2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-n-propan-2-ylpyrrolidine-1-carboxamide Chemical compound CC(C)NC(=O)N1CCC[C@H]1C(=O)N1[C@H](C#N)CCC1 HBSIJYHNQSYMFP-RYUDHWBXSA-N 0.000 claims 1
- AZTYKQXGOBGTPX-RYUDHWBXSA-N (2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-n-propylpyrrolidine-1-carbothioamide Chemical compound CCCNC(=S)N1CCC[C@H]1C(=O)N1[C@H](C#N)CCC1 AZTYKQXGOBGTPX-RYUDHWBXSA-N 0.000 claims 1
- FQULOSOYTBNLIJ-SHWKFHJASA-N (2s)-n-ethyl-2-[(2s)-2-formylpyrrolidine-1-carbonyl]-2,3,3a,4,5,6,7,7a-octahydroindole-1-carboxamide Chemical compound O=C([C@@H]1CC2CCCCC2N1C(=O)NCC)N1CCC[C@H]1C=O FQULOSOYTBNLIJ-SHWKFHJASA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- CBEFQPARQNDBRR-UWVGGRQHSA-N 1-[(2s)-1-[(2s)-2-cyano-4,4-difluoropyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-ethylurea Chemical compound CCNC(=O)N[C@@H](C(C)C)C(=O)N1CC(F)(F)C[C@H]1C#N CBEFQPARQNDBRR-UWVGGRQHSA-N 0.000 claims 1
- HLNHLDNAGJUUKD-HOTGVXAUSA-N 1-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-3-propan-2-ylurea Chemical compound C([C@H](NC(=O)NC(C)C)C(=O)N1[C@@H](CCC1)C#N)C1=CC=CC=C1 HLNHLDNAGJUUKD-HOTGVXAUSA-N 0.000 claims 1
- CQPKYTAFAQYZBS-UWVGGRQHSA-N 1-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-1-oxopropan-2-yl]-3-propan-2-ylurea Chemical compound CC(C)NC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C#N CQPKYTAFAQYZBS-UWVGGRQHSA-N 0.000 claims 1
- ZSCRPXVYYFXEHH-QWRGUYRKSA-N 1-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-ethylurea Chemical compound CCNC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C#N ZSCRPXVYYFXEHH-QWRGUYRKSA-N 0.000 claims 1
- FTTUJTGRYWOXDJ-BEEDKBRMSA-N 1-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-3-(2-phenylethyl)thiourea Chemical compound N([C@@H](C(C)CC)C(=O)N1[C@@H](CCC1)C#N)C(=S)NCCC1=CC=CC=C1 FTTUJTGRYWOXDJ-BEEDKBRMSA-N 0.000 claims 1
- BUNPRTJDEIFBRC-RAMGSTBQSA-N 1-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-3-ethylurea Chemical compound CCNC(=O)N[C@@H](C(C)CC)C(=O)N1CCC[C@H]1C#N BUNPRTJDEIFBRC-RAMGSTBQSA-N 0.000 claims 1
- DNZCDLDJXZSDAH-STQMWFEESA-N 1-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]-3-ethyl-1-methylurea Chemical compound CCNC(=O)N(C)[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C#N DNZCDLDJXZSDAH-STQMWFEESA-N 0.000 claims 1
- QDPLHRWMRWAAAC-JKSUJKDBSA-N 1-benzyl-3-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]urea Chemical compound N([C@@H](C(C)(C)C)C(=O)N1[C@@H](CCC1)C#N)C(=O)NCC1=CC=CC=C1 QDPLHRWMRWAAAC-JKSUJKDBSA-N 0.000 claims 1
- RNQZZHMEFRITHS-VYIIXAMBSA-N 2-methoxy-n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylpentan-2-yl]benzamide Chemical compound N([C@@H](C(C)CC)C(=O)N1CCCC1)C(=O)C1=CC=CC=C1OC RNQZZHMEFRITHS-VYIIXAMBSA-N 0.000 claims 1
- 239000004475 Arginine Substances 0.000 claims 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 1
- DNRDOVSZCGLLGT-TUJLOAKASA-N N([C@@H](C(C)CC)C(=O)S1(=O)C[C@H](NC1)C#N)C(=O)C1=CC=CC(OC)=C1 Chemical compound N([C@@H](C(C)CC)C(=O)S1(=O)C[C@H](NC1)C#N)C(=O)C1=CC=CC(OC)=C1 DNRDOVSZCGLLGT-TUJLOAKASA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- ANPJLJNEFJVWOO-GJZGRUSLSA-N [(2r)-1-[(2s)-2-[(2-methoxybenzoyl)amino]-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound COC1=CC=CC=C1C(=O)N[C@@H](C(C)C)C(=O)N1[C@H](B(O)O)CCC1 ANPJLJNEFJVWOO-GJZGRUSLSA-N 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 1
- DDHODFLDJUQHSX-SFTDATJTSA-N benzyl (4s)-4-[(4-chlorobenzoyl)amino]-5-[(2s)-2-cyanopyrrolidin-1-yl]-5-oxopentanoate Chemical compound C1=CC(Cl)=CC=C1C(=O)N[C@H](C(=O)N1[C@@H](CCC1)C#N)CCC(=O)OCC1=CC=CC=C1 DDHODFLDJUQHSX-SFTDATJTSA-N 0.000 claims 1
- QFDOFQHDZCGZJQ-ICSRJNTNSA-N benzyl n-[(2s)-3-[(2s)-2-cyanopyrrolidin-1-yl]-2-[(2-methoxybenzoyl)amino]-3-oxopropyl]carbamate Chemical compound COC1=CC=CC=C1C(=O)N[C@H](C(=O)N1[C@@H](CCC1)C#N)CNC(=O)OCC1=CC=CC=C1 QFDOFQHDZCGZJQ-ICSRJNTNSA-N 0.000 claims 1
- BAKBWMQUYIHULH-FPOVZHCZSA-N benzyl n-[(3s)-4-[(2s)-2-cyanopyrrolidin-1-yl]-3-[(2-methoxybenzoyl)amino]-4-oxobutyl]carbamate Chemical compound COC1=CC=CC=C1C(=O)N[C@H](C(=O)N1[C@@H](CCC1)C#N)CCNC(=O)OCC1=CC=CC=C1 BAKBWMQUYIHULH-FPOVZHCZSA-N 0.000 claims 1
- WBTNMOUDIQEVFC-GMAHTHKFSA-N benzyl n-[(4s)-5-[(2s)-2-cyanopyrrolidin-1-yl]-4-[(4-methoxybenzoyl)amino]-5-oxopentyl]carbamate Chemical compound C1=CC(OC)=CC=C1C(=O)N[C@H](C(=O)N1[C@@H](CCC1)C#N)CCCNC(=O)OCC1=CC=CC=C1 WBTNMOUDIQEVFC-GMAHTHKFSA-N 0.000 claims 1
- AQFRZEWKJVGQGN-UPVQGACJSA-N benzyl n-[(5s)-6-[(2s)-2-cyanopyrrolidin-1-yl]-5-[(3-methoxybenzoyl)amino]-6-oxohexyl]carbamate Chemical compound COC1=CC=CC(C(=O)N[C@@H](CCCCNC(=O)OCC=2C=CC=CC=2)C(=O)N2[C@@H](CCC2)C#N)=C1 AQFRZEWKJVGQGN-UPVQGACJSA-N 0.000 claims 1
- FAUWKACRJDTPOA-JSGCOSHPSA-N methyl (3s)-4-[(2s)-2-cyanopyrrolidin-1-yl]-3-[(2-methoxybenzoyl)amino]-4-oxobutanoate Chemical compound N([C@@H](CC(=O)OC)C(=O)N1[C@@H](CCC1)C#N)C(=O)C1=CC=CC=C1OC FAUWKACRJDTPOA-JSGCOSHPSA-N 0.000 claims 1
- VCEGEGIPEXYJAI-HKUYNNGSSA-N n-[(1s)-2-[(2s)-2-cyanopyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)N[C@H](C(=O)N1[C@@H](CCC1)C#N)C1CCCCC1 VCEGEGIPEXYJAI-HKUYNNGSSA-N 0.000 claims 1
- PWTSYTVTZMZJGD-ROUUACIJSA-N n-[(1s)-2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxo-1-phenylethyl]cyclohexanecarboxamide Chemical compound O=C([C@@H](NC(=O)C1CCCCC1)C=1C=CC=CC=1)N1CCC[C@H]1C#N PWTSYTVTZMZJGD-ROUUACIJSA-N 0.000 claims 1
- UVUCACZVILCRPP-WFASDCNBSA-N n-[(2s)-1-[(2s)-2-cyano-4,4-difluoropyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(=O)N[C@@H](C(C)C)C(=O)N1[C@H](C#N)CC(F)(F)C1 UVUCACZVILCRPP-WFASDCNBSA-N 0.000 claims 1
- RGZBPLPCOYHYKX-XGFYENRKSA-N n-[(2s)-1-[(2s)-2-cyanoazetidin-1-yl]-3-methyl-1-oxopentan-2-yl]-2-methoxybenzamide Chemical compound N([C@@H](C(C)CC)C(=O)N1[C@@H](CC1)C#N)C(=O)C1=CC=CC=C1OC RGZBPLPCOYHYKX-XGFYENRKSA-N 0.000 claims 1
- QVOUOWQMLYUBSG-UFFKYAFASA-N n-[(2s)-1-[(2s)-2-cyanopiperidin-1-yl]-3-methyl-1-oxopentan-2-yl]-2-methoxybenzamide Chemical compound N([C@@H](C(C)CC)C(=O)N1[C@@H](CCCC1)C#N)C(=O)C1=CC=CC=C1OC QVOUOWQMLYUBSG-UFFKYAFASA-N 0.000 claims 1
- IRXQLUZQSXKQTK-PMACEKPBSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-1-oxo-3-phenylmethoxypropan-2-yl]benzamide Chemical compound C([C@H](NC(=O)C=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C#N)OCC1=CC=CC=C1 IRXQLUZQSXKQTK-PMACEKPBSA-N 0.000 claims 1
- VJKYBUCABNMHNZ-HOTGVXAUSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-2,2-dimethylpropanamide Chemical compound C([C@H](NC(=O)C(C)(C)C)C(=O)N1[C@@H](CCC1)C#N)C1=CC=CC=C1 VJKYBUCABNMHNZ-HOTGVXAUSA-N 0.000 claims 1
- NEKKARWFODQEBP-PMACEKPBSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-n-methylcyclohexanecarboxamide Chemical compound C([C@H](N(C)C(=O)C1CCCCC1)C(=O)N1[C@@H](CCC1)C#N)C1=CC=CC=C1 NEKKARWFODQEBP-PMACEKPBSA-N 0.000 claims 1
- CNDNFODYJHUFBN-JSGCOSHPSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-1-oxopropan-2-yl]-n-methylcyclohexanecarboxamide Chemical compound CN([C@@H](C)C(=O)N1[C@@H](CCC1)C#N)C(=O)C1CCCCC1 CNDNFODYJHUFBN-JSGCOSHPSA-N 0.000 claims 1
- RANABWAAQNNYCJ-XJKSGUPXSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(=O)N[C@@H](C(C)(C)C)C(=O)N1[C@H](C#N)CCC1 RANABWAAQNNYCJ-XJKSGUPXSA-N 0.000 claims 1
- BUMFFFVUHIJEKL-HOCLYGCPSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)N[C@@H](C(C)C)C(=O)N2[C@@H](CCC2)C#N)=C1 BUMFFFVUHIJEKL-HOCLYGCPSA-N 0.000 claims 1
- MZHFTMRPFYCUDY-SPOOISQMSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)N[C@@H](C(C)CC)C(=O)N1CCC[C@H]1C#N MZHFTMRPFYCUDY-SPOOISQMSA-N 0.000 claims 1
- FJGNQUANKGZDDK-UFFKYAFASA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-2-methoxy-n-methylbenzamide Chemical compound CN([C@@H](C(C)CC)C(=O)N1[C@@H](CCC1)C#N)C(=O)C1=CC=CC=C1OC FJGNQUANKGZDDK-UFFKYAFASA-N 0.000 claims 1
- FAWMMKSJLIZZRH-HUUYTVAOSA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-2-methoxybenzamide Chemical compound N([C@@H](C(C)CC)C(=O)N1[C@@H](CCC1)C#N)C(=O)C1=CC=CC=C1OC FAWMMKSJLIZZRH-HUUYTVAOSA-N 0.000 claims 1
- DEGBUCDMCRUTQK-QJOPWCIASA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-3-methoxybenzamide Chemical compound N([C@@H](C(C)CC)C(=O)N1[C@@H](CCC1)C#N)C(=O)C1=CC=CC(OC)=C1 DEGBUCDMCRUTQK-QJOPWCIASA-N 0.000 claims 1
- AUPWEHXGXJUQRD-QJOPWCIASA-N n-[(2s)-1-[(2s)-2-cyanopyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-4-methoxybenzamide Chemical compound N([C@@H](C(C)CC)C(=O)N1[C@@H](CCC1)C#N)C(=O)C1=CC=C(OC)C=C1 AUPWEHXGXJUQRD-QJOPWCIASA-N 0.000 claims 1
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Classifications
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71332405P | 2005-09-02 | 2005-09-02 | |
| EP05108049A EP1760076A1 (en) | 2005-09-02 | 2005-09-02 | FAP Inhibitors |
| EP05108049.7 | 2005-09-02 | ||
| US60/713,324 | 2005-09-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080043383A true KR20080043383A (ko) | 2008-05-16 |
Family
ID=38309561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087007975A Withdrawn KR20080043383A (ko) | 2005-09-02 | 2006-08-31 | Ｆａｐ 저해제 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8183280B2 (https=) |
| EP (2) | EP1760076A1 (https=) |
| JP (1) | JP2009507011A (https=) |
| KR (1) | KR20080043383A (https=) |
| AU (1) | AU2006336854A1 (https=) |
| CA (1) | CA2627607A1 (https=) |
| NO (1) | NO20081636L (https=) |
| RU (1) | RU2008112683A (https=) |
| WO (1) | WO2007085895A2 (https=) |
| ZA (1) | ZA200802867B (https=) |
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| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| EP2540725A1 (de) | 2006-05-04 | 2013-01-02 | Boehringer Ingelheim International GmbH | Polymorphe von 1-((4-Methyl-chinazolin-2-yl)methyl)-3-methyl-7-(2-butin-1-yl)-8-(3-(R)-amino-piperidin-1-yl)xanthin |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| US8933201B2 (en) | 2006-06-07 | 2015-01-13 | The Board Of Regents Of The University Of Oklahoma | Substrates and inhibitors of antiplasmin cleaving enzyme and fibroblast activation protein and methods of use |
| WO2009024542A2 (en) * | 2007-08-17 | 2009-02-26 | Boehringer Ingelheim International Gmbh | Purin derivatives for use in the treatment of fab-related diseases |
| EP2071337A1 (en) * | 2007-12-10 | 2009-06-17 | F.Hoffmann-La Roche Ag | Seprase as a marker for cancer |
| CN101896818B (zh) * | 2007-12-10 | 2016-01-20 | 霍夫曼-拉罗奇有限公司 | 作为癌症的标记物的Seprase |
| MY155630A (en) * | 2008-03-05 | 2015-11-13 | Nat Health Research Institutes | Pyrrolidine derivatives |
| PE20091730A1 (es) | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| BRPI0916997A2 (pt) | 2008-08-06 | 2020-12-15 | Boehringer Ingelheim International Gmbh | Inibidor de dpp-4 e seu uso |
| CN102149407A (zh) | 2008-09-10 | 2011-08-10 | 贝林格尔.英格海姆国际有限公司 | 治疗糖尿病和相关病症的组合疗法 |
| WO2010036814A1 (en) * | 2008-09-25 | 2010-04-01 | Molecular Insight Pharmaceuticals, Inc. | Selective seprase inhibitors |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
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| AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
| WO2010083570A1 (en) * | 2009-01-23 | 2010-07-29 | The University Of Sydney | Novel metabolic disease therapy |
| KR20240090632A (ko) | 2009-11-27 | 2024-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료 |
| CN102946875A (zh) | 2010-05-05 | 2013-02-27 | 贝林格尔.英格海姆国际有限公司 | 组合疗法 |
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| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| JP6218811B2 (ja) | 2012-05-14 | 2017-10-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｓｉｒｓ及び／又は敗血症の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| JP6224084B2 (ja) | 2012-05-14 | 2017-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
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| EA021236B1 (ru) * | 2012-10-03 | 2015-05-29 | Дафот Энтерпраизес Лимитед | Nα-АЦИЛЬНЫЕ ПРОИЗВОДНЫЕ АМИНОАЦИЛ-2-ЦИАНОПИРРОЛИДИНА - ИНГИБИТОРЫ ПРОЛИЛЭНДОПЕПТИДАЗЫ И ДИПЕПТИДИЛПЕПТИДАЗЫ-IV, ОБЛАДАЮЩИЕ ГИПОГЛИКЕМИЧЕСКИМ, ПРОТИВОГИПОКСИЧЕСКИМ, НЕЙРОПРОТЕКТОРНЫМ И УЛУЧШАЮЩИМ КОГНИТИВНЫЕ ФУНКЦИИ ДЕЙСТВИЕМ |
| EP2730571A1 (en) * | 2012-11-12 | 2014-05-14 | Universitat De Barcelona | 1-[1-(benzoyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile derivatives |
| EP3110449B1 (en) | 2014-02-28 | 2023-06-28 | Boehringer Ingelheim International GmbH | Medical use of a dpp-4 inhibitor |
| AU2015266654A1 (en) * | 2014-05-30 | 2016-12-01 | British Columbia Cancer Agency Branch | Androgen receptor modulators and methods for their use |
| CN109310697A (zh) | 2016-06-10 | 2019-02-05 | 勃林格殷格翰国际有限公司 | 利格列汀和二甲双胍的组合 |
| CN116474108A (zh) | 2016-12-14 | 2023-07-25 | 普渡研究基金会 | 成纤维细胞活化蛋白(fap)-靶向成像和治疗 |
| US11613785B2 (en) | 2017-01-09 | 2023-03-28 | Onkosxcel Therapeutics, Llc | Predictive and diagnostic methods for prostate cancer |
| US11780821B2 (en) | 2017-12-15 | 2023-10-10 | Praxis Biotech LLC | Inhibitors of fibroblast activation protein |
| US11504364B2 (en) | 2018-12-21 | 2022-11-22 | Praxis Biotech LLC | Inhibitors of fibroblast activation protein |
| KR102274077B1 (ko) * | 2019-03-29 | 2021-07-09 | 보령제약 주식회사 | Fap 저해제로서의 피롤리딘 유도체 및 이를 포함하는 약학적 조성물 |
| EP4055014B1 (en) | 2019-11-06 | 2025-04-30 | Yuhan Corporation | PYRROLIDINE AND PIPERIDINE COMPOUNDS |
| EP4126053A4 (en) * | 2020-03-24 | 2024-11-20 | Trustees Of Tufts College | IMAGING AGENTS AND RADIOPHARMACEUTICALS TARGETING FAP, AND USES THEREOF |
| CN115943312A (zh) | 2020-05-07 | 2023-04-07 | 法国居里学院 | 免疫抑制性成纤维细胞群体的生物标志物antxr1及其在预测对免疫疗法的反应中的用途 |
| EP4263535A1 (en) * | 2020-12-17 | 2023-10-25 | Astrazeneca AB | N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)- quinoline-4-carboxamides |
| AU2022306289A1 (en) | 2021-07-09 | 2024-01-18 | Aligos Therapeutics, Inc. | Anti-viral compounds |
| WO2023043816A1 (en) | 2021-09-17 | 2023-03-23 | Aligos Therapeutics, Inc. | Anti-viral compounds for treating coronavirus, picornavirus, and norovirus infections |
| JP2025525344A (ja) * | 2022-06-21 | 2025-08-05 | アストラゼネカ・アクチエボラーグ | Ｎ－（２－（４－シアノチアゾリジン－３－イル）－２－オキソエチル）－キノリン－４－カルボキサミド |
| EP4543869A1 (en) * | 2022-06-21 | 2025-04-30 | Astrazeneca AB | N-(2-(3-cyano-2-azabicyclo[3.1.0]hexan-2-yl)-2-oxoethyl)- quinoline-4-carboxamides |
| IL317722A (en) * | 2022-06-21 | 2025-02-01 | Astrazeneca Ab | Solid state forms of N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide |
| WO2025046043A1 (en) | 2023-08-31 | 2025-03-06 | Stichting Radboud Universitair Medisch Centrum | Endometriosis tracer |
| CN118955616B (zh) * | 2024-05-01 | 2025-09-02 | 杭州景嘉航生物医药科技有限公司 | 一种靶向结合成纤维细胞活化蛋白化合物及应用 |
| WO2026007968A1 (zh) * | 2024-07-01 | 2026-01-08 | 杭州景嘉航生物医药科技有限公司 | 一种靶向结合成纤维细胞活化蛋白的化合物及应用 |
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-
2005
- 2005-09-02 EP EP05108049A patent/EP1760076A1/en not_active Withdrawn
-
2006
- 2006-08-31 EP EP06849433A patent/EP1919864A2/en not_active Withdrawn
- 2006-08-31 US US11/991,286 patent/US8183280B2/en not_active Expired - Fee Related
- 2006-08-31 KR KR1020087007975A patent/KR20080043383A/ko not_active Withdrawn
- 2006-08-31 WO PCT/IB2006/003512 patent/WO2007085895A2/en not_active Ceased
- 2006-08-31 CA CA002627607A patent/CA2627607A1/en not_active Abandoned
- 2006-08-31 RU RU2008112683/04A patent/RU2008112683A/ru not_active Application Discontinuation
- 2006-08-31 AU AU2006336854A patent/AU2006336854A1/en not_active Abandoned
- 2006-08-31 JP JP2008528601A patent/JP2009507011A/ja active Pending
-
2008
- 2008-04-01 ZA ZA200802867A patent/ZA200802867B/xx unknown
- 2008-04-02 NO NO20081636A patent/NO20081636L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1919864A2 (en) | 2008-05-14 |
| WO2007085895A3 (en) | 2008-04-17 |
| US20100081701A1 (en) | 2010-04-01 |
| WO2007085895A2 (en) | 2007-08-02 |
| EP1760076A1 (en) | 2007-03-07 |
| JP2009507011A (ja) | 2009-02-19 |
| AU2006336854A1 (en) | 2007-08-02 |
| ZA200802867B (en) | 2008-12-31 |
| RU2008112683A (ru) | 2009-10-20 |
| CA2627607A1 (en) | 2007-08-02 |
| US8183280B2 (en) | 2012-05-22 |
| NO20081636L (no) | 2008-05-29 |
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