SK13632002A3 - C1-6-alkyl-4-amino-azepán-3-ónové zlúčeniny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom, ich použitie a medziprodukty - Google Patents
C1-6-alkyl-4-amino-azepán-3-ónové zlúčeniny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom, ich použitie a medziprodukty Download PDFInfo
- Publication number
- SK13632002A3 SK13632002A3 SK1363-2002A SK13632002A SK13632002A3 SK 13632002 A3 SK13632002 A3 SK 13632002A3 SK 13632002 A SK13632002 A SK 13632002A SK 13632002 A3 SK13632002 A3 SK 13632002A3
- Authority
- SK
- Slovakia
- Prior art keywords
- methyl
- alkyl
- azepan
- carboxylic acid
- amide
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 88
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims description 63
- 230000008569 process Effects 0.000 title claims description 8
- 239000000543 intermediate Substances 0.000 title abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 224
- 201000010099 disease Diseases 0.000 claims abstract description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 46
- 108090000625 Cathepsin K Proteins 0.000 claims abstract description 26
- 239000004365 Protease Substances 0.000 claims abstract description 21
- 102000035195 Peptidases Human genes 0.000 claims abstract description 20
- 108091005804 Peptidases Proteins 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 201000004792 malaria Diseases 0.000 claims abstract description 12
- 206010065687 Bone loss Diseases 0.000 claims abstract description 10
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 10
- 239000011159 matrix material Substances 0.000 claims abstract description 10
- 210000000845 cartilage Anatomy 0.000 claims abstract description 9
- 208000007565 gingivitis Diseases 0.000 claims abstract description 8
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 7
- 150000004677 hydrates Chemical class 0.000 claims abstract description 6
- 201000001245 periodontitis Diseases 0.000 claims abstract description 6
- 239000012453 solvate Substances 0.000 claims abstract description 6
- 208000030852 Parasitic disease Diseases 0.000 claims abstract description 5
- 230000015556 catabolic process Effects 0.000 claims abstract 4
- 238000006731 degradation reaction Methods 0.000 claims abstract 4
- 102000004171 Cathepsin K Human genes 0.000 claims abstract 3
- -1 2-methanesulfinyl-ethyl Chemical group 0.000 claims description 521
- 125000000217 alkyl group Chemical group 0.000 claims description 385
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 claims description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 64
- 229910052799 carbon Inorganic materials 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 58
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- 102000005927 Cysteine Proteases Human genes 0.000 claims description 47
- 108010005843 Cysteine Proteases Proteins 0.000 claims description 47
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 21
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 19
- 125000005605 benzo group Chemical class 0.000 claims description 18
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 17
- 125000005425 toluyl group Chemical group 0.000 claims description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 15
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000002541 furyl group Chemical group 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 14
- 125000001972 isopentyl group Chemical class [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- CNUBKCREEQZXNE-UHFFFAOYSA-N 3-methylfuro[3,2-b]pyridine-2-carboxylic acid Chemical compound C1=CN=C2C(C)=C(C(O)=O)OC2=C1 CNUBKCREEQZXNE-UHFFFAOYSA-N 0.000 claims description 13
- VREBIURYOUWZMM-UHFFFAOYSA-N benzyl 2-methyl-2,3,4,7-tetrahydroazepine-1-carboxylate Chemical compound CC1CCC=CCN1C(=O)OCC1=CC=CC=C1 VREBIURYOUWZMM-UHFFFAOYSA-N 0.000 claims description 13
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 13
- 150000004702 methyl esters Chemical class 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 102000012479 Serine Proteases Human genes 0.000 claims description 10
- 108010022999 Serine Proteases Proteins 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 239000007800 oxidant agent Substances 0.000 claims description 10
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 claims description 10
- MYDSAMPAYOLUMG-UHFFFAOYSA-N 3-aminothieno[3,2-b]pyridine-2-carboxylic acid Chemical compound C1=CN=C2C(N)=C(C(O)=O)SC2=C1 MYDSAMPAYOLUMG-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- POVDISSTLXBPFJ-GBAJDQEWSA-N benzyl (2r,5s,6s)-6-hydroxy-2-methyl-5-[[(2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]azepane-1-carboxylate Chemical compound C1[C@H](O)[C@@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC[C@@H](C)N1C(=O)OCC1=CC=CC=C1 POVDISSTLXBPFJ-GBAJDQEWSA-N 0.000 claims description 9
- UDCBOIZIOVLMBA-GFCCVEGCSA-N benzyl n-[(2r)-hex-5-en-2-yl]carbamate Chemical compound C=CCC[C@@H](C)NC(=O)OCC1=CC=CC=C1 UDCBOIZIOVLMBA-GFCCVEGCSA-N 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical class 0.000 claims description 9
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 9
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 9
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 8
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 8
- YMZTUCZCQMQFMK-UHFFFAOYSA-N 3-methyl-1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2C(C)=C(C(O)=O)OC2=C1 YMZTUCZCQMQFMK-UHFFFAOYSA-N 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- DGEXKPJDVGYJKO-BNOWGMLFSA-N benzyl (1r,4r,7s)-4-methyl-8-oxa-5-azabicyclo[5.1.0]octane-5-carboxylate Chemical compound C([C@@H]1O[C@@H]1CC[C@H]1C)N1C(=O)OCC1=CC=CC=C1 DGEXKPJDVGYJKO-BNOWGMLFSA-N 0.000 claims description 8
- BOHJFEPUSOTHGO-XBFCOCLRSA-N benzyl (2r,5s,6s)-5-azido-6-hydroxy-2-methylazepane-1-carboxylate Chemical compound C[C@@H]1CC[C@H](N=[N+]=[N-])[C@@H](O)CN1C(=O)OCC1=CC=CC=C1 BOHJFEPUSOTHGO-XBFCOCLRSA-N 0.000 claims description 8
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 claims description 8
- OQWVUMWJGRYYAO-ILXRZTDVSA-N (2S)-2-amino-4-methyl-N-[(4S,7R)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]pentanamide Chemical compound C1C(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC[C@@H](C)N1S(=O)(=O)C1=CC=CC=N1 OQWVUMWJGRYYAO-ILXRZTDVSA-N 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- 241000243985 Onchocerca volvulus Species 0.000 claims description 7
- 241000223109 Trypanosoma cruzi Species 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- FGKJLKRYENPLQH-UHFFFAOYSA-N isocaproic acid Chemical compound CC(C)CCC(O)=O FGKJLKRYENPLQH-UHFFFAOYSA-N 0.000 claims description 7
- 241000222705 Leishmania pifanoi Species 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- CJKVNTNBIZCKJD-XBFCOCLRSA-N benzyl (2r,5s,6s)-5-amino-6-hydroxy-2-methylazepane-1-carboxylate Chemical compound C[C@@H]1CC[C@H](N)[C@@H](O)CN1C(=O)OCC1=CC=CC=C1 CJKVNTNBIZCKJD-XBFCOCLRSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- PAUKBYFOOOCXCP-UHFFFAOYSA-N benzyl n-hex-5-en-2-yl-n-prop-2-enylcarbamate Chemical compound C=CCCC(C)N(CC=C)C(=O)OCC1=CC=CC=C1 PAUKBYFOOOCXCP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- VHRCHODSRLMXFM-UHFFFAOYSA-N furo[3,2-b]pyridine-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=N1 VHRCHODSRLMXFM-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- JNMCOUZTZNWVRG-QPSCCSFWSA-N tert-butyl n-[(2s)-1-[[(3s,4s,7r)-3-hydroxy-7-methylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CC[C@@H](C)NC[C@@H]1O JNMCOUZTZNWVRG-QPSCCSFWSA-N 0.000 claims description 6
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
- 241000244206 Nematoda Species 0.000 claims description 5
- 125000003236 benzoyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
- 201000004409 schistosomiasis Diseases 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 239000003981 vehicle Substances 0.000 claims description 5
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- HMLVZLLDKBQVFU-UHFFFAOYSA-N 3-methyl-1-pyridin-2-ylsulfonyl-2,3,4,7-tetrahydroazepine Chemical compound C1C(C)CC=CCN1S(=O)(=O)C1=CC=CC=N1 HMLVZLLDKBQVFU-UHFFFAOYSA-N 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 4
- 208000000230 African Trypanosomiasis Diseases 0.000 claims description 4
- 206010001935 American trypanosomiasis Diseases 0.000 claims description 4
- 241000243982 Brugia pahangi Species 0.000 claims description 4
- 208000024699 Chagas disease Diseases 0.000 claims description 4
- 241000224432 Entamoeba histolytica Species 0.000 claims description 4
- 241000242711 Fasciola hepatica Species 0.000 claims description 4
- 241000224466 Giardia Species 0.000 claims description 4
- 241000243974 Haemonchus contortus Species 0.000 claims description 4
- 241001245510 Lambia <signal fly> Species 0.000 claims description 4
- 241000222734 Leishmania mexicana Species 0.000 claims description 4
- 241000203992 Spirometra Species 0.000 claims description 4
- 241000223105 Trypanosoma brucei Species 0.000 claims description 4
- CJKVNTNBIZCKJD-UHFFFAOYSA-N benzyl 5-amino-6-hydroxy-2-methylazepane-1-carboxylate Chemical compound CC1CCC(N)C(O)CN1C(=O)OCC1=CC=CC=C1 CJKVNTNBIZCKJD-UHFFFAOYSA-N 0.000 claims description 4
- BOHJFEPUSOTHGO-UHFFFAOYSA-N benzyl 5-azido-6-hydroxy-2-methylazepane-1-carboxylate Chemical compound CC1CCC(N=[N+]=[N-])C(O)CN1C(=O)OCC1=CC=CC=C1 BOHJFEPUSOTHGO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229940007078 entamoeba histolytica Drugs 0.000 claims description 4
- 108010007459 falcipain Proteins 0.000 claims description 4
- 208000029080 human African trypanosomiasis Diseases 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 4
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 4
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 4
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 4
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 4
- 208000003177 ocular onchocerciasis Diseases 0.000 claims description 4
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 4
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 claims description 4
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 4
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 201000002612 sleeping sickness Diseases 0.000 claims description 4
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- LXOHISCRPIDIIG-UHFFFAOYSA-N 1,4-dioxine-2-carboxylic acid Chemical compound OC(=O)C1=COC=CO1 LXOHISCRPIDIIG-UHFFFAOYSA-N 0.000 claims description 3
- ZRXHLJNBNWVNIM-UHFFFAOYSA-N 3-methyl-1-benzofuran Chemical compound C1=CC=C2C(C)=COC2=C1 ZRXHLJNBNWVNIM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- VIMGDNCXJJETFK-UHFFFAOYSA-N 4-azido-5-methyl-1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound C1C(O)C(N=[N+]=[N-])C(C)CCN1S(=O)(=O)C1=CC=CC=N1 VIMGDNCXJJETFK-UHFFFAOYSA-N 0.000 claims description 3
- HITUZQPFDWNUHA-UHFFFAOYSA-N 5-fluoro-1-benzofuran-2-carboxylic acid Chemical compound FC1=CC=C2OC(C(=O)O)=CC2=C1 HITUZQPFDWNUHA-UHFFFAOYSA-N 0.000 claims description 3
- 208000004554 Leishmaniasis Diseases 0.000 claims description 3
- 241000223960 Plasmodium falciparum Species 0.000 claims description 3
- 241000242680 Schistosoma mansoni Species 0.000 claims description 3
- 241000243774 Trichinella Species 0.000 claims description 3
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N Valeric acid Natural products CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 3
- IGEBYMPQDUNVAF-HZEGPAAWSA-N n-[(2s)-3-cyclohexyl-1-[[(3s,4s,7r)-3-hydroxy-7-methyl-1-propylazepan-4-yl]amino]-1-oxopropan-2-yl]furan-2-carboxamide Chemical compound C1C[C@@H](C)N(CCC)C[C@H](O)[C@H]1NC(=O)[C@@H](NC(=O)C=1OC=CC=1)CC1CCCCC1 IGEBYMPQDUNVAF-HZEGPAAWSA-N 0.000 claims description 3
- JXHNSRQLBAFBHR-HOJAQTOUSA-N n-[(2s)-3-cyclohexyl-1-[[(4s,7r)-7-methyl-3-oxo-1-propylazepan-4-yl]amino]-1-oxopropan-2-yl]furan-2-carboxamide Chemical compound C1C[C@@H](C)N(CCC)CC(=O)[C@H]1NC(=O)[C@@H](NC(=O)C=1OC=CC=1)CC1CCCCC1 JXHNSRQLBAFBHR-HOJAQTOUSA-N 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- ODHZURYHOKTGAY-VVXOGMOBSA-N tert-butyl n-[(2s)-1-[(3-hydroxy-6-methyl-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC(C)CN1S(=O)(=O)C1=CC=CC=N1 ODHZURYHOKTGAY-VVXOGMOBSA-N 0.000 claims description 3
- PJGONEXTSXVJPE-HZEGPAAWSA-N tert-butyl n-[(2s)-1-[[(3s,4s,7r)-1-(benzenesulfonyl)-3-hydroxy-7-methylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1[C@H](O)[C@@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC[C@@H](C)N1S(=O)(=O)C1=CC=CC=C1 PJGONEXTSXVJPE-HZEGPAAWSA-N 0.000 claims description 3
- 201000002311 trypanosomiasis Diseases 0.000 claims description 3
- IKWRSCFUZLOVCC-QXSJWSMHSA-N (2S)-2-amino-N-[(3S,4R,6R)-3-hydroxy-6-methyl-1-pyridin-2-ylsulfonylazepan-4-yl]-4-methylpentanamide Chemical compound C1[C@H](O)[C@H](NC(=O)[C@@H](N)CC(C)C)C[C@@H](C)CN1S(=O)(=O)C1=CC=CC=N1 IKWRSCFUZLOVCC-QXSJWSMHSA-N 0.000 claims description 2
- GLWZXDWTTAOTPH-VOAKCMCISA-N (2S)-2-amino-N-[(3S,4S,7R)-3-hydroxy-7-methyl-1-methylsulfonylazepan-4-yl]-4-methylpentanamide Chemical compound CC(C)C[C@H](N)C(=O)N[C@H]1CC[C@@H](C)N(S(C)(=O)=O)C[C@@H]1O GLWZXDWTTAOTPH-VOAKCMCISA-N 0.000 claims description 2
- 241000244186 Ascaris Species 0.000 claims description 2
- 241000224436 Naegleria Species 0.000 claims description 2
- 241000498271 Necator Species 0.000 claims description 2
- POVDISSTLXBPFJ-JWYYUFOWSA-N benzyl (2r,5s)-6-hydroxy-2-methyl-5-[[(2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]azepane-1-carboxylate Chemical compound C1C(O)[C@@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC[C@@H](C)N1C(=O)OCC1=CC=CC=C1 POVDISSTLXBPFJ-JWYYUFOWSA-N 0.000 claims description 2
- DGEXKPJDVGYJKO-UHFFFAOYSA-N benzyl 4-methyl-8-oxa-5-azabicyclo[5.1.0]octane-5-carboxylate Chemical compound CC1CCC2OC2CN1C(=O)OCC1=CC=CC=C1 DGEXKPJDVGYJKO-UHFFFAOYSA-N 0.000 claims description 2
- BZXUYHZBHCBSNU-KJYDKAEJSA-N n-[(2s)-1-[(3-hydroxy-6-methyl-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-5-methoxy-1-benzofuran-2-carboxamide Chemical compound O=C([C@H](CC(C)C)NC(=O)C=1OC2=CC=C(C=C2C=1)OC)NC(C(C1)O)CC(C)CN1S(=O)(=O)C1=CC=CC=N1 BZXUYHZBHCBSNU-KJYDKAEJSA-N 0.000 claims description 2
- RIBLUARFWJLRNJ-DLTYFMDKSA-N n-[(2s)-3-cyclohexyl-1-[[(3s,4s,7r)-3-hydroxy-7-methyl-1-propylazepan-4-yl]amino]-1-oxopropan-2-yl]-1-benzofuran-2-carboxamide Chemical compound C1C[C@@H](C)N(CCC)C[C@H](O)[C@H]1NC(=O)[C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC1CCCCC1 RIBLUARFWJLRNJ-DLTYFMDKSA-N 0.000 claims description 2
- XBBJFQFWHWGREC-MNAPGUCWSA-N n-[(2s)-3-cyclohexyl-1-[[(3s,4s,7r)-3-hydroxy-7-methyl-1-propylazepan-4-yl]amino]-1-oxopropan-2-yl]thiophene-3-carboxamide Chemical compound C1C[C@@H](C)N(CCC)C[C@H](O)[C@H]1NC(=O)[C@@H](NC(=O)C1=CSC=C1)CC1CCCCC1 XBBJFQFWHWGREC-MNAPGUCWSA-N 0.000 claims description 2
- IWXKVAKADOQHIQ-QMMLZNLJSA-N n-[(2s)-3-cyclohexyl-1-[[(4s,7r)-7-methyl-3-oxo-1-propylazepan-4-yl]amino]-1-oxopropan-2-yl]thiophene-3-carboxamide Chemical compound C1C[C@@H](C)N(CCC)CC(=O)[C@H]1NC(=O)[C@@H](NC(=O)C1=CSC=C1)CC1CCCCC1 IWXKVAKADOQHIQ-QMMLZNLJSA-N 0.000 claims description 2
- GEPPKURZODOQJJ-HOJAQTOUSA-N n-[(2s)-4-methyl-1-[[(4s,7r)-7-methyl-3-oxo-1-propylazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound C1C[C@@H](C)N(CCC)CC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)C1=CC2=CC=CC=C2O1 GEPPKURZODOQJJ-HOJAQTOUSA-N 0.000 claims description 2
- BWYBBMQLUKXECQ-JBACZVJFSA-N n-[(2s)-4-methyl-1-[[(4s,7s)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound N1([C@@H](C)CC[C@@H](C(C1)=O)NC(=O)[C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)S(=O)(=O)C1=CC=CC=N1 BWYBBMQLUKXECQ-JBACZVJFSA-N 0.000 claims description 2
- MEOOYFQGWKAPBI-BVAGGSTKSA-N n-[(4s,7r)-1-(cyclohexylmethyl)-7-methyl-3-oxoazepan-4-yl]-1-(3-cyclohexylpropanoylamino)cyclohexane-1-carboxamide Chemical compound N([C@H]1CC[C@H](N(CC1=O)CC1CCCCC1)C)C(=O)C1(NC(=O)CCC2CCCCC2)CCCCC1 MEOOYFQGWKAPBI-BVAGGSTKSA-N 0.000 claims description 2
- JHVBDUGYTWTWBN-QPPBQGQZSA-N n-[1-[[(4s,7r)-1-(cyclohexylmethyl)-7-methyl-3-oxoazepan-4-yl]carbamoyl]cyclohexyl]-1-benzofuran-2-carboxamide Chemical compound N([C@H]1CC[C@H](N(CC1=O)CC1CCCCC1)C)C(=O)C1(NC(=O)C=2OC3=CC=CC=C3C=2)CCCCC1 JHVBDUGYTWTWBN-QPPBQGQZSA-N 0.000 claims description 2
- SFBZZCYKACGZCM-CTNGQTDRSA-N n-[1-[[(4s,7r)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]carbamoyl]cyclohexyl]-1-benzofuran-2-carboxamide Chemical compound N([C@H]1CC[C@H](N(CC1=O)S(=O)(=O)C=1N=CC=CC=1)C)C(=O)C1(NC(=O)C=2OC3=CC=CC=C3C=2)CCCCC1 SFBZZCYKACGZCM-CTNGQTDRSA-N 0.000 claims description 2
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 claims description 2
- PJGONEXTSXVJPE-FYZZASKESA-N tert-butyl n-[(2s)-1-[[(3r,4r,7s)-1-(benzenesulfonyl)-3-hydroxy-7-methylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1[C@@H](O)[C@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC[C@H](C)N1S(=O)(=O)C1=CC=CC=C1 PJGONEXTSXVJPE-FYZZASKESA-N 0.000 claims description 2
- JNMCOUZTZNWVRG-LJISPDSOSA-N tert-butyl n-[(2s)-1-[[(3r,4r,7s)-3-hydroxy-7-methylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]1CC[C@H](C)NC[C@H]1O JNMCOUZTZNWVRG-LJISPDSOSA-N 0.000 claims description 2
- GURJLSFZKPBFSI-CRBWNDHFSA-N tert-butyl n-[(2s)-1-[[(3s,4s,7r)-3-hydroxy-7-methyl-2-pyridin-2-ylsulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound O[C@H]1[C@@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC[C@@H](C)NC1S(=O)(=O)C1=CC=CC=N1 GURJLSFZKPBFSI-CRBWNDHFSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 claims 4
- ICGSJPWJFCKKLP-NJAFHUGGSA-N (2S)-2-amino-3-cyclohexyl-N-[(4S,7R)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]propanamide Chemical compound C([C@H](N)C(=O)N[C@H]1CC[C@H](N(CC1=O)S(=O)(=O)C=1N=CC=CC=1)C)C1CCCCC1 ICGSJPWJFCKKLP-NJAFHUGGSA-N 0.000 claims 2
- QRUPEWOLZIXLJG-UGUYLWEFSA-N (2S)-2-amino-N-[(3S,4S,7R)-3-hydroxy-7-methyl-1-pyridin-2-ylsulfonylazepan-4-yl]-4-methylpentanamide Chemical compound C1[C@H](O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC[C@@H](C)N1S(=O)(=O)C1=CC=CC=N1 QRUPEWOLZIXLJG-UGUYLWEFSA-N 0.000 claims 2
- 241000222732 Leishmania major Species 0.000 claims 2
- 201000006592 giardiasis Diseases 0.000 claims 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims 2
- 230000036281 parasite infection Effects 0.000 claims 2
- FJCGGXMBJOEQOA-ILXRZTDVSA-N (2S)-2-amino-4,4-dimethyl-N-[(4S,7R)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]pentanamide Chemical compound C[C@@H]1CC[C@H](NC(=O)[C@@H](N)CC(C)(C)C)C(=O)CN1S(=O)(=O)C1=CC=CC=N1 FJCGGXMBJOEQOA-ILXRZTDVSA-N 0.000 claims 1
- OQWVUMWJGRYYAO-QLFBSQMISA-N (2S)-2-amino-4-methyl-N-[(4R,7R)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]pentanamide Chemical compound C1C(=O)[C@H](NC(=O)[C@@H](N)CC(C)C)CC[C@@H](C)N1S(=O)(=O)C1=CC=CC=N1 OQWVUMWJGRYYAO-QLFBSQMISA-N 0.000 claims 1
- IPCCAASWTRQQGQ-GJGLBJJNSA-N (2r)-2-[[4-[[(2s)-2-(1-benzofuran-2-carbonylamino)-4-methylpentanoyl]amino]-3-oxoazepane-1-carbonyl]amino]-4-methylpentanoic acid Chemical compound O=C1CN(C(=O)N[C@H](CC(C)C)C(O)=O)CCCC1NC(=O)[C@H](CC(C)C)NC(=O)C1=CC2=CC=CC=C2O1 IPCCAASWTRQQGQ-GJGLBJJNSA-N 0.000 claims 1
- CHAYLTJYSWEUAP-XCRWMPKNSA-N (2r)-4-methyl-n-[(4s,7r)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]-2-(3-phenylphenyl)pentanamide Chemical compound N1([C@H](C)CC[C@@H](C(C1)=O)NC(=O)[C@H](CC(C)C)C=1C=C(C=CC=1)C=1C=CC=CC=1)S(=O)(=O)C1=CC=CC=N1 CHAYLTJYSWEUAP-XCRWMPKNSA-N 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- ZASONMYYTKMHDG-UHFFFAOYSA-N 1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound N1=C(C=CC=C1)S(=O)(=O)N1CC(CCCC1)O ZASONMYYTKMHDG-UHFFFAOYSA-N 0.000 claims 1
- QIKGGDCADJHDGD-UHFFFAOYSA-N 4-methyl-2-(propanoylamino)pentanoic acid Chemical compound CCC(=O)NC(C(O)=O)CC(C)C QIKGGDCADJHDGD-UHFFFAOYSA-N 0.000 claims 1
- UNXZRFSDYNTDQN-HZEGPAAWSA-N C[C@@H]1CC[C@@H]([C@H](CN1C(=O)N2CCOCC2)O)NC(=O)[C@@H](CC(C)C)C3=C(OC4=CC=CC=C43)C(=O)N Chemical compound C[C@@H]1CC[C@@H]([C@H](CN1C(=O)N2CCOCC2)O)NC(=O)[C@@H](CC(C)C)C3=C(OC4=CC=CC=C43)C(=O)N UNXZRFSDYNTDQN-HZEGPAAWSA-N 0.000 claims 1
- DIVRFQVRXXTZGB-DVMWJLJYSA-N C[C@@H]1CC[C@@H]([C@H](CN1S(=O)(=O)C2=NC=C(C=C2)C(F)(F)F)O)NC(=O)[C@@H](CC(C)C)C3=C(OC4=C3C=C(C=C4)F)C(=O)N Chemical compound C[C@@H]1CC[C@@H]([C@H](CN1S(=O)(=O)C2=NC=C(C=C2)C(F)(F)F)O)NC(=O)[C@@H](CC(C)C)C3=C(OC4=C3C=C(C=C4)F)C(=O)N DIVRFQVRXXTZGB-DVMWJLJYSA-N 0.000 claims 1
- DLXIMUPJBHIUGA-YSHGAJCASA-N C[C@H](CC[C@@H]([C@H](C1)O)NC([C@H](CC(C)(C)C)C(SC=C2)=C2C(N)=O)=O)N1S(C1=NC=CC=C1)(=O)=O Chemical compound C[C@H](CC[C@@H]([C@H](C1)O)NC([C@H](CC(C)(C)C)C(SC=C2)=C2C(N)=O)=O)N1S(C1=NC=CC=C1)(=O)=O DLXIMUPJBHIUGA-YSHGAJCASA-N 0.000 claims 1
- FCOLHUGWJMBZLY-VQVTYTSYSA-N N(=[N+]=[N-])[C@H]1CC[C@H](N(C[C@@H]1O)C(=O)O)C Chemical compound N(=[N+]=[N-])[C@H]1CC[C@H](N(C[C@@H]1O)C(=O)O)C FCOLHUGWJMBZLY-VQVTYTSYSA-N 0.000 claims 1
- CNVXGUFWSFAATI-GIVPXCGWSA-N benzyl (2r,5s)-2-methyl-5-[[(2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]-6-oxoazepane-1-carboxylate Chemical compound C1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC[C@@H](C)N1C(=O)OCC1=CC=CC=C1 CNVXGUFWSFAATI-GIVPXCGWSA-N 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- STPXQTSZFAJCCI-OIBXWCBGSA-N n-[(2s)-3-cyclohexyl-1-[[(4s,7r)-7-methyl-3-oxo-1-propylazepan-4-yl]amino]-1-oxopropan-2-yl]-1-benzofuran-2-carboxamide Chemical compound C1C[C@@H](C)N(CCC)CC(=O)[C@H]1NC(=O)[C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC1CCCCC1 STPXQTSZFAJCCI-OIBXWCBGSA-N 0.000 claims 1
- BWYBBMQLUKXECQ-TYPHKJRUSA-N n-[(2s)-4-methyl-1-[[(4r,7s)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound N1([C@@H](C)CC[C@H](C(C1)=O)NC(=O)[C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)S(=O)(=O)C1=CC=CC=N1 BWYBBMQLUKXECQ-TYPHKJRUSA-N 0.000 claims 1
- TUCHPHMJJDUWLH-YGOYIFOWSA-N n-[(2s)-4-methyl-1-[[(4s,7r)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]amino]-1-oxopentan-2-yl]quinoline-3-carboxamide Chemical compound N1([C@H](C)CC[C@@H](C(C1)=O)NC(=O)[C@@H](NC(=O)C=1C=C2C=CC=CC2=NC=1)CC(C)C)S(=O)(=O)C1=CC=CC=N1 TUCHPHMJJDUWLH-YGOYIFOWSA-N 0.000 claims 1
- BOZRBGPSKORPJK-YGOYIFOWSA-N n-[(2s)-4-methyl-1-[[(4s,7r)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]amino]-1-oxopentan-2-yl]quinoline-6-carboxamide Chemical compound N1([C@H](C)CC[C@@H](C(C1)=O)NC(=O)[C@@H](NC(=O)C=1C=C2C=CC=NC2=CC=1)CC(C)C)S(=O)(=O)C1=CC=CC=N1 BOZRBGPSKORPJK-YGOYIFOWSA-N 0.000 claims 1
- YAUUTUXLZAGMCN-XGKIILMVSA-N n-[(3r,4r,7r)-3-hydroxy-7-methyl-1-pyridin-2-ylsulfonylazepan-4-yl]-4-methyl-2-(3-phenylphenyl)pentanamide Chemical compound N1([C@H](C)CC[C@H]([C@@H](C1)O)NC(=O)C(CC(C)C)C=1C=C(C=CC=1)C=1C=CC=CC=1)S(=O)(=O)C1=CC=CC=N1 YAUUTUXLZAGMCN-XGKIILMVSA-N 0.000 claims 1
- 208000024693 gingival disease Diseases 0.000 abstract description 7
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 abstract description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 abstract description 6
- 208000010191 Osteitis Deformans Diseases 0.000 abstract description 5
- 208000027868 Paget disease Diseases 0.000 abstract description 5
- 208000027202 mammary Paget disease Diseases 0.000 abstract description 5
- 208000029725 Metabolic bone disease Diseases 0.000 abstract description 3
- 206010020584 Hypercalcaemia of malignancy Diseases 0.000 abstract description 2
- 206010003246 arthritis Diseases 0.000 abstract description 2
- 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 abstract description 2
- 208000030136 Marchiafava-Bignami Disease Diseases 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 162
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- 239000011541 reaction mixture Substances 0.000 description 143
- 239000000243 solution Substances 0.000 description 110
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 92
- 235000019439 ethyl acetate Nutrition 0.000 description 76
- 238000005481 NMR spectroscopy Methods 0.000 description 70
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 61
- 239000000741 silica gel Substances 0.000 description 54
- 229910002027 silica gel Inorganic materials 0.000 description 54
- 239000012267 brine Substances 0.000 description 51
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 51
- 238000004949 mass spectrometry Methods 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 45
- 238000001819 mass spectrum Methods 0.000 description 45
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 238000000746 purification Methods 0.000 description 36
- VXGYRCVTBHVXMZ-UHFFFAOYSA-N quinoline-6-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CC=C21 VXGYRCVTBHVXMZ-UHFFFAOYSA-N 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- JQJOGAGLBDBMLU-UHFFFAOYSA-N pyridine-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=N1 JQJOGAGLBDBMLU-UHFFFAOYSA-N 0.000 description 32
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 102100024940 Cathepsin K Human genes 0.000 description 25
- 239000003112 inhibitor Substances 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
- 210000000988 bone and bone Anatomy 0.000 description 19
- 238000004811 liquid chromatography Methods 0.000 description 19
- 239000012044 organic layer Substances 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- MDXGYYOJGPFFJL-QMMMGPOBSA-N N(alpha)-t-butoxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-QMMMGPOBSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 16
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 15
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- 102000005600 Cathepsins Human genes 0.000 description 12
- 108010084457 Cathepsins Proteins 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 210000002997 osteoclast Anatomy 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000011734 sodium Substances 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 208000006386 Bone Resorption Diseases 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 230000024279 bone resorption Effects 0.000 description 10
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 8
- 230000010933 acylation Effects 0.000 description 8
- 238000005917 acylation reaction Methods 0.000 description 8
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 239000011984 grubbs catalyst Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- XZELWEMGWISCTP-UHFFFAOYSA-N 5-methoxy-1-benzofuran-2-carboxylic acid Chemical compound COC1=CC=C2OC(C(O)=O)=CC2=C1 XZELWEMGWISCTP-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 238000010511 deprotection reaction Methods 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 238000002390 rotary evaporation Methods 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- GVZXSZWCZGKLRS-UHFFFAOYSA-N thieno[3,2-b]thiophene-5-carboxylic acid Chemical compound S1C=CC2=C1C=C(C(=O)O)S2 GVZXSZWCZGKLRS-UHFFFAOYSA-N 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 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 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 108090000526 Papain Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- NTUAECGJTISEEG-SECBINFHSA-N benzyl n-[(2r)-1-iodopropan-2-yl]carbamate Chemical compound IC[C@@H](C)NC(=O)OCC1=CC=CC=C1 NTUAECGJTISEEG-SECBINFHSA-N 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- QEKVQYCTJHJBOF-UHFFFAOYSA-L ruthenium(2+);styrene;triphenylphosphane;dichloride Chemical compound Cl[Ru]Cl.C=CC1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QEKVQYCTJHJBOF-UHFFFAOYSA-L 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 150000002924 oxiranes Chemical class 0.000 description 5
- 229940055729 papain Drugs 0.000 description 5
- 235000019834 papain Nutrition 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- PNMBYKZJLBBZMD-UUCFBXCCSA-N (2S)-2-amino-4-methyl-N-(5-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)pentanamide Chemical compound C1C(=O)C(NC(=O)[C@@H](N)CC(C)C)C(C)CCN1S(=O)(=O)C1=CC=CC=N1 PNMBYKZJLBBZMD-UUCFBXCCSA-N 0.000 description 4
- URQQEIOTRWJXBA-QRPNPIFTSA-N (2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid;hydrate Chemical compound O.CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C URQQEIOTRWJXBA-QRPNPIFTSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 4
- 239000002852 cysteine proteinase inhibitor Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 4
- 235000019419 proteases Nutrition 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 4
- 125000003373 pyrazinyl group Chemical group 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- 150000003333 secondary alcohols Chemical class 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 4
- MSZQAQJBXGTSHP-NSHDSACASA-N (2s)-3-cyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1CCCCC1 MSZQAQJBXGTSHP-NSHDSACASA-N 0.000 description 3
- QCBZCEKWIGTIMT-UHFFFAOYSA-N 1,3-bis(sulfanyl)propan-2-one Chemical class SCC(=O)CS QCBZCEKWIGTIMT-UHFFFAOYSA-N 0.000 description 3
- JKBABFRRSREYBG-UHFFFAOYSA-N 4-methyl-2-(3-phenylphenyl)pentanoic acid Chemical compound CC(C)CC(C(O)=O)C1=CC=CC(C=2C=CC=CC=2)=C1 JKBABFRRSREYBG-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 241000222716 Crithidia Species 0.000 description 3
- NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 3
- 241000233872 Pneumocystis carinii Species 0.000 description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000004849 alkoxymethyl group Chemical group 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- AFPHMHSLDRPUSM-SECBINFHSA-N benzyl n-[(2r)-1-hydroxypropan-2-yl]carbamate Chemical compound OC[C@@H](C)NC(=O)OCC1=CC=CC=C1 AFPHMHSLDRPUSM-SECBINFHSA-N 0.000 description 3
- 210000002805 bone matrix Anatomy 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- XNMQEEKYCVKGBD-UHFFFAOYSA-N dimethylacetylene Natural products CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 3
- 108010052968 leupeptin Proteins 0.000 description 3
- CYSFUFRXDOAOMP-UHFFFAOYSA-M magnesium;prop-1-ene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C=C CYSFUFRXDOAOMP-UHFFFAOYSA-M 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 201000006938 muscular dystrophy Diseases 0.000 description 3
- BJXAXBQJGQUEIP-UHFFFAOYSA-N n-prop-2-enylhex-5-en-2-amine Chemical compound C=CCCC(C)NCC=C BJXAXBQJGQUEIP-UHFFFAOYSA-N 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 235000012736 patent blue V Nutrition 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 230000006103 sulfonylation Effects 0.000 description 3
- 238000005694 sulfonylation reaction Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- KMUFWTAFDZMALB-ZJUUUORDSA-N (4S,7R)-4-amino-7-methyl-1-pyridin-2-ylsulfonylazepan-3-one Chemical compound C[C@@H]1CC[C@H](N)C(=O)CN1S(=O)(=O)C1=CC=CC=N1 KMUFWTAFDZMALB-ZJUUUORDSA-N 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- OVBFMEVBMNZIBR-UHFFFAOYSA-N -2-Methylpentanoic acid Natural products CCCC(C)C(O)=O OVBFMEVBMNZIBR-UHFFFAOYSA-N 0.000 description 2
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
- URBHKVWOYIMKNO-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylic acid Chemical group CC(C)(C)OC(=O)NC1(C(O)=O)CCCCC1 URBHKVWOYIMKNO-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- FBPINGSGHKXIQA-UHFFFAOYSA-N 2-amino-3-(2-carboxyethylsulfanyl)propanoic acid Chemical compound OC(=O)C(N)CSCCC(O)=O FBPINGSGHKXIQA-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- OCZVQLJXCRTSQR-UHFFFAOYSA-N 3-methyl-5-pyridin-2-ylsulfonyl-8-oxa-5-azabicyclo[5.1.0]octane Chemical compound C1C(C)CC2OC2CN1S(=O)(=O)C1=CC=CC=N1 OCZVQLJXCRTSQR-UHFFFAOYSA-N 0.000 description 2
- KIJSABJSBHATSA-UHFFFAOYSA-N 4-amino-6-methyl-1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound C1C(C)CC(N)C(O)CN1S(=O)(=O)C1=CC=CC=N1 KIJSABJSBHATSA-UHFFFAOYSA-N 0.000 description 2
- OWFRWTPPOZSWLL-UHFFFAOYSA-N 5,6-difluoro-1-benzofuran-2-carboxylic acid Chemical compound FC1=C(F)C=C2OC(C(=O)O)=CC2=C1 OWFRWTPPOZSWLL-UHFFFAOYSA-N 0.000 description 2
- MRIFFPWOMKLYKZ-UHFFFAOYSA-N 5-(trifluoromethyl)pyridine-2-sulfonyl chloride Chemical compound FC(F)(F)C1=CC=C(S(Cl)(=O)=O)N=C1 MRIFFPWOMKLYKZ-UHFFFAOYSA-N 0.000 description 2
- YMUHUYBRWUUAJF-UHFFFAOYSA-N 5-cyclohexylpentanoic acid Chemical compound OC(=O)CCCCC1CCCCC1 YMUHUYBRWUUAJF-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 101710177066 Cathepsin O Proteins 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
- 241000223924 Eimeria Species 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- BDBGKYIBDXAVMX-UHFFFAOYSA-N Ethyl 2-methyl-4-pentenoate Chemical compound CCOC(=O)C(C)CC=C BDBGKYIBDXAVMX-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical class NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000037147 Hypercalcaemia Diseases 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000005865 alkene metathesis reaction Methods 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- CJKVNTNBIZCKJD-MRVWCRGKSA-N benzyl (2r,5r,6r)-5-amino-6-hydroxy-2-methylazepane-1-carboxylate Chemical compound C[C@@H]1CC[C@@H](N)[C@H](O)CN1C(=O)OCC1=CC=CC=C1 CJKVNTNBIZCKJD-MRVWCRGKSA-N 0.000 description 2
- DWKDPFXZJQTJHM-STQMWFEESA-N benzyl (3s,4s)-4-amino-3-hydroxyazepane-1-carboxylate Chemical group C1[C@H](O)[C@@H](N)CCCN1C(=O)OCC1=CC=CC=C1 DWKDPFXZJQTJHM-STQMWFEESA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical compound CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- UWCHSDIUMBNDLT-UHFFFAOYSA-L copper;methylsulfanylmethane;dibromide Chemical compound CSC.Br[Cu]Br UWCHSDIUMBNDLT-UHFFFAOYSA-L 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
- HJZLEGIHUQOJBA-UHFFFAOYSA-N cyclohexane propionic acid Chemical compound OC(=O)CCC1CCCCC1 HJZLEGIHUQOJBA-UHFFFAOYSA-N 0.000 description 2
- LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 2
- 210000004268 dentin Anatomy 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000006735 epoxidation reaction Methods 0.000 description 2
- JKTDAZYGVHGBEO-UHFFFAOYSA-N ethyl 3-methyl-4-nitrobutanoate Chemical compound CCOC(=O)CC(C)C[N+]([O-])=O JKTDAZYGVHGBEO-UHFFFAOYSA-N 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 230000000148 hypercalcaemia Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 2
- 210000005170 neoplastic cell Anatomy 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- KZVLNAGYSAKYMG-UHFFFAOYSA-N pyridine-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=N1 KZVLNAGYSAKYMG-UHFFFAOYSA-N 0.000 description 2
- UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical group 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- KAJOUAMKPIZUBD-RDBSUJKOSA-N (2R,5S)-2-methyl-5-[[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]-6-oxoazepane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CC[C@@H](C)N(C(O)=O)CC1=O KAJOUAMKPIZUBD-RDBSUJKOSA-N 0.000 description 1
- YSGAEXLPAYUHAK-QPSCCSFWSA-N (2R,5S,6S)-6-hydroxy-2-methyl-5-[[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]azepane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CC[C@@H](C)N(C(O)=O)C[C@@H]1O YSGAEXLPAYUHAK-QPSCCSFWSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- KJTIVHSZERGSJV-SNPRPXQTSA-N (2S)-2-amino-4-methyl-N-[(4S,7R)-7-methyl-3-oxo-1-[5-(trifluoromethyl)pyridin-2-yl]sulfonylazepan-4-yl]pentanamide Chemical compound C1C(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC[C@@H](C)N1S(=O)(=O)C1=CC=C(C(F)(F)F)C=N1 KJTIVHSZERGSJV-SNPRPXQTSA-N 0.000 description 1
- SUSCJDPKAMRSLQ-QGZVFWFLSA-N (2r)-2-[(3-phenylphenyl)methyl]pentanoic acid Chemical compound CCC[C@@H](C(O)=O)CC1=CC=CC(C=2C=CC=CC=2)=C1 SUSCJDPKAMRSLQ-QGZVFWFLSA-N 0.000 description 1
- SPVZHUGRMDRKAC-YFKPBYRVSA-N (2s)-2-(azaniumylmethyl)pentanoate Chemical compound CCC[C@@H](CN)C(O)=O SPVZHUGRMDRKAC-YFKPBYRVSA-N 0.000 description 1
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
- CUHKGCOOPJFXOX-GBAJDQEWSA-N (2s)-2-[[(2r,5s)-5-[[(2s)-2-(1-benzofuran-2-carbonylamino)-4-methylpentanoyl]amino]-2-methyl-6-oxoazepane-1-carbonyl]amino]-4-methylpentanoic acid Chemical compound C1C[C@@H](C)N(C(=O)N[C@@H](CC(C)C)C(O)=O)CC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)C1=CC2=CC=CC=C2O1 CUHKGCOOPJFXOX-GBAJDQEWSA-N 0.000 description 1
- GEDPJVGTIBEAAX-WDCUWTOYSA-N (2s)-2-amino-n-(3-hydroxy-5-methyl-1-pyridin-2-ylsulfonylazepan-4-yl)-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)C(C)CCN1S(=O)(=O)C1=CC=CC=N1 GEDPJVGTIBEAAX-WDCUWTOYSA-N 0.000 description 1
- CQHZIIXKMUVQGO-LURJTMIESA-N (2s)-2-isocyanato-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)N=C=O CQHZIIXKMUVQGO-LURJTMIESA-N 0.000 description 1
- FTPWFSBSXZYZKR-XRGAULLZSA-N (2s)-3-cyclohexyl-n-[(3s,4s,7r)-3-hydroxy-7-methylazepan-4-yl]-2-methylpropanamide Chemical compound C([C@H](C)C(=O)N[C@@H]1[C@H](CN[C@H](C)CC1)O)C1CCCCC1 FTPWFSBSXZYZKR-XRGAULLZSA-N 0.000 description 1
- ZIGPWBCFIWAHKT-GMTAPVOTSA-N (3r,4r,7r)-4-amino-7-methyl-1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound C[C@@H]1CC[C@@H](N)[C@H](O)CN1S(=O)(=O)C1=CC=CC=N1 ZIGPWBCFIWAHKT-GMTAPVOTSA-N 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- QBYPSSMUKCERJK-UHFFFAOYSA-N 1-(2-methylpropyl)-3-phenylbenzene Chemical group CC(C)CC1=CC=CC(C=2C=CC=CC=2)=C1 QBYPSSMUKCERJK-UHFFFAOYSA-N 0.000 description 1
- QVIKGEPIBIFRCI-GGAORHGYSA-N 1-(3-cyclohexylpropanoylamino)-n-[(4s,7r)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]cyclohexane-1-carboxamide Chemical compound N([C@H]1CC[C@H](N(CC1=O)S(=O)(=O)C=1N=CC=CC=1)C)C(=O)C1(NC(=O)CCC2CCCCC2)CCCCC1 QVIKGEPIBIFRCI-GGAORHGYSA-N 0.000 description 1
- UGYPXRGQGNLWOF-UHFFFAOYSA-N 1-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CCN=C=NC(CC)N(C)C UGYPXRGQGNLWOF-UHFFFAOYSA-N 0.000 description 1
- VTYMUYCDVOZKDN-CABCVRRESA-N 1-amino-N-[(4S,7R)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]cyclohexane-1-carboxamide Chemical compound N([C@H]1CC[C@H](N(CC1=O)S(=O)(=O)C=1N=CC=CC=1)C)C(=O)C1(N)CCCCC1 VTYMUYCDVOZKDN-CABCVRRESA-N 0.000 description 1
- QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 description 1
- DYSJMQABFPKAQM-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=C1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 description 1
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical group [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 1
- PVISTSWZFOZJOI-UHFFFAOYSA-N 1-hydroxyazepane Chemical compound ON1CCCCCC1 PVISTSWZFOZJOI-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical class CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- YWUNGYFXNDOGNZ-UHFFFAOYSA-N 1-phenylpiperazin-2-one Chemical compound O=C1CNCCN1C1=CC=CC=C1 YWUNGYFXNDOGNZ-UHFFFAOYSA-N 0.000 description 1
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical compound C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 1
- YAXQKAGUVNHYNL-UHFFFAOYSA-N 1-pyridin-2-ylpiperazin-2-one Chemical compound O=C1CNCCN1C1=CC=CC=N1 YAXQKAGUVNHYNL-UHFFFAOYSA-N 0.000 description 1
- RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 1
- NQIBQILAMKZKFE-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3-fluoropyridine Chemical compound FC1=CC=C(Br)C=C1C1=NC=CC=C1F NQIBQILAMKZKFE-UHFFFAOYSA-N 0.000 description 1
- XNIOWJUQPMKCIJ-UHFFFAOYSA-N 2-(benzylamino)ethanol Chemical compound OCCNCC1=CC=CC=C1 XNIOWJUQPMKCIJ-UHFFFAOYSA-N 0.000 description 1
- QRHYCLBYHIKSTA-UHFFFAOYSA-N 2-(butanoylamino)-4-methylpentanoic acid Chemical compound CCCC(=O)NC(C(O)=O)CC(C)C QRHYCLBYHIKSTA-UHFFFAOYSA-N 0.000 description 1
- IDEYZABHVQLHAF-XQRVVYSFSA-N 2-Methyl-2-pentenal Chemical compound CC\C=C(\C)C=O IDEYZABHVQLHAF-XQRVVYSFSA-N 0.000 description 1
- IDEYZABHVQLHAF-UHFFFAOYSA-N 2-Methyl-2-pentenal Natural products CCC=C(C)C=O IDEYZABHVQLHAF-UHFFFAOYSA-N 0.000 description 1
- DRKRYNDEHDRFMJ-UHFFFAOYSA-N 2-[benzyl-(3-methyl-4-nitrobutyl)amino]ethanol Chemical compound [O-][N+](=O)CC(C)CCN(CCO)CC1=CC=CC=C1 DRKRYNDEHDRFMJ-UHFFFAOYSA-N 0.000 description 1
- RPXFDOOFVNTCQA-UHFFFAOYSA-N 2-cyclohexylbutanoic acid Chemical compound CCC(C(O)=O)C1CCCCC1 RPXFDOOFVNTCQA-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- AJEUJXWLOADTKA-UHFFFAOYSA-N 2-piperidin-1-ylpyridine Chemical compound C1CCCCN1C1=CC=CC=N1 AJEUJXWLOADTKA-UHFFFAOYSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- CGWOEOXQHIMZEQ-UHFFFAOYSA-N 3-[1-[[4-(2-phenylquinolin-3-yl)phenyl]methyl]piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound OC1=NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=CC2=CC=CC=C2N=C1C1=CC=CC=C1 CGWOEOXQHIMZEQ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
- ZYJSTSMEUKNCEV-UHFFFAOYSA-N 3-diazo-1-diazonioprop-1-en-2-olate Chemical class [N-]=[N+]=CC(=O)C=[N+]=[N-] ZYJSTSMEUKNCEV-UHFFFAOYSA-N 0.000 description 1
- BYOSZULJWYKCQL-UHFFFAOYSA-N 3-methyl-4-nitrobutanal Chemical compound O=CCC(C)C[N+]([O-])=O BYOSZULJWYKCQL-UHFFFAOYSA-N 0.000 description 1
- GHNBWZWSJFIMQO-UHFFFAOYSA-N 3-methylazepin-2-one Chemical compound CC1=CC=CC=NC1=O GHNBWZWSJFIMQO-UHFFFAOYSA-N 0.000 description 1
- ZODAEGCLBQIRLR-UHFFFAOYSA-N 3-methylfuro[3,2-b]pyridine Chemical compound C1=CN=C2C(C)=COC2=C1 ZODAEGCLBQIRLR-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- GWFBGNJDFDFSAW-UHFFFAOYSA-N 4-azido-6-methyl-1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound C1C(C)CC(N=[N+]=[N-])C(O)CN1S(=O)(=O)C1=CC=CC=N1 GWFBGNJDFDFSAW-UHFFFAOYSA-N 0.000 description 1
- RJFMKOMFFWXGDS-UHFFFAOYSA-N 4-fluoro-3-methyl-1-benzofuran-2-carboxylic acid Chemical compound C1=CC(F)=C2C(C)=C(C(O)=O)OC2=C1 RJFMKOMFFWXGDS-UHFFFAOYSA-N 0.000 description 1
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 1
- GMIDGDXRCTUPNM-UHFFFAOYSA-N 5-fluoro-3-methyl-1-benzofuran-2-carboxylic acid Chemical compound C1=C(F)C=C2C(C)=C(C(O)=O)OC2=C1 GMIDGDXRCTUPNM-UHFFFAOYSA-N 0.000 description 1
- RNDVGJZUHCKENF-UHFFFAOYSA-N 5-hexen-2-one Chemical compound CC(=O)CCC=C RNDVGJZUHCKENF-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 239000004475 Arginine Chemical class 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Chemical class OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000035101 Aspartic proteases Human genes 0.000 description 1
- 108091005502 Aspartic proteases Proteins 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 208000018083 Bone metabolism disease Diseases 0.000 description 1
- 229940078581 Bone resorption inhibitor Drugs 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- RUMLVVRPICYZCA-HOJAQTOUSA-N CC(C)C[C@H](C(N[C@@H](CC[C@@H](C)N(C1)S(C2=NC=CC=C2)(=O)=O)C1=O)=O)C1=C(C(N)=O)OC2=C1C=CC=C2 Chemical compound CC(C)C[C@H](C(N[C@@H](CC[C@@H](C)N(C1)S(C2=NC=CC=C2)(=O)=O)C1=O)=O)C1=C(C(N)=O)OC2=C1C=CC=C2 RUMLVVRPICYZCA-HOJAQTOUSA-N 0.000 description 1
- WQVLLPUBUCOGLQ-HOJAQTOUSA-N C[C@@H]1CC[C@@H](C(=O)CN1C(=O)N2CCOCC2)NC(=O)[C@@H](CC(C)C)C3=C(OC4=CC=CC=C43)C(=O)N Chemical compound C[C@@H]1CC[C@@H](C(=O)CN1C(=O)N2CCOCC2)NC(=O)[C@@H](CC(C)C)C3=C(OC4=CC=CC=C43)C(=O)N WQVLLPUBUCOGLQ-HOJAQTOUSA-N 0.000 description 1
- GKGVDVPQRGARPQ-VQVTYTSYSA-N C[C@@H]1CC[C@H]2[C@@H](O2)CN1C(=O)O Chemical compound C[C@@H]1CC[C@H]2[C@@H](O2)CN1C(=O)O GKGVDVPQRGARPQ-VQVTYTSYSA-N 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229940122156 Cathepsin K inhibitor Drugs 0.000 description 1
- 101000749287 Clitocybe nebularis Clitocypin Proteins 0.000 description 1
- 101000767029 Clitocybe nebularis Clitocypin-1 Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000015833 Cystatin Human genes 0.000 description 1
- 229940094664 Cysteine protease inhibitor Drugs 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- ZFDIRQKJPRINOQ-HWKANZROSA-N Ethyl crotonate Chemical compound CCOC(=O)\C=C\C ZFDIRQKJPRINOQ-HWKANZROSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- OECJOWYHFHHPMC-UHFFFAOYSA-N FC1=C(OC2=C1C=CC=C2)C(=O)O Chemical compound FC1=C(OC2=C1C=CC=C2)C(=O)O OECJOWYHFHHPMC-UHFFFAOYSA-N 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 208000002966 Giant Cell Tumor of Bone Diseases 0.000 description 1
- 108091020100 Gingipain Cysteine Endopeptidases Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Chemical class 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 238000006842 Henry reaction Methods 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical class OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical class C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical class NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical class OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical class OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical class OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical class CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical class CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical class OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical class CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Chemical class NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Chemical class 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- 102000009890 Osteonectin Human genes 0.000 description 1
- 108010077077 Osteonectin Proteins 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100036829 Probable peptidyl-tRNA hydrolase Human genes 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical class OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000006270 Proton Pumps Human genes 0.000 description 1
- 108010083204 Proton Pumps Proteins 0.000 description 1
- 101000933967 Pseudomonas phage KPP25 Major capsid protein Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 229940124325 anabolic agent Drugs 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Chemical class OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical class OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical compound ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- DGEXKPJDVGYJKO-KWCYVHTRSA-N benzyl (1s,4r,7r)-4-methyl-8-oxa-5-azabicyclo[5.1.0]octane-5-carboxylate Chemical compound C([C@H]1O[C@H]1CC[C@H]1C)N1C(=O)OCC1=CC=CC=C1 DGEXKPJDVGYJKO-KWCYVHTRSA-N 0.000 description 1
- ZUPJXLVQCFBGHY-UHFFFAOYSA-N benzyl azepane-1-carboxylate Chemical compound C1CCCCCN1C(=O)OCC1=CC=CC=C1 ZUPJXLVQCFBGHY-UHFFFAOYSA-N 0.000 description 1
- AFPHMHSLDRPUSM-UHFFFAOYSA-N benzyl n-(1-hydroxypropan-2-yl)carbamate Chemical compound OCC(C)NC(=O)OCC1=CC=CC=C1 AFPHMHSLDRPUSM-UHFFFAOYSA-N 0.000 description 1
- ZZGDDBWFXDMARY-SVBPBHIXSA-N benzyl n-[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC1=CC=2OC(=O)C=C(C=2C=C1)C)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 ZZGDDBWFXDMARY-SVBPBHIXSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Chemical class OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000002617 bone density conservation agent Substances 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- MSZJEPVVQWJCIF-UHFFFAOYSA-N butylazanide Chemical compound CCCC[NH-] MSZJEPVVQWJCIF-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000008355 cartilage degradation Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000003541 chondroclast Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 108090000711 cruzipain Proteins 0.000 description 1
- 150000001942 cyclopropanes Chemical class 0.000 description 1
- 108050004038 cystatin Proteins 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- SWIOGPHKKZUDIC-UHFFFAOYSA-L dichlororuthenium(2+) Chemical compound Cl[Ru+2]Cl SWIOGPHKKZUDIC-UHFFFAOYSA-L 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000002223 garnet Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Chemical class OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 125000004836 hexamethylene group Chemical class [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Chemical class OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N hydrofluoric acid Substances F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Chemical class CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 208000036546 leukodystrophy Diseases 0.000 description 1
- 238000012886 linear function Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- AWIJRPNMLHPLNC-UHFFFAOYSA-N methanethioic s-acid Chemical class SC=O AWIJRPNMLHPLNC-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Chemical class 0.000 description 1
- NYVDNVCZHTXXMW-UHFFFAOYSA-N methyl n-butylcarbamate Chemical compound CCCCNC(=O)OC NYVDNVCZHTXXMW-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000005088 multinucleated cell Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- QPJSUIGXIBEQAC-UHFFFAOYSA-N n-(2,4-dichloro-5-propan-2-yloxyphenyl)acetamide Chemical compound CC(C)OC1=CC(NC(C)=O)=C(Cl)C=C1Cl QPJSUIGXIBEQAC-UHFFFAOYSA-N 0.000 description 1
- BWYBBMQLUKXECQ-NRSPTQNISA-N n-[(2s)-4-methyl-1-[[(4r,7r)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound N1([C@H](C)CC[C@H](C(C1)=O)NC(=O)[C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)S(=O)(=O)C1=CC=CC=N1 BWYBBMQLUKXECQ-NRSPTQNISA-N 0.000 description 1
- RXNMSPOIOOUCPW-ZODMCCGTSA-N n-[1-[[(3s,4s,7r)-1-(cyclohexylmethyl)-3-hydroxy-7-methylazepan-4-yl]carbamoyl]cyclohexyl]-1-benzofuran-2-carboxamide Chemical compound N([C@H]1CC[C@H](N(C[C@@H]1O)CC1CCCCC1)C)C(=O)C1(NC(=O)C=2OC3=CC=CC=C3C=2)CCCCC1 RXNMSPOIOOUCPW-ZODMCCGTSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004957 naphthylene group Chemical group 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 230000003349 osteoarthritic effect Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000004817 pentamethylene group Chemical class [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical class OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920003217 poly(methylsilsesquioxane) Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- IAUBZYYUBMBVPI-UHFFFAOYSA-N pyridine;sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O.C1=CC=NC=C1 IAUBZYYUBMBVPI-UHFFFAOYSA-N 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- QRDZFPUVLYEQTA-UHFFFAOYSA-N quinoline-8-carboxylic acid Chemical group C1=CN=C2C(C(=O)O)=CC=CC2=C1 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- BXHSOHKVVCAVCF-POAOYLCXSA-N tert-butyl n-[(2s)-1-[(3-hydroxy-5-methyl-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)C(C)CCN1S(=O)(=O)C1=CC=CC=N1 BXHSOHKVVCAVCF-POAOYLCXSA-N 0.000 description 1
- SADYQPDODRPRNE-IBLUKRHDSA-N tert-butyl n-[(2s)-1-[(3-hydroxy-5-methylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(C)C)C(=O)NC1C(C)CCNCC1O SADYQPDODRPRNE-IBLUKRHDSA-N 0.000 description 1
- GUHKZDLPLWKJIJ-MGPQQGTHSA-N tert-butyl n-[(3r,4r,7r)-3-hydroxy-7-methyl-1-pyridin-2-ylsulfonylazepan-4-yl]carbamate Chemical compound C[C@@H]1CC[C@@H](NC(=O)OC(C)(C)C)[C@H](O)CN1S(=O)(=O)C1=CC=CC=N1 GUHKZDLPLWKJIJ-MGPQQGTHSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- VJYJJHQEVLEOFL-UHFFFAOYSA-N thieno[3,2-b]thiophene Chemical compound S1C=CC2=C1C=CS2 VJYJJHQEVLEOFL-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 description 1
- DAUYIKBTMNZABP-UHFFFAOYSA-N thiophene-3-carboxamide Chemical compound NC(=O)C=1C=CSC=1 DAUYIKBTMNZABP-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000008354 tissue degradation Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/14—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/04—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US19100000P | 2000-03-21 | 2000-03-21 | |
US20634100P | 2000-05-23 | 2000-05-23 | |
US21175900P | 2000-06-14 | 2000-06-14 | |
US21744500P | 2000-07-10 | 2000-07-10 | |
PCT/US2001/007094 WO2001070232A1 (en) | 2000-03-21 | 2001-03-07 | Protease inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
SK13632002A3 true SK13632002A3 (sk) | 2003-02-04 |
Family
ID=27497873
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1363-2002A SK13632002A3 (sk) | 2000-03-21 | 2001-03-07 | C1-6-alkyl-4-amino-azepán-3-ónové zlúčeniny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom, ich použitie a medziprodukty |
Country Status (26)
Country | Link |
---|---|
US (2) | US7071184B2 (no) |
EP (1) | EP1307203A4 (no) |
JP (1) | JP2003527429A (no) |
KR (1) | KR20020082896A (no) |
CN (1) | CN1416346A (no) |
AP (1) | AP1540A (no) |
AR (1) | AR032877A1 (no) |
AU (2) | AU4344101A (no) |
BG (1) | BG106962A (no) |
BR (1) | BR0109356A (no) |
CA (1) | CA2404206A1 (no) |
CZ (1) | CZ20023168A3 (no) |
DZ (1) | DZ3318A1 (no) |
EA (1) | EA005893B1 (no) |
HU (1) | HUP0300068A2 (no) |
IL (1) | IL150964A0 (no) |
MX (1) | MXPA02009305A (no) |
MY (1) | MY141596A (no) |
NO (1) | NO20024528L (no) |
NZ (1) | NZ520588A (no) |
OA (1) | OA12323A (no) |
PE (1) | PE20011233A1 (no) |
PL (1) | PL357727A1 (no) |
SK (1) | SK13632002A3 (no) |
UY (1) | UY26625A1 (no) |
WO (1) | WO2001070232A1 (no) |
Families Citing this family (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020128476A1 (en) * | 1996-08-08 | 2002-09-12 | Smithkline Beecham Corporation | Inhibitors of cysteine protease |
US20030144175A1 (en) | 1998-12-23 | 2003-07-31 | Smithkline Beecham Corporation | Protease inhibitors |
EP1229914A4 (en) | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
WO2001034600A1 (en) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
WO2001034599A1 (en) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
NZ520588A (en) | 2000-03-21 | 2004-06-25 | Smithkline Beecham Corp | Protease inhibitors |
CO5280093A1 (es) * | 2000-04-18 | 2003-05-30 | Smithkline Beecham Corp | Metodos de tratamiento |
CO5280088A1 (es) * | 2000-04-18 | 2003-05-30 | Smithkline Beecham Corp | Inhibidores de proteasa |
EP1320370A4 (en) * | 2000-09-01 | 2008-10-22 | Smithkline Beecham Corp | TREATMENT METHOD |
HUP0301964A3 (en) * | 2000-11-22 | 2007-09-28 | Smithkline Beecham Corp | Protease inhibitors |
AU2002360409A1 (en) * | 2001-11-21 | 2003-06-10 | Smithkline Beecham Corporation | Methods and intermediates for the synthesis of azepines |
EP1511745A4 (en) * | 2002-05-22 | 2006-11-15 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
WO2004033445A1 (en) * | 2002-10-08 | 2004-04-22 | Merck Frosst Canada & Co. | 4-amino-azepan-3-one compounds as cathepsin k inhibitors useful in the treatment of osteoporosis |
US20040192674A1 (en) * | 2003-02-14 | 2004-09-30 | Marquis Robert W. | Cathepsin L inhibitors |
WO2005069981A2 (en) * | 2004-01-23 | 2005-08-04 | Smithkline Beecham Corporation | Method of preparation of benzofuran-2-carboxylic acid {(s)-3-methyl-1-[(4s, 7r)-7methyl-3-oxo-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-butyl}-amide |
KR100603014B1 (ko) * | 2004-07-21 | 2006-07-24 | 황호연 | 라벨용 포장필름의 제조방법, 상기 제조방법으로 제조된라벨용 포장필름 및 상기 포장필름의 사용방법 |
WO2006042150A1 (en) * | 2004-10-07 | 2006-04-20 | Vitae Pharmaceuticals, Inc. | Diaminoalkane aspartic protease inhibitors |
PE20070171A1 (es) * | 2005-06-30 | 2007-03-08 | Boehringer Ingelheim Int | GLICINAMIDAS SUSTITUIDAS CON EFECTO ANTITROMBOTICO E INHIBIDOR DEL FACTOR Xa |
TWI411607B (zh) * | 2005-11-14 | 2013-10-11 | Vitae Pharmaceuticals Inc | 天門冬胺酸蛋白酶抑制劑 |
CL2007002689A1 (es) | 2006-09-18 | 2008-04-18 | Vitae Pharmaceuticals Inc | Compuestos derivados de piperidin-1-carboxamida, inhibidores de la renina; compuestos intermediarios; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como hipertension, insuficiencia cardiaca, fibrosis cardiaca, entre otras. |
KR20100023948A (ko) | 2007-06-08 | 2010-03-04 | 닛뽕 케미파 가부시키가이샤 | 뇌동맥류의 치료 또는 예방약 |
EP2167609A1 (en) * | 2007-06-20 | 2010-03-31 | Vitae Pharmaceuticals, Inc. | Renin inhibitors |
EP2170815A2 (en) * | 2007-06-20 | 2010-04-07 | Vitae Pharmaceuticals, Inc. | Renin inhibitors |
WO2009054454A1 (ja) | 2007-10-24 | 2009-04-30 | National University Corporation Tokyo Medical And Dental University | カテプシン阻害剤を有効成分として含有するToll様受容体のシグナル伝達の調整剤 |
EP2240491B1 (en) | 2008-01-09 | 2015-07-15 | Amura Therapeutics Limited | TETRAHYDROFURO(2,3-b)PYRROL-3-ONE DERIVATIVES AS INHIBITORS OF CYSTEINE PROTEINASES |
CA2727987A1 (en) * | 2008-06-20 | 2009-12-23 | Vitae Pharmaceuticals, Inc. | Renin inhibitors and method of use thereof |
MX2010014557A (es) * | 2008-06-26 | 2011-02-15 | Vitae Pharmaceuticals Inc | Sales de 2-((r)-(3-clorofenil)((r)-1-((s)-2-(metilamino)-3-((r)-te trahidro-2h-piran-3-il)propilcarbamoil)piperidin-3-il)metoxi)etil carbamato de metilo. |
AR077692A1 (es) * | 2009-08-06 | 2011-09-14 | Vitae Pharmaceuticals Inc | Sales de 2-((r)-(3-clorofenil) ((r)-1-((s) -2-(metilamino)-3-((r)-tetrahidro-2h-piran-3-il) propilcarbamoil) piperidin -3-il) metoxi) etilcarbamato de metilo |
US9943522B2 (en) | 2011-05-16 | 2018-04-17 | Bayer Intellectual Property Gmbh | Use of cathepsin K inhibition for the treatment and/or prophylaxis of pulmonary hypertension and/or heart failure |
CN103275070A (zh) * | 2013-05-10 | 2013-09-04 | 郑彪 | 调节单核细胞增殖的四环化合物及其应用 |
JP6336973B2 (ja) * | 2013-06-14 | 2018-06-06 | 生化学工業株式会社 | α−オキソアシルアミノカプロラクタム誘導体 |
JP6226437B2 (ja) * | 2013-06-14 | 2017-11-08 | 生化学工業株式会社 | α−オキソアシルアミノカプロラクタム体 |
BR112019004864A8 (pt) | 2016-09-16 | 2023-03-07 | Cortexyme Inc | Inibidores cetona de lisina gingipain |
WO2021191875A1 (en) | 2020-03-26 | 2021-09-30 | Glaxosmithkline Intellectual Property Development Limited | Cathepsin inhibitors for preventing or treating viral infections |
Family Cites Families (95)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4038247A (en) * | 1970-05-19 | 1977-07-26 | Ciba-Geigy Corporation | Stabilizing polyolefins with diacyl dihydrazides |
US5142056A (en) * | 1989-05-23 | 1992-08-25 | Abbott Laboratories | Retroviral protease inhibiting compounds |
US5057525A (en) * | 1981-10-01 | 1991-10-15 | Janssen Pharmaceutica N.V. | Novel N-(3-hydroxy-4-piperidinyl) benzamide derivatives |
IT1195287B (it) * | 1981-11-05 | 1988-10-12 | Ausonia Farma Srl | Derivato tiazolico,procedimento per la sua preparazione e relative composizioni farmaceutiche |
US4518528A (en) * | 1983-05-19 | 1985-05-21 | Rasnick David W | α Amino fluoro ketones |
US4749792A (en) * | 1984-09-26 | 1988-06-07 | E. R. Squibb & Sons, Inc. | Diamino ketones and alcohols as analgesic agents |
US4638101A (en) | 1985-01-02 | 1987-01-20 | General Electric Company | Compositions |
US4638010A (en) * | 1985-02-28 | 1987-01-20 | E. R. Squibb & Sons, Inc. | Ester substituted aminoalkanoylureido amino and imino acid and ester compounds |
JP2570686B2 (ja) | 1985-12-23 | 1997-01-08 | 日産化学工業株式会社 | ピラゾ−ル誘導体 |
DE3600288A1 (de) | 1986-01-08 | 1987-07-16 | Bayer Ag | Verwendung von amiden zur verbesserung der kulturpflanzen-vertraeglichkeit von herbizid wirksamen sulfonylharnstoff-derivaten |
KR900006545B1 (ko) | 1986-03-14 | 1990-09-13 | 신텍스(미합중국) 인코포레이티드 | 트란스글루타미나제 억제제 |
US5374637A (en) * | 1989-03-22 | 1994-12-20 | Janssen Pharmaceutica N.V. | N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or dihydrobenzodioxin)carboxamide derivatives |
US4994471A (en) * | 1989-05-12 | 1991-02-19 | Boc, Inc. | N-aryl-N-(1-substituted-3-alkoxy-4-piperidinyl)amides and pharmaceutical compositions and methods employing such compounds |
UA41251C2 (uk) | 1990-01-04 | 2001-09-17 | Пфайзер, Інк. | Гідровані азотвмісні гетероциклічні сполуки, похідні піперидину, фармацевтична композиція та спосіб пригнічення активності речовини р в організмі |
GB9019558D0 (en) | 1990-09-07 | 1990-10-24 | Szelke Michael | Enzyme inhibitors |
EP0504938A3 (en) | 1991-03-22 | 1993-04-14 | Suntory Limited | Prophylactic and therapeutic agent for bone diseases comprising di- or tripeptide derivative as active ingredient |
JP3190431B2 (ja) | 1991-07-01 | 2001-07-23 | 三菱化学株式会社 | ケトン誘導体 |
JPH05140063A (ja) * | 1991-11-19 | 1993-06-08 | Suntory Ltd | ジペプチド誘導体及びそれを有効成分とする骨疾患の予防及び治療剤 |
US5216168A (en) * | 1992-04-01 | 1993-06-01 | G. D. Searle & Co. | 2- and 3- amino and azido derivatives of 1,5-iminosugars |
US5206251A (en) * | 1992-04-01 | 1993-04-27 | G. D. Searle & Co. | 2- and 3- amino and azido derivatives of 1,5-iminosugars |
AU4544993A (en) | 1992-06-24 | 1994-01-24 | Cortex Pharmaceuticals, Inc. | Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity |
US5374623A (en) | 1992-08-20 | 1994-12-20 | Prototek, Inc. | Cysteine protease inhibitors effective for in vivo use |
CA2111930A1 (en) * | 1992-12-25 | 1994-06-26 | Ryoichi Ando | Aminoketone derivatives |
DK0603769T3 (da) * | 1992-12-25 | 1999-06-14 | Mitsubishi Chem Corp | Alfa-aminoketonderivater |
JPH06199850A (ja) * | 1992-12-28 | 1994-07-19 | Tanabe Seiyaku Co Ltd | インドール含有ペプチド及びその製法 |
JP2848232B2 (ja) | 1993-02-19 | 1999-01-20 | 武田薬品工業株式会社 | アルデヒド誘導体 |
EP0693124A1 (en) | 1993-04-06 | 1996-01-24 | Forsyth Dental Infirmary For Children | Human osteoclast-specific and -related genes |
TW494094B (en) | 1993-04-29 | 2002-07-11 | Vertex Pharma | Peptide analogs as irreversible interleukin-1β protease inhibitors and pharmaceutical compositions comprising the same |
AU7714594A (en) | 1993-08-13 | 1995-03-14 | Merck & Co., Inc. | Substituted ketone derivatives as inhibitors of interleukin-1beta converting enzyme |
US5501969A (en) | 1994-03-08 | 1996-03-26 | Human Genome Sciences, Inc. | Human osteoclast-derived cathepsin |
US5668128A (en) | 1994-04-13 | 1997-09-16 | Takeda Chemical Industries, Ltd. | Aziridine derivatives, their production and use |
US5585387A (en) | 1994-10-07 | 1996-12-17 | Torcan Chemical Ltd. | Prepration of cisapride |
US6544767B1 (en) | 1994-10-27 | 2003-04-08 | Axys Pharmaceuticals, Inc. | Cathespin O2 protease |
US5734977A (en) * | 1994-11-10 | 1998-03-31 | Telefonaktiebolaget Lm Ericsson | Fraud detection in radio communications network |
TW438591B (en) | 1995-06-07 | 2001-06-07 | Arris Pharm Corp | Reversible cysteine protease inhibitors |
SK88997A3 (en) | 1995-10-30 | 1998-05-06 | Smithkline Beecham Corp | Method of inhibiting cathepsin k |
EA199800353A1 (ru) | 1995-10-30 | 1998-12-24 | Смитклайн Бичам Корпорейшн | Ингибиторы протеаз |
US6083947A (en) * | 1996-01-29 | 2000-07-04 | The Regents Of The University Of California | Method for treating sexual dysfunctions |
US5902882A (en) | 1996-04-17 | 1999-05-11 | Hoffmann-La Roche Inc. | Assymetric synthesis of azepines |
WO1997049668A1 (en) | 1996-06-13 | 1997-12-31 | Smithkline Beecham Corporation | Inhibitiors of cysteine protease |
AU6333296A (en) | 1996-06-14 | 1998-01-07 | Human Genome Sciences, Inc. | Cathepsin k gene |
US5861298A (en) * | 1996-06-17 | 1999-01-19 | Smithkline Beecham Corporation | Cathepsin K gene |
DZ2285A1 (fr) | 1996-08-08 | 2002-12-25 | Smithkline Beecham Corp | Inhibiteurs de protéase de la cystéine. |
JP2000517319A (ja) | 1996-08-28 | 2000-12-26 | スミスクライン・ビーチャム・コーポレイション | システインプロテアーゼのインヒビター |
US5830850A (en) * | 1996-08-28 | 1998-11-03 | Mount Sinai School Of Medicine Of The City Of New York | Methods for the treatment of bone resorption disorders, including osteoporosis |
DE69717647T2 (de) | 1996-09-19 | 2003-09-25 | Aventis Pharmaceuticals Inc., Bridgewater | 3-mercaptoacetylamino-1,5-substituierte-2-oxo-azepan derivate und deren verwendung als inhibitoren von matrix-metalloproteinasen |
US5948669A (en) | 1997-02-26 | 1999-09-07 | Smithkline Beecham Corporation | Rat cathepsin K polynucleotide and polypeptide sequence |
AR012374A1 (es) | 1997-04-15 | 2000-10-18 | Smithkline Beecham Corp | Inhibidores de proteasas, composiones farmaceuticas y usos para la preparacion de medicamentos. |
JP2002501502A (ja) | 1997-04-25 | 2002-01-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害物質 |
MA26487A1 (fr) | 1997-04-29 | 2004-12-20 | Smithkline Beecham Corp | Heterocyclecetohydrazides inhibiteurs de proteases, procede pour leur preparation et compositions pharmaceutiques les contenant . |
US6566373B2 (en) * | 1997-05-06 | 2003-05-20 | Smithkline Beecham Corporation | Protease inhibitors |
EP0983228A4 (en) | 1997-05-08 | 2002-08-07 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
US6369077B1 (en) * | 1997-05-08 | 2002-04-09 | Smithkline Beecham Corporation | Protease inhibitors |
MA26540A1 (fr) | 1997-09-04 | 2004-12-20 | Smithkline Beecham Corp | Composes nouveaux inhibiteurs de proteases et compositions pharmaceutiques les contenant. |
MA26618A1 (fr) | 1998-04-09 | 2004-12-20 | Smithkline Beecham Corp | Composes et compositions pharmaceutiques pour le traitement du paludisme |
JP2002515428A (ja) | 1998-05-21 | 2002-05-28 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
MA26631A1 (fr) | 1998-05-21 | 2004-12-20 | Smithkline Beecham Corp | Composes a fonction bis-aminomethyl-carbonyle nouveaux, procede pour leur preparation et compositions pharmaceutiques les contenant |
DZ2815A1 (fr) | 1998-06-12 | 2003-12-01 | Smithkline Beecham Corp | Inhibiteurs de protéase. |
AR018915A1 (es) | 1998-06-24 | 2001-12-12 | Smithkline Beecham Corp | Inhibidores de proteasas diacilhidrazinicos, composicion farmaceutica que la comprenden, usos de los mismos para la manufactura de un medicamento, unprocedimiento de fabricacion de dichos compuestos |
WO2000009653A2 (en) | 1998-08-14 | 2000-02-24 | Smithkline Beecham Corporation | Method of inhibiting cathepsin k |
CO5150165A1 (es) | 1998-11-13 | 2002-04-29 | Smithkline Beecham Plc | Inhibidores de proteasa: tipo catepsina k |
US20030044399A1 (en) | 1998-12-23 | 2003-03-06 | Smithkline Beecham Corporation | Method of treatment |
CO5180541A1 (es) | 1998-12-23 | 2002-07-30 | Smithkline Beechman Corp | Inhibidores de proteasa del tipo de 1,3-diaminocetonas con anillo de 8-14 miembros |
HUP0104768A3 (en) * | 1998-12-23 | 2002-05-28 | Smithkline Beecham Corp | 4-amino-3-oxo-azepanes as protease inhibitors and pharmaceutical compositions containing the same |
JP2002536437A (ja) | 1999-02-09 | 2002-10-29 | ブリストル−マイヤーズ スクイブ カンパニー | FXaのラクタム抑制剤および方法 |
DZ3083A1 (fr) | 1999-02-19 | 2004-06-02 | Smithkline Beecham Corp | Composés nouveaux inhibiteurs de protéases, procédé pour leur préparation et compositions pharmaceutiques les conentant. |
UY26026A1 (es) | 1999-03-16 | 2000-10-31 | Smithkline Beecham Corportion | Inhibidores de proteasas |
UY26088A1 (es) | 1999-03-31 | 2000-10-31 | Smithkline Beecham Corp | Inhibidores de proteasas |
DE60041584D1 (de) | 1999-07-28 | 2009-04-02 | Aventis Pharma Inc | Substituierte oxoazaheterozyclische verbindungen |
JP2003513922A (ja) | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
WO2001034153A1 (en) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
EP1229914A4 (en) * | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
EP1235577A4 (en) | 1999-11-10 | 2003-04-09 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
EP1231922A4 (en) | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
WO2001034157A1 (en) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
JP2003513926A (ja) | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
WO2001034599A1 (en) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
AU1474601A (en) | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
JP2003533432A (ja) | 1999-11-10 | 2003-11-11 | スミスクライン・ビーチャム・コーポレイション | プロテア−ゼ阻害剤 |
WO2001034600A1 (en) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
JP2003513928A (ja) | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
DE10004572A1 (de) * | 2000-02-02 | 2001-08-09 | Boehringer Ingelheim Pharma | Neue positive allosterische AMPA-Rezeptor Modulatoren (PAARM), Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
NZ520588A (en) | 2000-03-21 | 2004-06-25 | Smithkline Beecham Corp | Protease inhibitors |
US20030114437A1 (en) | 2002-10-17 | 2003-06-19 | Cummings Maxwell D. | Protease inhibitors |
EP1320370A4 (en) | 2000-09-01 | 2008-10-22 | Smithkline Beecham Corp | TREATMENT METHOD |
HUP0301964A3 (en) | 2000-11-22 | 2007-09-28 | Smithkline Beecham Corp | Protease inhibitors |
US20040034013A1 (en) * | 2001-04-17 | 2004-02-19 | Cummings Maxwell D | Methods of treatment |
EP1401453A4 (en) | 2001-05-17 | 2005-04-06 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
WO2003026770A1 (en) | 2001-09-24 | 2003-04-03 | Smithkline Beecham Corporation | Method for removing metal from the products of olefin metathesis reactions |
AU2002360409A1 (en) | 2001-11-21 | 2003-06-10 | Smithkline Beecham Corporation | Methods and intermediates for the synthesis of azepines |
EP1534292A4 (en) | 2002-05-22 | 2008-04-02 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
US7109233B2 (en) | 2002-05-22 | 2006-09-19 | Smithkline Beecham Corporation | Protease inhibitors |
WO2003103574A2 (en) | 2002-05-22 | 2003-12-18 | Smithkline Beecham Corporation | Protease inhibitors |
EP1511745A4 (en) | 2002-05-22 | 2006-11-15 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
US7366462B2 (en) | 2003-10-24 | 2008-04-29 | Qualcomm Incorporated | Method and apparatus for seamlessly switching reception between multimedia streams in a wireless communication system |
-
2001
- 2001-03-07 NZ NZ520588A patent/NZ520588A/en unknown
- 2001-03-07 PL PL01357727A patent/PL357727A1/xx not_active Application Discontinuation
- 2001-03-07 SK SK1363-2002A patent/SK13632002A3/sk unknown
- 2001-03-07 HU HU0300068A patent/HUP0300068A2/hu unknown
- 2001-03-07 KR KR1020027012366A patent/KR20020082896A/ko active IP Right Grant
- 2001-03-07 US US10/239,343 patent/US7071184B2/en not_active Expired - Fee Related
- 2001-03-07 OA OA1200200295A patent/OA12323A/en unknown
- 2001-03-07 JP JP2001568430A patent/JP2003527429A/ja active Pending
- 2001-03-07 IL IL15096401A patent/IL150964A0/xx unknown
- 2001-03-07 AU AU4344101A patent/AU4344101A/xx active Pending
- 2001-03-07 CN CN01806446A patent/CN1416346A/zh active Pending
- 2001-03-07 WO PCT/US2001/007094 patent/WO2001070232A1/en active IP Right Grant
- 2001-03-07 CA CA002404206A patent/CA2404206A1/en not_active Abandoned
- 2001-03-07 AU AU2001243441A patent/AU2001243441B2/en not_active Ceased
- 2001-03-07 CZ CZ20023168A patent/CZ20023168A3/cs unknown
- 2001-03-07 EP EP01916412A patent/EP1307203A4/en not_active Withdrawn
- 2001-03-07 EA EA200201001A patent/EA005893B1/ru unknown
- 2001-03-07 BR BR0109356-8A patent/BR0109356A/pt not_active IP Right Cessation
- 2001-03-07 MX MXPA02009305A patent/MXPA02009305A/es active IP Right Grant
- 2001-03-07 DZ DZ013318A patent/DZ3318A1/fr active
- 2001-03-07 AP APAP/P/2002/002593A patent/AP1540A/en active
- 2001-03-19 UY UY26625A patent/UY26625A1/es not_active Application Discontinuation
- 2001-03-21 AR ARP010101323A patent/AR032877A1/es not_active Application Discontinuation
- 2001-03-21 PE PE2001000259A patent/PE20011233A1/es not_active Application Discontinuation
- 2001-03-21 MY MYPI20011339A patent/MY141596A/en unknown
-
2002
- 2002-07-29 BG BG106962A patent/BG106962A/bg unknown
- 2002-09-20 NO NO20024528A patent/NO20024528L/no not_active Application Discontinuation
-
2006
- 2006-04-25 US US11/410,558 patent/US7563784B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
BG106962A (bg) | 2003-03-31 |
IL150964A0 (en) | 2003-02-12 |
EA200201001A1 (ru) | 2003-02-27 |
CA2404206A1 (en) | 2001-09-27 |
JP2003527429A (ja) | 2003-09-16 |
US7563784B2 (en) | 2009-07-21 |
DZ3318A1 (fr) | 2001-09-27 |
US20040044201A1 (en) | 2004-03-04 |
EA005893B1 (ru) | 2005-06-30 |
OA12323A (en) | 2006-05-15 |
HUP0300068A2 (en) | 2003-05-28 |
WO2001070232A1 (en) | 2001-09-27 |
PE20011233A1 (es) | 2002-02-07 |
MY141596A (en) | 2010-05-31 |
CZ20023168A3 (cs) | 2003-02-12 |
CN1416346A (zh) | 2003-05-07 |
NO20024528D0 (no) | 2002-09-20 |
EP1307203A4 (en) | 2005-08-17 |
NO20024528L (no) | 2002-11-19 |
AP2002002593A0 (en) | 2002-09-30 |
US20060194787A1 (en) | 2006-08-31 |
EP1307203A1 (en) | 2003-05-07 |
US7071184B2 (en) | 2006-07-04 |
BR0109356A (pt) | 2003-06-03 |
AU2001243441B2 (en) | 2004-11-25 |
AU4344101A (en) | 2001-10-03 |
MXPA02009305A (es) | 2003-03-12 |
AR032877A1 (es) | 2003-12-03 |
KR20020082896A (ko) | 2002-10-31 |
AP1540A (en) | 2006-01-11 |
PL357727A1 (en) | 2004-07-26 |
NZ520588A (en) | 2004-06-25 |
UY26625A1 (es) | 2001-09-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2001243441B2 (en) | Protease inhibitors | |
AU2001243441A1 (en) | Protease inhibitors | |
US20030225061A1 (en) | Protease inhibitors | |
SK17592002A3 (sk) | 4-Amino-azepán-3-ónové zlúčeniny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom, ich použitie a medziprodukty | |
CZ20023460A3 (en) | Protease inhibitors | |
US20030114437A1 (en) | Protease inhibitors | |
EP1161237A1 (en) | Protease inhibitors | |
WO2003053331A2 (en) | Protease inhibitors | |
US20050256100A1 (en) | Protease inhibitors | |
EP1384713B1 (en) | 4-amino-azepan-3-one derivatives as protease inhibitors | |
US7109233B2 (en) | Protease inhibitors | |
US20040192674A1 (en) | Cathepsin L inhibitors | |
US20030044399A1 (en) | Method of treatment | |
US20040038965A1 (en) | Protease inhibitors | |
EP1511492A2 (en) | Protease inhibitors | |
ZA200207872B (en) | Protease inhibitors. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FB9A | Suspension of patent application procedure |