JP2006503057A5 - - Google Patents
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- Publication number
- JP2006503057A5 JP2006503057A5 JP2004537831A JP2004537831A JP2006503057A5 JP 2006503057 A5 JP2006503057 A5 JP 2006503057A5 JP 2004537831 A JP2004537831 A JP 2004537831A JP 2004537831 A JP2004537831 A JP 2004537831A JP 2006503057 A5 JP2006503057 A5 JP 2006503057A5
- Authority
- JP
- Japan
- Prior art keywords
- carbonitrile
- glycyl
- pyrrolidine
- ethynyl
- ethynylpyrrolidine
- 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
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- -1 2-indolinyl Chemical group 0.000 claims 57
- 150000001875 compounds Chemical class 0.000 claims 33
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 31
- 125000000217 alkyl group Chemical group 0.000 claims 27
- 229910052739 hydrogen Inorganic materials 0.000 claims 19
- 239000001257 hydrogen Substances 0.000 claims 19
- ALSCEGDXFJIYES-UHFFFAOYSA-N pyrrolidine-2-carbonitrile Chemical compound N#CC1CCCN1 ALSCEGDXFJIYES-UHFFFAOYSA-N 0.000 claims 19
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims 16
- 125000003342 alkenyl group Chemical group 0.000 claims 15
- 125000000304 alkynyl group Chemical group 0.000 claims 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 12
- 125000000623 heterocyclic group Chemical group 0.000 claims 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims 7
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 5
- 125000005129 aryl carbonyl group Chemical group 0.000 claims 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 3
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 3
- WLGYZHSSENEZRE-AVGNSLFASA-N (2s,5r)-1-[(2s)-2-amino-2-cyclopentylacetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1([C@H](N)C(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCCC1 WLGYZHSSENEZRE-AVGNSLFASA-N 0.000 claims 2
- XXTBOOXAFXMJIZ-SRVKXCTJSA-N (2s,5r)-1-[(2s)-2-amino-4-methylpentanoyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound CC(C)C[C@H](N)C(=O)N1[C@@H](C#C)CC[C@H]1C#N XXTBOOXAFXMJIZ-SRVKXCTJSA-N 0.000 claims 2
- QNJHRRHEUUPUFK-IRDVNMAFSA-N (2s,5r)-5-ethynyl-1-[2-[[1-methyl-4-[5-(trifluoromethyl)pyridin-2-yl]oxycyclohexyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCC1OC1=CC=C(C(F)(F)F)C=N1 QNJHRRHEUUPUFK-IRDVNMAFSA-N 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
- 125000005282 allenyl group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- GWVRCGAFLKJTEN-AIHGNGHHSA-N (2S,5S)-5-methyl-1-[2-[[(1S,5R)-3-tricyclo[3.3.1.03,7]nonanyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@]1(CC2C[C@@](C3)(C1)[H])[H])C23NCC(=O)N1[C@@H](C)CC[C@H]1C#N GWVRCGAFLKJTEN-AIHGNGHHSA-N 0.000 claims 1
- FRGISDJQXAKTDV-MELADBBJSA-N (2s,5r)-1-[(2r)-2-amino-2-cyclohexylacetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1([C@@H](N)C(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCCCC1 FRGISDJQXAKTDV-MELADBBJSA-N 0.000 claims 1
- SOGGVAAJATVSRA-RWMBFGLXSA-N (2s,5r)-1-[(2r)-2-amino-2-cyclopentylacetyl]-5-ethenylpyrrolidine-2-carbonitrile Chemical compound C1([C@@H](N)C(=O)N2[C@@H](CC[C@@H]2C=C)C#N)CCCC1 SOGGVAAJATVSRA-RWMBFGLXSA-N 0.000 claims 1
- ADOYZNNVXXDNOW-IHRRRGAJSA-N (2s,5r)-1-[(2s)-2-amino-2-cyclohexylacetyl]-5-ethenylpyrrolidine-2-carbonitrile Chemical compound C1([C@H](N)C(=O)N2[C@@H](CC[C@@H]2C=C)C#N)CCCCC1 ADOYZNNVXXDNOW-IHRRRGAJSA-N 0.000 claims 1
- FRGISDJQXAKTDV-IHRRRGAJSA-N (2s,5r)-1-[(2s)-2-amino-2-cyclohexylacetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1([C@H](N)C(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCCCC1 FRGISDJQXAKTDV-IHRRRGAJSA-N 0.000 claims 1
- SOGGVAAJATVSRA-AVGNSLFASA-N (2s,5r)-1-[(2s)-2-amino-2-cyclopentylacetyl]-5-ethenylpyrrolidine-2-carbonitrile Chemical compound C1([C@H](N)C(=O)N2[C@@H](CC[C@@H]2C=C)C#N)CCCC1 SOGGVAAJATVSRA-AVGNSLFASA-N 0.000 claims 1
- XMYBPHZGYQEJKQ-XSXXDBAGSA-N (2s,5r)-1-[2-(1-adamantylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1C(C2)CC(C3)CC2CC13NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N XMYBPHZGYQEJKQ-XSXXDBAGSA-N 0.000 claims 1
- CGPXQFKYXWWTLB-RYUDHWBXSA-N (2s,5r)-1-[2-(cyclobutylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CCC1 CGPXQFKYXWWTLB-RYUDHWBXSA-N 0.000 claims 1
- HDKGJFXDNVUINF-GJZGRUSLSA-N (2s,5r)-1-[2-(cycloheptylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CCCCCC1 HDKGJFXDNVUINF-GJZGRUSLSA-N 0.000 claims 1
- GFCJINGFBXPTAG-KBPBESRZSA-N (2s,5r)-1-[2-(cyclohexylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CCCCC1 GFCJINGFBXPTAG-KBPBESRZSA-N 0.000 claims 1
- PAOXGRAINLIPSS-STQMWFEESA-N (2s,5r)-1-[2-(cyclopentylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CCCC1 PAOXGRAINLIPSS-STQMWFEESA-N 0.000 claims 1
- VBQFUZRGSACCBZ-QWRGUYRKSA-N (2s,5r)-1-[2-(cyclopropylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CC1 VBQFUZRGSACCBZ-QWRGUYRKSA-N 0.000 claims 1
- AYFKPVVQCFNFFY-QWRGUYRKSA-N (2s,5r)-1-[2-(tert-butylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound CC(C)(C)NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N AYFKPVVQCFNFFY-QWRGUYRKSA-N 0.000 claims 1
- VSYGRYMDJJHFTC-STQMWFEESA-N (2s,5r)-1-[2-[2-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]ethylamino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound ClC1=CC(C(F)(F)F)=CN=C1NCCNCC(=O)N1[C@H](C#N)CC[C@@H]1C#C VSYGRYMDJJHFTC-STQMWFEESA-N 0.000 claims 1
- ZCBKMVXYSNNRAE-AIEDFZFUSA-N (2s,5r)-1-[2-[[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N([C@H]1[C@]2([H])CC[C@@](C2)(C1)[H])CC(=O)N1[C@@H](C#C)CC[C@H]1C#N ZCBKMVXYSNNRAE-AIEDFZFUSA-N 0.000 claims 1
- ZCBKMVXYSNNRAE-UZSCSNNJSA-N (2s,5r)-1-[2-[[(1s,4r)-3-bicyclo[2.2.1]heptanyl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1([C@]2([H])CC[C@@](C2)(C1)[H])NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N ZCBKMVXYSNNRAE-UZSCSNNJSA-N 0.000 claims 1
- CJLKZSAZEFHUPQ-GJZGRUSLSA-N (2s,5r)-1-[2-[[1-(1,3-benzothiazol-2-ylamino)-2-methylpropan-2-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N=1C2=CC=CC=C2SC=1NCC(C)(C)NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N CJLKZSAZEFHUPQ-GJZGRUSLSA-N 0.000 claims 1
- LXKFPJQGEJYBIP-IRXDYDNUSA-N (2s,5r)-1-[2-[[1-(2-cyano-5-fluorophenoxy)-2-methylpropan-2-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC(C)(C)COC1=CC(F)=CC=C1C#N LXKFPJQGEJYBIP-IRXDYDNUSA-N 0.000 claims 1
- ZTYLMFRQXAVJLT-ICSRJNTNSA-N (2s,5r)-1-[2-[[1-(3-cyanophenyl)-4-methylpiperidin-4-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCN1C1=CC=CC(C#N)=C1 ZTYLMFRQXAVJLT-ICSRJNTNSA-N 0.000 claims 1
- AOBLBPOOAASJAY-OALUTQOASA-N (2s,5r)-1-[2-[[1-(4-bromobenzoyl)-4-methylpiperidin-4-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCN1C(=O)C1=CC=C(Br)C=C1 AOBLBPOOAASJAY-OALUTQOASA-N 0.000 claims 1
- WCQXAVDREAIDAV-OALUTQOASA-N (2s,5r)-1-[2-[[1-(4-chlorobenzoyl)-4-methylpiperidin-4-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCN1C(=O)C1=CC=C(Cl)C=C1 WCQXAVDREAIDAV-OALUTQOASA-N 0.000 claims 1
- LFRXAAGPLSHLOR-OALUTQOASA-N (2s,5r)-1-[2-[[1-(4-chlorobenzoyl)piperidin-4-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CC1 LFRXAAGPLSHLOR-OALUTQOASA-N 0.000 claims 1
- PEAHDBDUWWSDHW-PMACEKPBSA-N (2s,5r)-1-[2-[[1-(4-cyanobenzoyl)-4-methylpiperidin-4-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCN1C(=O)C1=CC=C(C#N)C=C1 PEAHDBDUWWSDHW-PMACEKPBSA-N 0.000 claims 1
- VLAPRGLPYLXNQC-IRXDYDNUSA-N (2s,5r)-1-[2-[[1-(5-chloropyridin-2-yl)-4-methylpiperidin-4-yl]amino]acetyl]-5-ethynylpyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCN1C1=CC=C(Cl)C=N1 VLAPRGLPYLXNQC-IRXDYDNUSA-N 0.000 claims 1
- OUKUHZKNGLRGRJ-JYJNAYRXSA-N (2s,5r)-5-ethynyl-1-[(3s)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]pyrrolidine-2-carbonitrile Chemical compound O=C([C@H]1NCC2=CC=CC=C2C1)N1[C@@H](C#C)CC[C@H]1C#N OUKUHZKNGLRGRJ-JYJNAYRXSA-N 0.000 claims 1
- NAMRVSAUNWIJNM-KBPBESRZSA-N (2s,5r)-5-ethynyl-1-[2-(2,4,4-trimethylpentan-2-ylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound CC(C)(C)CC(C)(C)NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N NAMRVSAUNWIJNM-KBPBESRZSA-N 0.000 claims 1
- NRGHIGFZYSBLQJ-RYUDHWBXSA-N (2s,5r)-5-ethynyl-1-[2-(2-methylbutan-2-ylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound CCC(C)(C)NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N NRGHIGFZYSBLQJ-RYUDHWBXSA-N 0.000 claims 1
- ABHKYJSXPJZTAN-GJZGRUSLSA-N (2s,5r)-5-ethynyl-1-[2-(2-pyridin-4-ylethylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNCCC1=CC=NC=C1 ABHKYJSXPJZTAN-GJZGRUSLSA-N 0.000 claims 1
- ZUMRJPNZDXLRTC-KBPBESRZSA-N (2s,5r)-5-ethynyl-1-[2-(3-propan-2-yloxypropylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound CC(C)OCCCNCC(=O)N1[C@@H](C#C)CC[C@H]1C#N ZUMRJPNZDXLRTC-KBPBESRZSA-N 0.000 claims 1
- UIMBZPRWYBAKNN-STQMWFEESA-N (2s,5r)-5-ethynyl-1-[2-(oxan-4-ylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CCOCC1 UIMBZPRWYBAKNN-STQMWFEESA-N 0.000 claims 1
- OJZREVAFYSJEBS-VYAYZGMFSA-N (2s,5r)-5-ethynyl-1-[2-(oxolan-2-ylmethylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNCC1CCCO1 OJZREVAFYSJEBS-VYAYZGMFSA-N 0.000 claims 1
- YPKDEDQORSVCBF-RAMGSTBQSA-N (2s,5r)-5-ethynyl-1-[2-(oxolan-3-ylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CCOC1 YPKDEDQORSVCBF-RAMGSTBQSA-N 0.000 claims 1
- JCONWQPPNCIKSH-STQMWFEESA-N (2s,5r)-5-ethynyl-1-[2-(piperidin-4-ylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1CCNCC1 JCONWQPPNCIKSH-STQMWFEESA-N 0.000 claims 1
- FGPHPVZAMFRKCX-KBPBESRZSA-N (2s,5r)-5-ethynyl-1-[2-(pyridin-2-ylmethylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNCC1=CC=CC=N1 FGPHPVZAMFRKCX-KBPBESRZSA-N 0.000 claims 1
- AVEDBIVZROIHRS-IRXDYDNUSA-N (2s,5r)-5-ethynyl-1-[2-[(1-pyridin-2-ylpiperidin-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC(CC1)CCN1C1=CC=CC=N1 AVEDBIVZROIHRS-IRXDYDNUSA-N 0.000 claims 1
- UALCSJKCLSEBIH-RYUDHWBXSA-N (2s,5r)-5-ethynyl-1-[2-[(3-hydroxy-2,2-dimethylpropyl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound OCC(C)(C)CNCC(=O)N1[C@@H](C#C)CC[C@H]1C#N UALCSJKCLSEBIH-RYUDHWBXSA-N 0.000 claims 1
- RJSJVYMTPHMGGA-ILGZHXLLSA-N (2s,5r)-5-ethynyl-1-[2-[(4-hydroxy-1-methylcyclohexyl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1(C)CCC(O)CC1 RJSJVYMTPHMGGA-ILGZHXLLSA-N 0.000 claims 1
- FPGIYBPNQHUTFG-GJZGRUSLSA-N (2s,5r)-5-ethynyl-1-[2-[(4-iodophenyl)methylamino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1=CC(I)=CC=C1CNCC(=O)N1[C@H](C#N)CC[C@@H]1C#C FPGIYBPNQHUTFG-GJZGRUSLSA-N 0.000 claims 1
- ZULCHIGDLPHEPE-IRXDYDNUSA-N (2s,5r)-5-ethynyl-1-[2-[(4-methyl-1-pyridin-2-ylpiperidin-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCN1C1=CC=CC=N1 ZULCHIGDLPHEPE-IRXDYDNUSA-N 0.000 claims 1
- RJLGUOCTDWCYPO-RYUDHWBXSA-N (2s,5r)-5-ethynyl-1-[2-[3-(methylamino)propylamino]acetyl]pyrrolidine-2-carbonitrile Chemical compound CNCCCNCC(=O)N1[C@@H](C#C)CC[C@H]1C#N RJLGUOCTDWCYPO-RYUDHWBXSA-N 0.000 claims 1
- MHILRUWSMSXEGC-XYIZDEMUSA-N (2s,5r)-5-ethynyl-1-[2-[[(2s)-2-hydroxycyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound O[C@H]1CCCC1NCC(=O)N1[C@H](C#N)CC[C@@H]1C#C MHILRUWSMSXEGC-XYIZDEMUSA-N 0.000 claims 1
- FLEJLFCEMOMGJU-KGVIZRLGSA-N (2s,5r)-5-ethynyl-1-[2-[[(5r,7s)-3-hydroxy-1-adamantyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@@](C1)([H])C[C@@](C2)(C3)[H])C2(O)CC31NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N FLEJLFCEMOMGJU-KGVIZRLGSA-N 0.000 claims 1
- UWQNMCCYXHILOT-KBPBESRZSA-N (2s,5r)-5-ethynyl-1-[2-[[1-(2-hydroxypropan-2-yl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1(C(C)(O)C)CCCC1 UWQNMCCYXHILOT-KBPBESRZSA-N 0.000 claims 1
- PZHXBQYIQQDZNF-IRXDYDNUSA-N (2s,5r)-5-ethynyl-1-[2-[[1-(4-fluorophenyl)-2-methylpropan-2-yl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC(C)(C)CC1=CC=C(F)C=C1 PZHXBQYIQQDZNF-IRXDYDNUSA-N 0.000 claims 1
- JKHALJALYGUOKY-STQMWFEESA-N (2s,5r)-5-ethynyl-1-[2-[[1-(hydroxymethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1(CO)CCCC1 JKHALJALYGUOKY-STQMWFEESA-N 0.000 claims 1
- DOOWKXARHBIBJS-KBPBESRZSA-N (2s,5r)-5-ethynyl-1-[2-[[1-(methoxymethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC1(COC)CCCC1 DOOWKXARHBIBJS-KBPBESRZSA-N 0.000 claims 1
- UCOZFJBTDHDXCE-IRXDYDNUSA-N (2s,5r)-5-ethynyl-1-[2-[[2-methyl-1-(quinolin-4-ylamino)propan-2-yl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C=1C=NC2=CC=CC=C2C=1NCC(C)(C)NCC(=O)N1[C@@H](C#C)CC[C@H]1C#N UCOZFJBTDHDXCE-IRXDYDNUSA-N 0.000 claims 1
- ITBDHPHHCXVSCN-GJZGRUSLSA-N (2s,5r)-5-ethynyl-1-[2-[[2-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]oxypropan-2-yl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC(C)(C)COC1=CC=C(C(F)(F)F)C=N1 ITBDHPHHCXVSCN-GJZGRUSLSA-N 0.000 claims 1
- ZOPXQJZSDLRPKC-STQMWFEESA-N (2s,5r)-5-ethynyl-1-[2-[[2-methyl-1-[[4-(trifluoromethyl)pyrimidin-2-yl]amino]propan-2-yl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC[C@@H]1C#C)C#N)C(=O)CNC(C)(C)CNC1=NC=CC(C(F)(F)F)=N1 ZOPXQJZSDLRPKC-STQMWFEESA-N 0.000 claims 1
- QOZWNOXVGRAMJD-BXRCABCMSA-N (2s,5r)-5-ethynyl-1-[2-[[4-(3-fluorophenoxy)-1-methylcyclohexyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](CC[C@@H]2C#C)C#N)CCC1OC1=CC=CC(F)=C1 QOZWNOXVGRAMJD-BXRCABCMSA-N 0.000 claims 1
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24683102A | 2002-09-19 | 2002-09-19 | |
| US10/246,831 | 2002-09-19 | ||
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| PCT/US2003/029018 WO2004026822A2 (en) | 2002-09-19 | 2003-09-15 | Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-iv (dpp-iv) |
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| US7205409B2 (en) | 2003-09-04 | 2007-04-17 | Abbott Laboratories | Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV) |
| WO2005023762A1 (en) * | 2003-09-04 | 2005-03-17 | Abbott Laboratories | Pyrrolidine-2-carbonitrile derivatives and their use as inhibitors of dipeptidyl peptidase-iv (dpp-iv) |
| WO2005073186A1 (ja) * | 2004-01-29 | 2005-08-11 | Ono Pharmaceutical Co., Ltd. | ピロリジン誘導体 |
| CN101684089A (zh) | 2004-02-05 | 2010-03-31 | 杏林制药株式会社 | 双环酯类衍生物 |
| WO2005095339A1 (en) * | 2004-03-31 | 2005-10-13 | Pfizer Products Inc. | Dicyanopyrrolidines as dipeptidyl peptidase iv inhibitors |
| CA2564884A1 (en) * | 2004-05-18 | 2005-12-08 | Merck & Co., Inc. | Cyclohexylalanine derivatives as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
| MXPA06015169A (es) * | 2004-07-08 | 2007-08-21 | Warner Lambert Co | Moduladores de androgenos. |
| WO2006011035A1 (en) * | 2004-07-23 | 2006-02-02 | Glenmark Pharmaceuticals Ltd. | Novel dipeptidyl peptidase iv inhibitors; process for their preparation and compositions containing them |
| AU2005267093B2 (en) * | 2004-07-23 | 2009-10-01 | Nuada Llc | Peptidase inhibitors |
| NZ554515A (en) | 2004-10-12 | 2009-12-24 | Glenmark Pharmaceuticals Sa | Novel dipeptidyl peptidase IV inhibitors, pharmaceutical compositions containing them, and process for their preparation |
| JP2008019168A (ja) * | 2004-10-22 | 2008-01-31 | Astellas Pharma Inc | ２−シアノ−４−フルオロピロリジン誘導体の製造法 |
| WO2006118196A1 (ja) * | 2005-04-27 | 2006-11-09 | Ajinomoto Co., Inc. | Dpp4阻害剤及びその医薬用途 |
| US20080300251A1 (en) * | 2005-09-05 | 2008-12-04 | Sattigeri Jitendra A | Derivatives of 3-Azabicyclo[3.1.0] Hexane as Dipeptidyl Peptidase-IV Inhibitors |
| SI1942898T2 (sl) | 2005-09-14 | 2014-08-29 | Takeda Pharmaceutical Company Limited | Dipeptidil-peptidazni inhibitorji za zdravljenje diabetesa |
| EP1924567B1 (en) | 2005-09-16 | 2012-08-22 | Takeda Pharmaceutical Company Limited | Process for the preparation of pyrimidinedione derivatives |
| GB0526291D0 (en) | 2005-12-23 | 2006-02-01 | Prosidion Ltd | Therapeutic method |
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| WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP2004601B1 (en) * | 2006-04-03 | 2011-03-02 | Matrix Laboratories Limited | Novel dipeptidyl peptidase iv inhibitors and processes for their preparation and pharmaceutical compositions containing them |
| AU2007235876A1 (en) | 2006-04-12 | 2007-10-18 | Probiodrug Ag | Enzyme inhibitors |
| US9260411B2 (en) * | 2006-07-20 | 2016-02-16 | Abbvie Inc. | Synthesis of (2S,5R)-5-ethynyl-1-{N-(4-methyl-1-(4-carboxy-pyridin-2-yl)piperidin-4-yl)glycyl}pyrrolidine-2-carbonitrile |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| EP2091948B1 (en) | 2006-11-30 | 2012-04-18 | Probiodrug AG | Novel inhibitors of glutaminyl cyclase |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| EP2123636B1 (en) | 2007-03-22 | 2012-03-21 | Kyorin Pharmaceutical Co., Ltd. | Method for producing aminoacetylpyrrolidinecarbonitrile derivative |
| US9656991B2 (en) | 2007-04-18 | 2017-05-23 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| GB2465132B (en) | 2007-09-21 | 2012-06-06 | Lupin Ltd | Compounds as dipeptidyl peptidase IV (DPP IV) inhibitors |
| WO2010016584A1 (ja) | 2008-08-07 | 2010-02-11 | 杏林製薬株式会社 | ビシクロ[２．２．２]オクチルアミン誘導体の製造方法 |
| US8748457B2 (en) | 2009-06-18 | 2014-06-10 | Lupin Limited | 2-amino-2- [8-(dimethyl carbamoyl)- 8-aza- bicyclo [3.2.1] oct-3-yl]-exo- ethanoyl derivatives as potent DPP-IV inhibitors |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| ES2548913T3 (es) | 2009-09-11 | 2015-10-21 | Probiodrug Ag | Derivados heterocíclicos como inhibidores de glutaminil ciclasa |
| WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
| CA2789440C (en) | 2010-03-10 | 2020-03-24 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
| JP5764148B2 (ja) * | 2010-03-10 | 2015-08-12 | ヤンセン ファーマシューティカ エヌ．ベー． | ジペプチジルペプチダーゼ−１（ｄｐｐ−１）の阻害剤として有用な４，４−二置換されたピペリジン誘導体 |
| WO2011127051A1 (en) | 2010-04-06 | 2011-10-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| JP5945532B2 (ja) | 2010-04-21 | 2016-07-05 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤としてのベンゾイミダゾール誘導体 |
| TWI403716B (zh) * | 2010-08-13 | 2013-08-01 | Nat Univ Tsing Hua | 氫氣檢測器、系統及方法 |
| MX2013003184A (es) | 2010-09-22 | 2013-06-07 | Arena Pharm Inc | Moduladores del receptor gpr119 y el tratamiento de transtornos relacionados con el mismo. |
| US8530670B2 (en) | 2011-03-16 | 2013-09-10 | Probiodrug Ag | Inhibitors |
| WO2012135570A1 (en) | 2011-04-01 | 2012-10-04 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2012145361A1 (en) | 2011-04-19 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2012145603A1 (en) | 2011-04-22 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US20140051714A1 (en) | 2011-04-22 | 2014-02-20 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| TWI500613B (zh) | 2012-10-17 | 2015-09-21 | Cadila Healthcare Ltd | 新穎之雜環化合物 |
| WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
| CN105601584A (zh) * | 2013-01-06 | 2016-05-25 | 天津市汉康医药生物技术有限公司 | 噻唑烷衍生物、其制备方法和用途 |
| JP6590226B2 (ja) * | 2016-05-11 | 2019-10-16 | 株式会社シード探索研究所 | オキサアジリジン化合物およびその製造方法 |
| US11096924B2 (en) | 2016-09-07 | 2021-08-24 | Trustees Of Tufts College | Combination therapies using immuno-dash inhibitors and PGE2 antagonists |
| EP3461819B1 (en) | 2017-09-29 | 2020-05-27 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
| CN114213504B (zh) * | 2021-12-24 | 2023-05-09 | 西南医科大学 | 一类具有抗糖尿病活性的化合物及其应用 |
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| FR2678938B1 (fr) * | 1991-07-10 | 1993-10-08 | Rhone Poulenc Rorer Sa | Derives de pyrrolidine, leur preparation et les medicaments les contenant. |
| US5691356A (en) * | 1994-03-21 | 1997-11-25 | Bristol-Myers Squibb Company | Disubstituted heterocyclic thrombin inhibitors |
| CO5150173A1 (es) * | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
| US6172081B1 (en) | 1999-06-24 | 2001-01-09 | Novartis Ag | Tetrahydroisoquinoline 3-carboxamide derivatives |
| TW583185B (en) * | 2000-06-13 | 2004-04-11 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines and pharmaceutical composition for inhibiting dipeptidyl peptidase-IV (DPP-IV) or for the prevention or treatment of diseases or conditions associated with elevated levels of DPP-IV comprising the same |
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- 2003-09-15 JP JP2004537831A patent/JP4712387B2/ja not_active Expired - Fee Related
- 2003-09-15 CA CA2768674A patent/CA2768674A1/en not_active Abandoned
- 2003-09-15 PT PT03774478T patent/PT1560811E/pt unknown
- 2003-09-15 DK DK03774478T patent/DK1560811T3/da active
- 2003-09-15 AU AU2003282800A patent/AU2003282800B2/en not_active Ceased
- 2003-09-15 NZ NZ538567A patent/NZ538567A/en not_active IP Right Cessation
- 2003-09-15 BR BR0314582-4A patent/BR0314582A/pt not_active IP Right Cessation
- 2003-09-15 KR KR1020057004773A patent/KR101072236B1/ko not_active Expired - Fee Related
- 2003-09-15 PL PL03374732A patent/PL374732A1/xx unknown
- 2003-09-15 AT AT03774478T patent/ATE368647T1/de active
- 2003-09-15 ES ES03774478T patent/ES2290511T3/es not_active Expired - Lifetime
- 2003-09-15 DE DE60315336T patent/DE60315336T2/de not_active Expired - Lifetime
- 2003-09-15 MX MXPA05003091A patent/MXPA05003091A/es active IP Right Grant
- 2003-09-15 EP EP03774478A patent/EP1560811B9/en not_active Expired - Lifetime
- 2003-09-15 CN CN200910166852A patent/CN101676264A/zh active Pending
- 2003-09-15 WO PCT/US2003/029018 patent/WO2004026822A2/en not_active Ceased
- 2003-09-19 TW TW092125921A patent/TWI320406B/zh not_active IP Right Cessation
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2005
- 2005-02-16 ZA ZA2005/02218A patent/ZA200502218B/en unknown
- 2005-03-15 IL IL167434A patent/IL167434A/en not_active IP Right Cessation
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2007
- 2007-10-23 CY CY20071101364T patent/CY1110361T1/el unknown
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