SK8102002A3 - Ox(adi)azolyl-hydroxamic acids useful as procollagen C-proteinase inhibitors - Google Patents

Info

Publication number

SK8102002A3

SK8102002A3 SK810-2002A SK8102002A SK8102002A3 SK 8102002 A3 SK8102002 A3 SK 8102002A3 SK 8102002 A SK8102002 A SK 8102002A SK 8102002 A3 SK8102002 A3 SK 8102002A3

Authority

SK

Slovakia

Prior art keywords

mmol

formula

compounds

compound

cyclohexyl

Prior art date

1999-12-23

Links

• Espacenet
• Global Dossier
• Discuss

• 102100028728 Bone morphogenetic protein 1 Human genes 0.000 title claims abstract description 51
• 108090000654 Bone morphogenetic protein 1 Proteins 0.000 title claims abstract description 51
• 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 title description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 235
• 150000003839 salts Chemical class 0.000 claims abstract description 55
• 229940002612 prodrug Drugs 0.000 claims abstract description 32
• 239000000651 prodrug Substances 0.000 claims abstract description 32
• 239000012453 solvate Substances 0.000 claims abstract description 29
• 239000003112 inhibitor Substances 0.000 claims abstract description 23
• 230000001404 mediated effect Effects 0.000 claims abstract description 7
• 238000000034 method Methods 0.000 claims description 235
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 116
• -1 phenylsulfonylmethyl Chemical group 0.000 claims description 79
• 229910052757 nitrogen Inorganic materials 0.000 claims description 76
• 238000002360 preparation method Methods 0.000 claims description 63
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 102100026802 72 kDa type IV collagenase Human genes 0.000 claims description 28
• 101710151806 72 kDa type IV collagenase Proteins 0.000 claims description 26
• 125000004432 carbon atom Chemical group C* 0.000 claims description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 claims description 20
• 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 claims description 20
• 108010015302 Matrix metalloproteinase-9 Proteins 0.000 claims description 19
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
• 239000001257 hydrogen Substances 0.000 claims description 19
• 102100030412 Matrix metalloproteinase-9 Human genes 0.000 claims description 18
• VVYVFZRWUJASEV-CQSZACIVSA-N (2r)-5-cyclohexyl-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pentanoic acid Chemical compound CC(C)(C)OC(=O)C[C@H](C(O)=O)CCCC1CCCCC1 VVYVFZRWUJASEV-CQSZACIVSA-N 0.000 claims description 17
• 102100030216 Matrix metalloproteinase-14 Human genes 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 14
• 239000000126 substance Substances 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 108010076557 Matrix Metalloproteinase 14 Proteins 0.000 claims description 13
• 230000008569 process Effects 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 11
• 125000001153 fluoro group Chemical group F* 0.000 claims description 11
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 10
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
• 238000011282 treatment Methods 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 239000001301 oxygen Chemical group 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
• 125000004429 atom Chemical group 0.000 claims description 5
• 238000009833 condensation Methods 0.000 claims description 5
• 230000005494 condensation Effects 0.000 claims description 5
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 229910052717 sulfur Chemical group 0.000 claims description 5
• 239000011593 sulfur Chemical group 0.000 claims description 5
• HZSBMUWLMGKWMN-SDNWHVSQSA-N (e)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-phenylpent-2-enoic acid Chemical compound CC(C)(C)OC(=O)C\C(C(O)=O)=C/CCC1=CC=CC=C1 HZSBMUWLMGKWMN-SDNWHVSQSA-N 0.000 claims description 4
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• ARJCBSRIPGJMAD-LLVKDONJSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carboxamide Chemical compound NC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 ARJCBSRIPGJMAD-LLVKDONJSA-N 0.000 claims description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• RDSMOKJZGFXQCT-IBGZPJMESA-N (4s)-4-benzyl-3-(5-cyclohexylpentanoyl)-1,3-oxazolidin-2-one Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)CCCCC1CCCCC1 RDSMOKJZGFXQCT-IBGZPJMESA-N 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• QZHKYOPXQSFVRT-UHFFFAOYSA-N 2-diethoxyphosphoryl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid Chemical compound CCOP(=O)(OCC)C(C(O)=O)CC(=O)OC(C)(C)C QZHKYOPXQSFVRT-UHFFFAOYSA-N 0.000 claims description 3
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
• 239000002671 adjuvant Substances 0.000 claims description 3
• 125000004450 alkenylene group Chemical group 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 3
• 150000004677 hydrates Chemical class 0.000 claims description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• OIXMXOATOMTGIL-GFCCVEGCSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-methyl-1,2,4-oxadiazole-3-carboxamide Chemical compound CNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 OIXMXOATOMTGIL-GFCCVEGCSA-N 0.000 claims description 2
• VVYVFZRWUJASEV-UHFFFAOYSA-N 5-cyclohexyl-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pentanoic acid Chemical compound CC(C)(C)OC(=O)CC(C(O)=O)CCCC1CCCCC1 VVYVFZRWUJASEV-UHFFFAOYSA-N 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 150000001204 N-oxides Chemical class 0.000 claims description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical group C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims description 2
• 150000001721 carbon Chemical group 0.000 claims description 2
• 125000004122 cyclic group Chemical group 0.000 claims description 2
• 150000003946 cyclohexylamines Chemical class 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• 125000002950 monocyclic group Chemical group 0.000 claims description 2
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 2
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000006413 ring segment Chemical group 0.000 claims description 2
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
• ARKLZNKRUULBKN-WCSIJFPASA-N tert-butyl 3-[(4s)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]-6-cyclohexylhexanoate Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)C(CC(=O)OC(C)(C)C)CCCC1CCCCC1 ARKLZNKRUULBKN-WCSIJFPASA-N 0.000 claims description 2
• FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 claims 1
• FRASWKFJOBLAQF-CYBMUJFWSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n,n-dimethyl-1,2,4-oxadiazole-3-carboxamide Chemical compound CN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 FRASWKFJOBLAQF-CYBMUJFWSA-N 0.000 claims 1
• 230000003213 activating effect Effects 0.000 claims 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 685
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 539
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 398
• 239000000203 mixture Substances 0.000 description 292
• 239000000243 solution Substances 0.000 description 272
• 230000002829 reductive effect Effects 0.000 description 240
• 239000002904 solvent Substances 0.000 description 230
• 235000019439 ethyl acetate Nutrition 0.000 description 181
• 238000005160 1H NMR spectroscopy Methods 0.000 description 160
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 132
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 132
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 106
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 103
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 96
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 89
• 238000004440 column chromatography Methods 0.000 description 74
• 239000007787 solid Substances 0.000 description 72
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 69
• 239000012267 brine Substances 0.000 description 64
• 239000012299 nitrogen atmosphere Substances 0.000 description 64
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 64
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 63
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 62
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 59
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 57
• 239000000741 silica gel Substances 0.000 description 56
• 229910002027 silica gel Inorganic materials 0.000 description 56
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 54
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
• 239000003921 oil Substances 0.000 description 44
• 235000019198 oils Nutrition 0.000 description 44
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 44
• 239000012044 organic layer Substances 0.000 description 42
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
• 239000012230 colorless oil Substances 0.000 description 39
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
• 229910021529 ammonia Inorganic materials 0.000 description 34
• 108010035532 Collagen Proteins 0.000 description 33
• 102000008186 Collagen Human genes 0.000 description 33
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
• 238000004458 analytical method Methods 0.000 description 33
• 239000010410 layer Substances 0.000 description 33
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 32
• 229920001436 collagen Polymers 0.000 description 32
• AEKHNNJSMVVESS-UHFFFAOYSA-N o-trimethylsilylhydroxylamine Chemical compound C[Si](C)(C)ON AEKHNNJSMVVESS-UHFFFAOYSA-N 0.000 description 32
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 239000003480 eluent Substances 0.000 description 29
• 238000010828 elution Methods 0.000 description 28
• 102000004190 Enzymes Human genes 0.000 description 25
• 108090000790 Enzymes Proteins 0.000 description 25
• 229940088598 enzyme Drugs 0.000 description 25
• 238000010898 silica gel chromatography Methods 0.000 description 25
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 23
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
• 239000002253 acid Substances 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• 229920006395 saturated elastomer Polymers 0.000 description 21
• 229960000583 acetic acid Drugs 0.000 description 20
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 20
• 238000004128 high performance liquid chromatography Methods 0.000 description 20
• 239000000725 suspension Substances 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 18
• ZKEOPGBLILZRRC-MRXNPFEDSA-N ethyl 5-[(3r)-6-cyclohexyl-1-[(2-methylpropan-2-yl)oxy]-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carboxylate Chemical compound CCOC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 ZKEOPGBLILZRRC-MRXNPFEDSA-N 0.000 description 17
• 239000006260 foam Substances 0.000 description 17
• 230000005764 inhibitory process Effects 0.000 description 17
• 239000012074 organic phase Substances 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
• 238000003556 assay Methods 0.000 description 16
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
• 239000000758 substrate Substances 0.000 description 16
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 15
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• 239000003153 chemical reaction reagent Substances 0.000 description 14
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 14
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 13
• YIHVTLUDAYABNF-CYBMUJFWSA-N (3r)-6-cyclohexyl-3-(3-ethoxycarbonyl-1,2,4-oxadiazol-5-yl)hexanoic acid Chemical compound CCOC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 YIHVTLUDAYABNF-CYBMUJFWSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
• 230000000694 effects Effects 0.000 description 12
• 239000011780 sodium chloride Substances 0.000 description 12
• 238000010511 deprotection reaction Methods 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• 201000004624 Dermatitis Diseases 0.000 description 10
• 206010016654 Fibrosis Diseases 0.000 description 10
• 230000004761 fibrosis Effects 0.000 description 10
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 238000004587 chromatography analysis Methods 0.000 description 9
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• 239000008346 aqueous phase Substances 0.000 description 8
• 238000003776 cleavage reaction Methods 0.000 description 8
• 230000000875 corresponding effect Effects 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
• 230000007017 scission Effects 0.000 description 8
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 7
• 108010010803 Gelatin Proteins 0.000 description 7
• 208000027418 Wounds and injury Diseases 0.000 description 7
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 7
• 229920000159 gelatin Polymers 0.000 description 7
• 235000019322 gelatine Nutrition 0.000 description 7
• 235000011852 gelatine desserts Nutrition 0.000 description 7
• 238000005984 hydrogenation reaction Methods 0.000 description 7
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 7
• 229910000029 sodium carbonate Inorganic materials 0.000 description 7
• 239000008096 xylene Substances 0.000 description 7
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 108010050808 Procollagen Proteins 0.000 description 6
• 206010052428 Wound Diseases 0.000 description 6
• 235000019270 ammonium chloride Nutrition 0.000 description 6
• 239000012131 assay buffer Substances 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 239000002480 mineral oil Substances 0.000 description 6
• 235000010446 mineral oil Nutrition 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
• 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 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 230000037319 collagen production Effects 0.000 description 5
• 230000008021 deposition Effects 0.000 description 5
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 230000037390 scarring Effects 0.000 description 5
• 210000003491 skin Anatomy 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 239000012312 sodium hydride Substances 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• MUWWBHGGDKKGBQ-LJQANCHMSA-N (3r)-3-[3-[3-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]azetidine-1-carbonyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid Chemical compound C1C(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)CN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 MUWWBHGGDKKGBQ-LJQANCHMSA-N 0.000 description 4
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 4
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 4
• 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 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
• 102000016359 Fibronectins Human genes 0.000 description 4
• 108010067306 Fibronectins Proteins 0.000 description 4
• 241000287828 Gallus gallus Species 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• 238000005481 NMR spectroscopy Methods 0.000 description 4
• 239000007983 Tris buffer Substances 0.000 description 4
• YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 4
• 239000001110 calcium chloride Substances 0.000 description 4
• 229910001628 calcium chloride Inorganic materials 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 235000013330 chicken meat Nutrition 0.000 description 4
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
• 210000002950 fibroblast Anatomy 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 239000011521 glass Substances 0.000 description 4
• VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 235000019341 magnesium sulphate Nutrition 0.000 description 4
• 238000002844 melting Methods 0.000 description 4
• 230000008018 melting Effects 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 239000003444 phase transfer catalyst Substances 0.000 description 4
• 231100000241 scar Toxicity 0.000 description 4
• 238000001179 sorption measurement Methods 0.000 description 4
• 239000011550 stock solution Substances 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• CTPSCNDCIYPIQP-OAHLLOKOSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(CO)N=1)CCC1CCCCC1 CTPSCNDCIYPIQP-OAHLLOKOSA-N 0.000 description 4
• 230000009466 transformation Effects 0.000 description 4
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
• 230000029663 wound healing Effects 0.000 description 4
• BLLMQOGLBBYQOS-CQSZACIVSA-N (2r)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-phenylpentanoic acid Chemical compound CC(C)(C)OC(=O)C[C@H](C(O)=O)CCCC1=CC=CC=C1 BLLMQOGLBBYQOS-CQSZACIVSA-N 0.000 description 3
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 102000016942 Elastin Human genes 0.000 description 3
• 108010014258 Elastin Proteins 0.000 description 3
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
• 101000695352 Homo sapiens Bone morphogenetic protein 1 Proteins 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 102000035195 Peptidases Human genes 0.000 description 3
• 108091005804 Peptidases Proteins 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
• 229940024606 amino acid Drugs 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
• XFILPEOLDIKJHX-QYZOEREBSA-N batimastat Chemical compound C([C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)[C@H](CSC=1SC=CC=1)C(=O)NO)C1=CC=CC=C1 XFILPEOLDIKJHX-QYZOEREBSA-N 0.000 description 3
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 3
• 238000004090 dissolution Methods 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000007850 fluorescent dye Substances 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 150000002431 hydrogen Chemical class 0.000 description 3
• 150000002443 hydroxylamines Chemical class 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 210000002510 keratinocyte Anatomy 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• 230000035800 maturation Effects 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• 239000002243 precursor Substances 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 239000011347 resin Substances 0.000 description 3
• 229920005989 resin Polymers 0.000 description 3
• 239000001509 sodium citrate Substances 0.000 description 3
• 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 3
• LVXMHFHCVZTXGS-OAHLLOKOSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(methylcarbamoyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound CNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 LVXMHFHCVZTXGS-OAHLLOKOSA-N 0.000 description 3
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• 239000011701 zinc Substances 0.000 description 3
• UJCKOKXASDHNIX-LLVKDONJSA-N (3r)-3-(3-carbamoyl-1,2,4-oxadiazol-5-yl)-6-cyclohexylhexanoic acid Chemical compound NC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 UJCKOKXASDHNIX-LLVKDONJSA-N 0.000 description 2
• SGCJQVSMYHQEIZ-QGZVFWFLSA-N (3r)-3-[3-(benzenesulfonylmethyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(CS(=O)(=O)C=2C=CC=CC=2)N=1)CCC1CCCCC1 SGCJQVSMYHQEIZ-QGZVFWFLSA-N 0.000 description 2
• ULKHTRFYTVSHSY-CYBMUJFWSA-N (3r)-3-[3-[(2-amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid Chemical compound NC(=O)COCC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 ULKHTRFYTVSHSY-CYBMUJFWSA-N 0.000 description 2
• YUGBCMVRZXFYQV-MRXNPFEDSA-N (3r)-3-[3-[(4-chlorophenoxy)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(COC=2C=CC(Cl)=CC=2)N=1)CCC1CCCCC1 YUGBCMVRZXFYQV-MRXNPFEDSA-N 0.000 description 2
• BGZGOASLLMMFDR-CYBMUJFWSA-N (3r)-6-cyclohexyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)hexanoic acid Chemical compound CC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 BGZGOASLLMMFDR-CYBMUJFWSA-N 0.000 description 2
• PYGBDQBGDBNTES-CQSZACIVSA-N (3r)-6-cyclohexyl-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)hexanoic acid Chemical compound CC(C)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 PYGBDQBGDBNTES-CQSZACIVSA-N 0.000 description 2
• SIWQBFJEYIHVTQ-PFEQFJNWSA-N (3r)-6-cyclohexyl-3-(4-ethoxycarbonyl-1,3-oxazol-2-yl)hexanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)C1=COC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 SIWQBFJEYIHVTQ-PFEQFJNWSA-N 0.000 description 2
• CWICMJKRSKCHAL-CQSZACIVSA-N (3r)-6-cyclohexyl-3-(4-methoxycarbonyl-5-methyl-1,3-oxazol-2-yl)hexanoic acid Chemical compound O1C(C)=C(C(=O)OC)N=C1[C@@H](CC(O)=O)CCCC1CCCCC1 CWICMJKRSKCHAL-CQSZACIVSA-N 0.000 description 2
• NOQVSUKPYFORPR-CQSZACIVSA-N (3r)-6-cyclohexyl-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound COCCC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 NOQVSUKPYFORPR-CQSZACIVSA-N 0.000 description 2
• NWBMOIVPVQYFSF-MRXNPFEDSA-N (3r)-6-cyclohexyl-3-[3-(2-oxo-2-pyrrolidin-1-ylethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(CC(=O)N2CCCC2)N=1)CCC1CCCCC1 NWBMOIVPVQYFSF-MRXNPFEDSA-N 0.000 description 2
• KYSZCPIIZSLWNE-OAHLLOKOSA-N (3r)-6-cyclohexyl-3-[3-(3-ethoxy-3-oxopropyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CCOC(=O)CCC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 KYSZCPIIZSLWNE-OAHLLOKOSA-N 0.000 description 2
• RMEIUKFTLOAIRT-UNTBIKODSA-N (3r)-6-cyclohexyl-3-[3-(3-morpholin-4-ylazetidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)N1CC(C1)N1CCOCC1)CCC1CCCCC1 RMEIUKFTLOAIRT-UNTBIKODSA-N 0.000 description 2
• QEXKSBJLYJUMBG-OAQYLSRUSA-N (3r)-6-cyclohexyl-3-[3-(4-pyridin-4-ylpiperidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)N1CCC(CC1)C=1C=CN=CC=1)CCC1CCCCC1 QEXKSBJLYJUMBG-OAQYLSRUSA-N 0.000 description 2
• WRAQPWAHJJHADN-CYBMUJFWSA-N (3r)-6-cyclohexyl-3-[3-(dimethylcarbamoyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 WRAQPWAHJJHADN-CYBMUJFWSA-N 0.000 description 2
• BUKRZBSVQDGKDD-CYBMUJFWSA-N (3r)-6-cyclohexyl-3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound COCC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 BUKRZBSVQDGKDD-CYBMUJFWSA-N 0.000 description 2
• ZAICXQBPUHIWOL-CQSZACIVSA-N (3r)-6-cyclohexyl-3-[3-(propylcarbamoyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CCCNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 ZAICXQBPUHIWOL-CQSZACIVSA-N 0.000 description 2
• AEMBODTXWUJYGQ-PKLMIRHRSA-N (3r)-6-cyclohexyl-3-[3-(pyridin-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](CC(=O)O)C=1ON=C(CC=2N=CC=CC=2)N=1)CCC1CCCCC1 AEMBODTXWUJYGQ-PKLMIRHRSA-N 0.000 description 2
• JIWBVUBVFYQURB-OAHLLOKOSA-N (3r)-6-cyclohexyl-3-[3-(pyrrolidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)N1CCCC1)CCC1CCCCC1 JIWBVUBVFYQURB-OAHLLOKOSA-N 0.000 description 2
• HLKROEAHEONJJT-BZSJEYESSA-N (3r)-6-cyclohexyl-3-[3-[(1-ethoxy-1-oxopropan-2-yl)oxymethyl]-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CCOC(=O)C(C)OCC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 HLKROEAHEONJJT-BZSJEYESSA-N 0.000 description 2
• YCSUZPHOLUGNFE-CQSZACIVSA-N (3r)-6-cyclohexyl-3-[3-[(2-methoxy-2-oxoethyl)-methylcarbamoyl]-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound COC(=O)CN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 YCSUZPHOLUGNFE-CQSZACIVSA-N 0.000 description 2
• RGJRTZHCNPJUCR-OAHLLOKOSA-N (3r)-6-cyclohexyl-3-[3-[3-(dimethylamino)azetidine-1-carbonyl]-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C1C(N(C)C)CN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 RGJRTZHCNPJUCR-OAHLLOKOSA-N 0.000 description 2
• CIQMTPRJFBPVCZ-UNTBIKODSA-N (3r)-6-cyclohexyl-3-[3-[4-(dimethylamino)piperidine-1-carbonyl]-1,2,4-oxadiazol-5-yl]hexanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CC(N(C)C)CCN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 CIQMTPRJFBPVCZ-UNTBIKODSA-N 0.000 description 2
• BTZREJFYIYLWCQ-MRXNPFEDSA-N (3r)-6-cyclohexyl-3-[3-[[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]carbamoyl]-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C1N(C(=O)OC(C)(C)C)CC1NC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 BTZREJFYIYLWCQ-MRXNPFEDSA-N 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
• HZUQQPZFKAMWEP-MRXNPFEDSA-N 1-o-[(e)-(1-amino-2-ethoxy-2-oxoethylidene)amino] 4-o-tert-butyl (2r)-2-(3-cyclohexylpropyl)butanedioate Chemical compound CCOC(=O)C(\N)=N\OC(=O)[C@@H](CC(=O)OC(C)(C)C)CCCC1CCCCC1 HZUQQPZFKAMWEP-MRXNPFEDSA-N 0.000 description 2
• VCXSFAGCDRTRHA-GOSISDBHSA-N 1-o-[(e)-(1-amino-2-propylsulfonylethylidene)amino] 4-o-tert-butyl (2r)-2-(3-cyclohexylpropyl)butanedioate Chemical compound CCCS(=O)(=O)C\C(N)=N\OC(=O)[C@@H](CC(=O)OC(C)(C)C)CCCC1CCCCC1 VCXSFAGCDRTRHA-GOSISDBHSA-N 0.000 description 2
• TYZFDEBMMDXLCU-LJQANCHMSA-N 2-[(3r)-6-cyclohexyl-1-oxo-1-(phenylmethoxyamino)hexan-3-yl]-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC([C@H](CCCC2CCCCC2)CC(=O)NOCC=2C=CC=CC=2)=N1 TYZFDEBMMDXLCU-LJQANCHMSA-N 0.000 description 2
• PNPZGVVMLGJCOQ-HXUWFJFHSA-N 2-[(3r)-6-cyclohexyl-1-oxo-1-(phenylmethoxyamino)hexan-3-yl]-5-methyl-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)OC([C@H](CCCC2CCCCC2)CC(=O)NOCC=2C=CC=CC=2)=N1 PNPZGVVMLGJCOQ-HXUWFJFHSA-N 0.000 description 2
• ZZVLLWWKBXGGHX-JOCHJYFZSA-N 2-[(3r)-6-cyclohexyl-1-oxo-1-(phenylmethoxyamino)hexan-3-yl]-n,n,5-trimethyl-1,3-oxazole-4-carboxamide Chemical compound O1C(C)=C(C(=O)N(C)C)N=C1[C@@H](CC(=O)NOCC=1C=CC=CC=1)CCCC1CCCCC1 ZZVLLWWKBXGGHX-JOCHJYFZSA-N 0.000 description 2
• RGBWBVGQZFJTEO-UHFFFAOYSA-N 4-piperidin-4-ylpyridine Chemical compound C1CNCCC1C1=CC=NC=C1 RGBWBVGQZFJTEO-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• YMUHUYBRWUUAJF-UHFFFAOYSA-N 5-cyclohexylpentanoic acid Chemical compound OC(=O)CCCCC1CCCCC1 YMUHUYBRWUUAJF-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
• 108010022452 Collagen Type I Proteins 0.000 description 2
• 102000012422 Collagen Type I Human genes 0.000 description 2
• 102100027995 Collagenase 3 Human genes 0.000 description 2
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 206010023421 Kidney fibrosis Diseases 0.000 description 2
• 102000007547 Laminin Human genes 0.000 description 2
• 108010085895 Laminin Proteins 0.000 description 2
• 229940124761 MMP inhibitor Drugs 0.000 description 2
• 102000005741 Metalloproteases Human genes 0.000 description 2
• 108010006035 Metalloproteases Proteins 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 101000695353 Mus musculus Bone morphogenetic protein 1 Proteins 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• 102000016611 Proteoglycans Human genes 0.000 description 2
• 108010067787 Proteoglycans Proteins 0.000 description 2
• 206010039710 Scleroderma Diseases 0.000 description 2
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
• 102100030416 Stromelysin-1 Human genes 0.000 description 2
• 102000004142 Trypsin Human genes 0.000 description 2
• 108090000631 Trypsin Proteins 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000012062 aqueous buffer Substances 0.000 description 2
• 239000003125 aqueous solvent Substances 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• 210000004899 c-terminal region Anatomy 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 238000004296 chiral HPLC Methods 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 208000018631 connective tissue disease Diseases 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
• 238000003869 coulometry Methods 0.000 description 2
• 239000007822 coupling agent Substances 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 2
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 210000001198 duodenum Anatomy 0.000 description 2
• 229920002549 elastin Polymers 0.000 description 2
• 239000012156 elution solvent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• BKBAQHIHGCAHQN-QGZVFWFLSA-N ethyl 2-[(3r)-6-cyclohexyl-1-[(2-methylpropan-2-yl)oxy]-1-oxohexan-3-yl]-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 BKBAQHIHGCAHQN-QGZVFWFLSA-N 0.000 description 2
• BTUVEWHOOYLGEV-OAQYLSRUSA-N ethyl 2-[(3r)-6-cyclohexyl-1-oxo-1-(phenylmethoxyamino)hexan-3-yl]-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC([C@H](CCCC2CCCCC2)CC(=O)NOCC=2C=CC=CC=2)=N1 BTUVEWHOOYLGEV-OAQYLSRUSA-N 0.000 description 2
• 230000005284 excitation Effects 0.000 description 2
• 210000002744 extracellular matrix Anatomy 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 239000000835 fiber Substances 0.000 description 2
• 230000003176 fibrotic effect Effects 0.000 description 2
• 238000001640 fractional crystallisation Methods 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 235000010299 hexamethylene tetramine Nutrition 0.000 description 2
• 239000004312 hexamethylene tetramine Substances 0.000 description 2
• 239000000017 hydrogel Substances 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 238000002329 infrared spectrum Methods 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
• 229940011051 isopropyl acetate Drugs 0.000 description 2
• 230000000155 isotopic effect Effects 0.000 description 2
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• LDORXNOIOSGZCL-OAQYLSRUSA-N methyl 2-[(3r)-6-cyclohexyl-1-oxo-1-(phenylmethoxyamino)hexan-3-yl]-5-methyl-1,3-oxazole-4-carboxylate Chemical compound O1C(C)=C(C(=O)OC)N=C1[C@@H](CC(=O)NOCC=1C=CC=CC=1)CCCC1CCCCC1 LDORXNOIOSGZCL-OAQYLSRUSA-N 0.000 description 2
• 238000013508 migration Methods 0.000 description 2
• 230000005012 migration Effects 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 238000012261 overproduction Methods 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 235000019271 petrolatum Nutrition 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 229920000058 polyacrylate Polymers 0.000 description 2
• FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
• 235000019833 protease Nutrition 0.000 description 2
• 238000007634 remodeling Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000037387 scars Effects 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 210000002435 tendon Anatomy 0.000 description 2
• SUAUQRDXVZHKAW-CQSZACIVSA-N tert-butyl (3r)-3-(3-carbamoyl-1,2,4-oxadiazol-5-yl)-6-phenylhexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(N)=O)CCC1=CC=CC=C1 SUAUQRDXVZHKAW-CQSZACIVSA-N 0.000 description 2
• VOAQHSOPRAAQAX-HXUWFJFHSA-N tert-butyl (3r)-3-[3-(benzenesulfonylmethyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(CS(=O)(=O)C=2C=CC=CC=2)N=1)CCC1CCCCC1 VOAQHSOPRAAQAX-HXUWFJFHSA-N 0.000 description 2
• XSBNONOIKUOHSH-OAQYLSRUSA-N tert-butyl (3r)-3-[3-(benzylcarbamoyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)NCC=1C=CC=CC=1)CCC1CCCCC1 XSBNONOIKUOHSH-OAQYLSRUSA-N 0.000 description 2
• HPMLSDCBEXELQC-MRXNPFEDSA-N tert-butyl (3r)-3-[3-[(2-amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(COCC(N)=O)N=1)CCC1CCCCC1 HPMLSDCBEXELQC-MRXNPFEDSA-N 0.000 description 2
• KAXWGYLXEDOOGP-LJQANCHMSA-N tert-butyl (3r)-3-[3-[(4-chlorophenoxy)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(COC=2C=CC(Cl)=CC=2)N=1)CCC1CCCCC1 KAXWGYLXEDOOGP-LJQANCHMSA-N 0.000 description 2
• SFMOJBHESQGJDY-JOCHJYFZSA-N tert-butyl (3r)-3-[3-[benzyl(methyl)carbamoyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate Chemical compound N=1OC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=NC=1C(=O)N(C)CC1=CC=CC=C1 SFMOJBHESQGJDY-JOCHJYFZSA-N 0.000 description 2
• GCDONZJOJYKZJT-QGZVFWFLSA-N tert-butyl (3r)-6-cyclohexyl-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)hexanoate Chemical compound CC(C)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 GCDONZJOJYKZJT-QGZVFWFLSA-N 0.000 description 2
• IXLGMWITNXDOIE-URSIVYNOSA-N tert-butyl (3r)-6-cyclohexyl-3-[(3-hydroxy-1-methoxy-1-oxobutan-2-yl)carbamoyl]hexanoate Chemical compound COC(=O)C(C(C)O)NC(=O)[C@@H](CC(=O)OC(C)(C)C)CCCC1CCCCC1 IXLGMWITNXDOIE-URSIVYNOSA-N 0.000 description 2
• BYBLERBGNNRZLU-HXUWFJFHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(1,3-dihydroisoindole-2-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CC2=CC=CC=C2C1)CCC1CCCCC1 BYBLERBGNNRZLU-HXUWFJFHSA-N 0.000 description 2
• ZLNUNUAUVHZSIQ-LJQANCHMSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(2-oxo-2-pyrrolidin-1-ylethyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(CC(=O)N2CCCC2)N=1)CCC1CCCCC1 ZLNUNUAUVHZSIQ-LJQANCHMSA-N 0.000 description 2
• JCJKRBMCGHWYTC-HXUWFJFHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(3-morpholin-4-ylazetidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CC(C1)N1CCOCC1)CCC1CCCCC1 JCJKRBMCGHWYTC-HXUWFJFHSA-N 0.000 description 2
• JIOHYTAMKMDJSQ-LJQANCHMSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(4-methylpiperazine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C1CN(C)CCN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 JIOHYTAMKMDJSQ-LJQANCHMSA-N 0.000 description 2
• GYDHQLYCVRIFHZ-XMMPIXPASA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(4-pyridin-4-ylpiperidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CCC(CC1)C=1C=CN=CC=1)CCC1CCCCC1 GYDHQLYCVRIFHZ-XMMPIXPASA-N 0.000 description 2
• QSXZZKUXYYNJKF-MRXNPFEDSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(dimethylcarbamoyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound CN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 QSXZZKUXYYNJKF-MRXNPFEDSA-N 0.000 description 2
• GKPGPMJXAATINV-MRXNPFEDSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound COCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 GKPGPMJXAATINV-MRXNPFEDSA-N 0.000 description 2
• NLRLAFHLUKIMLP-GOSISDBHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(morpholine-4-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CCOCC1)CCC1CCCCC1 NLRLAFHLUKIMLP-GOSISDBHSA-N 0.000 description 2
• XELRZQFCFKFLKJ-LJQANCHMSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(piperidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CCCCC1)CCC1CCCCC1 XELRZQFCFKFLKJ-LJQANCHMSA-N 0.000 description 2
• GZJVECJVLFAPMV-LJQANCHMSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(pyridin-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(CC=2N=CC=CC=2)N=1)CCC1CCCCC1 GZJVECJVLFAPMV-LJQANCHMSA-N 0.000 description 2
• WYLMYLZSZNLKEQ-GOSISDBHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(pyrrolidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CCCC1)CCC1CCCCC1 WYLMYLZSZNLKEQ-GOSISDBHSA-N 0.000 description 2
• SACDIZZIFLDDED-GOSISDBHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[(2-ethoxy-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound CCOC(=O)COCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 SACDIZZIFLDDED-GOSISDBHSA-N 0.000 description 2
• ONSSDQABZWIRDO-QGZVFWFLSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[(2-methoxy-2-oxoethyl)-methylcarbamoyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound COC(=O)CN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 ONSSDQABZWIRDO-QGZVFWFLSA-N 0.000 description 2
• UGKOJCIGVJWMQX-MRXNPFEDSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[(2-methoxy-2-oxoethyl)carbamoyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound COC(=O)CNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 UGKOJCIGVJWMQX-MRXNPFEDSA-N 0.000 description 2
• BYQFIRMRFHCUEV-LJQANCHMSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[2-(dimethylamino)ethyl-methylcarbamoyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound CN(C)CCN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 BYQFIRMRFHCUEV-LJQANCHMSA-N 0.000 description 2
• FZVHUEIBKHJIBS-GOSISDBHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[3-(dimethylamino)azetidine-1-carbonyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C1C(N(C)C)CN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 FZVHUEIBKHJIBS-GOSISDBHSA-N 0.000 description 2
• KBJCEYMEJDDPIO-HXUWFJFHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[3-(dimethylamino)propyl-methylcarbamoyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound CN(C)CCCN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 KBJCEYMEJDDPIO-HXUWFJFHSA-N 0.000 description 2
• ZTCRVAUENLQLLE-HXUWFJFHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[methyl(pyridin-2-ylmethyl)carbamoyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound N=1OC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=NC=1C(=O)N(C)CC1=CC=CC=N1 ZTCRVAUENLQLLE-HXUWFJFHSA-N 0.000 description 2
• PVEXZPMDTLUWNA-MSOLQXFVSA-N tert-butyl (3r)-6-cyclohexyl-3-[[(2s)-1-ethoxy-3-hydroxy-1-oxopropan-2-yl]carbamoyl]hexanoate Chemical compound CCOC(=O)[C@H](CO)NC(=O)[C@@H](CC(=O)OC(C)(C)C)CCCC1CCCCC1 PVEXZPMDTLUWNA-MSOLQXFVSA-N 0.000 description 2
• FNIHWOMOGHSTAT-UHFFFAOYSA-N tert-butyl 3-(1,3-dioxoisoindol-2-yl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1C(=O)C2=CC=CC=C2C1=O FNIHWOMOGHSTAT-UHFFFAOYSA-N 0.000 description 2
• WPGLRFGDZJSQGI-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)C1 WPGLRFGDZJSQGI-UHFFFAOYSA-N 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 125000005389 trialkylsiloxy group Chemical group 0.000 description 2
• 125000004665 trialkylsilyl group Chemical group 0.000 description 2
• GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 2
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 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 2
• 239000012588 trypsin Substances 0.000 description 2
• 239000004034 viscosity adjusting agent Substances 0.000 description 2
• 230000004580 weight loss Effects 0.000 description 2
• 229910052725 zinc Inorganic materials 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• GUEHESDOJBMSSE-UHFFFAOYSA-M (2-aminophenyl)mercury(1+);acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1N GUEHESDOJBMSSE-UHFFFAOYSA-M 0.000 description 1
• PXJACNDVRNAFHD-UHFFFAOYSA-N (2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1CN PXJACNDVRNAFHD-UHFFFAOYSA-N 0.000 description 1
• MRXDGVXSWIXTQL-HYHFHBMOSA-N (2s)-2-[[(1s)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2s)-4-methyl-1-oxo-1-[[(2s)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)C1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-HYHFHBMOSA-N 0.000 description 1
• TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 description 1
• QFYCIUPWJDUQHZ-CYBMUJFWSA-N (3r)-3-[3-(3-aminoazetidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexyl-n-hydroxyhexanamide Chemical compound C1C(N)CN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 QFYCIUPWJDUQHZ-CYBMUJFWSA-N 0.000 description 1
• YAUALZKWXPNKRN-GOSISDBHSA-N (3r)-3-[3-(benzylcarbamoyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)NCC=1C=CC=CC=1)CCC1CCCCC1 YAUALZKWXPNKRN-GOSISDBHSA-N 0.000 description 1
• MKDYKXKYZKDIHB-CYBMUJFWSA-N (3r)-3-[3-[(2-amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexyl-n-hydroxyhexanamide Chemical compound NC(=O)COCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 MKDYKXKYZKDIHB-CYBMUJFWSA-N 0.000 description 1
• IBBROOGTTCDKLH-MRXNPFEDSA-N (3r)-3-[3-[(4-chlorophenoxy)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexyl-n-hydroxyhexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(COC=2C=CC(Cl)=CC=2)N=1)CCC1CCCCC1 IBBROOGTTCDKLH-MRXNPFEDSA-N 0.000 description 1
• CNSDVEMXOIQNOC-LJQANCHMSA-N (3r)-3-[3-[benzyl(methyl)carbamoyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid Chemical compound N=1OC([C@H](CCCC2CCCCC2)CC(O)=O)=NC=1C(=O)N(C)CC1=CC=CC=C1 CNSDVEMXOIQNOC-LJQANCHMSA-N 0.000 description 1
• PPXXXQGSGUHEDC-GFCCVEGCSA-N (3r)-6-cyclobutyl-3-[4-(dimethylcarbamoyl)-1,3-oxazol-2-yl]hexanoic acid Chemical compound CN(C)C(=O)C1=COC([C@H](CCCC2CCC2)CC(O)=O)=N1 PPXXXQGSGUHEDC-GFCCVEGCSA-N 0.000 description 1
• FJWCNSHQAJTXOJ-CQSZACIVSA-N (3r)-6-cyclohexyl-3-(4-ethoxycarbonyl-1,3-oxazol-2-yl)hexanoic acid Chemical compound CCOC(=O)C1=COC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 FJWCNSHQAJTXOJ-CQSZACIVSA-N 0.000 description 1
• WSIHTQIVSFAGPE-QGZVFWFLSA-N (3r)-6-cyclohexyl-3-[3-(1,3-dihydroisoindole-2-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)N1CC2=CC=CC=C2C1)CCC1CCCCC1 WSIHTQIVSFAGPE-QGZVFWFLSA-N 0.000 description 1
• LLZVIOAPEOBEPJ-CQSZACIVSA-N (3r)-6-cyclohexyl-3-[3-(1h-imidazol-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(CC=2NC=CN=2)N=1)CCC1CCCCC1 LLZVIOAPEOBEPJ-CQSZACIVSA-N 0.000 description 1
• QJEYCSBKBGERMF-LJQANCHMSA-N (3r)-6-cyclohexyl-3-[3-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)N1CC2=CC=CC=C2CC1)CCC1CCCCC1 QJEYCSBKBGERMF-LJQANCHMSA-N 0.000 description 1
• YEYGDXKOJQROMI-CQSZACIVSA-N (3r)-6-cyclohexyl-3-[3-(3-methoxycarbonylazetidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C1C(C(=O)OC)CN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 YEYGDXKOJQROMI-CQSZACIVSA-N 0.000 description 1
• DROITMWAKYGARP-GFCCVEGCSA-N (3r)-6-cyclohexyl-3-[3-(methylcarbamoyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 DROITMWAKYGARP-GFCCVEGCSA-N 0.000 description 1
• MWPYNFDKMJVDMG-OAHLLOKOSA-N (3r)-6-cyclohexyl-3-[3-(morpholine-4-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)N1CCOCC1)CCC1CCCCC1 MWPYNFDKMJVDMG-OAHLLOKOSA-N 0.000 description 1
• DFDCXLNYPSCUKV-MRXNPFEDSA-N (3r)-6-cyclohexyl-3-[3-(piperidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(N=1)C(=O)N1CCCCC1)CCC1CCCCC1 DFDCXLNYPSCUKV-MRXNPFEDSA-N 0.000 description 1
• TZWWRNVPLWASAN-OAHLLOKOSA-N (3r)-6-cyclohexyl-3-[3-(propylsulfonylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CCCS(=O)(=O)CC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 TZWWRNVPLWASAN-OAHLLOKOSA-N 0.000 description 1
• PTXFEJZUTWTIOE-QGZVFWFLSA-N (3r)-6-cyclohexyl-3-[3-(pyridin-3-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(CC=2C=NC=CC=2)N=1)CCC1CCCCC1 PTXFEJZUTWTIOE-QGZVFWFLSA-N 0.000 description 1
• ONURMEDYMRDXSS-QGZVFWFLSA-N (3r)-6-cyclohexyl-3-[3-(pyridin-4-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound C([C@H](CC(=O)O)C=1ON=C(CC=2C=CN=CC=2)N=1)CCC1CCCCC1 ONURMEDYMRDXSS-QGZVFWFLSA-N 0.000 description 1
• SDPPORRAFROKQA-OAHLLOKOSA-N (3r)-6-cyclohexyl-3-[3-[(2-ethoxy-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CCOC(=O)COCC1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 SDPPORRAFROKQA-OAHLLOKOSA-N 0.000 description 1
• ORQAUPCSRLPYCY-MRXNPFEDSA-N (3r)-6-cyclohexyl-3-[3-[2-(dimethylamino)ethyl-methylcarbamoyl]-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound CN(C)CCN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 ORQAUPCSRLPYCY-MRXNPFEDSA-N 0.000 description 1
• FXSYCSRDFCTIAO-OAHLLOKOSA-N (3r)-6-cyclohexyl-3-[3-[3-(dimethylamino)azetidine-1-carbonyl]-1,2,4-oxadiazol-5-yl]-n-hydroxyhexanamide Chemical compound C1C(N(C)C)CN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 FXSYCSRDFCTIAO-OAHLLOKOSA-N 0.000 description 1
• SQEXOSCAVMBQFF-QGZVFWFLSA-N (3r)-6-cyclohexyl-3-[3-[4-(dimethylamino)piperidine-1-carbonyl]-1,2,4-oxadiazol-5-yl]-n-hydroxyhexanamide Chemical compound C1CC(N(C)C)CCN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 SQEXOSCAVMBQFF-QGZVFWFLSA-N 0.000 description 1
• FRBGBIMRJNZFGP-QGZVFWFLSA-N (3r)-6-cyclohexyl-3-[3-[methyl(pyridin-2-ylmethyl)carbamoyl]-1,2,4-oxadiazol-5-yl]hexanoic acid Chemical compound N=1OC([C@H](CCCC2CCCCC2)CC(O)=O)=NC=1C(=O)N(C)CC1=CC=CC=N1 FRBGBIMRJNZFGP-QGZVFWFLSA-N 0.000 description 1
• RDSYZTLSSFFDRB-CYBMUJFWSA-N (3r)-6-cyclohexyl-n-hydroxy-3-(3-methyl-1,2,4-oxadiazol-5-yl)hexanamide Chemical compound CC1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 RDSYZTLSSFFDRB-CYBMUJFWSA-N 0.000 description 1
• YHRWCPLSRDPORX-CQSZACIVSA-N (3r)-6-cyclohexyl-n-hydroxy-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)hexanamide Chemical compound CC(C)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 YHRWCPLSRDPORX-CQSZACIVSA-N 0.000 description 1
• DCQFAADCOWBVEB-CQSZACIVSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(1h-imidazol-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(CC=2NC=CN=2)N=1)CCC1CCCCC1 DCQFAADCOWBVEB-CQSZACIVSA-N 0.000 description 1
• CZVWFUCMCMGYMX-CQSZACIVSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound COCCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 CZVWFUCMCMGYMX-CQSZACIVSA-N 0.000 description 1
• GTKVSZVCSOLLRE-QGZVFWFLSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(3-morpholin-4-ylazetidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(N=1)C(=O)N1CC(C1)N1CCOCC1)CCC1CCCCC1 GTKVSZVCSOLLRE-QGZVFWFLSA-N 0.000 description 1
• ILJXZQLFIZVNAG-OAQYLSRUSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(4-pyridin-4-ylpiperidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(N=1)C(=O)N1CCC(CC1)C=1C=CN=CC=1)CCC1CCCCC1 ILJXZQLFIZVNAG-OAQYLSRUSA-N 0.000 description 1
• SJLBLWNJNDHLJT-CYBMUJFWSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound COCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 SJLBLWNJNDHLJT-CYBMUJFWSA-N 0.000 description 1
• NDQPZMLJQTZTNL-OAHLLOKOSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(propylsulfonylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound CCCS(=O)(=O)CC1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 NDQPZMLJQTZTNL-OAHLLOKOSA-N 0.000 description 1
• SQXNPCFBGUVNOP-MRXNPFEDSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(pyridin-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(CC=2N=CC=CC=2)N=1)CCC1CCCCC1 SQXNPCFBGUVNOP-MRXNPFEDSA-N 0.000 description 1
• RVWAKNLWMSGWFK-QGZVFWFLSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(pyridin-3-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(CC=2C=NC=CC=2)N=1)CCC1CCCCC1 RVWAKNLWMSGWFK-QGZVFWFLSA-N 0.000 description 1
• UCORESKGJKPJKI-QGZVFWFLSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(pyridin-4-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(CC=2C=CN=CC=2)N=1)CCC1CCCCC1 UCORESKGJKPJKI-QGZVFWFLSA-N 0.000 description 1
• BVHVBQPFFANDCW-OAHLLOKOSA-N (3r)-6-cyclohexyl-n-hydroxy-3-[3-(pyrrolidine-1-carbonyl)-1,2,4-oxadiazol-5-yl]hexanamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(N=1)C(=O)N1CCCC1)CCC1CCCCC1 BVHVBQPFFANDCW-OAHLLOKOSA-N 0.000 description 1
• OJOFMLDBXPDXLQ-VIFPVBQESA-N (4s)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-VIFPVBQESA-N 0.000 description 1
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
• VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-N 0.000 description 1
• LKYNGTHMKCTTQC-UHFFFAOYSA-N 1,2-oxazole-3-carboxamide Chemical compound NC(=O)C=1C=CON=1 LKYNGTHMKCTTQC-UHFFFAOYSA-N 0.000 description 1
• JBCFJMYPJJWIRG-UHFFFAOYSA-N 1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC=N1 JBCFJMYPJJWIRG-UHFFFAOYSA-N 0.000 description 1
• ZBCDBDFHHQCSJQ-UHFFFAOYSA-N 1-(2,6-dimethylmorpholin-4-yl)-3-[4-[3-(2,6-dimethylmorpholin-4-yl)-2-hydroxypropoxy]phenoxy]propan-2-ol Chemical compound C1C(C)OC(C)CN1CC(O)COC(C=C1)=CC=C1OCC(O)CN1CC(C)OC(C)C1 ZBCDBDFHHQCSJQ-UHFFFAOYSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• WFJXMUVBEMQYPI-CYBMUJFWSA-N 1-[5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carbonyl]azetidine-3-carboxylic acid Chemical compound C([C@H](CC(=O)NO)C=1ON=C(N=1)C(=O)N1CC(C1)C(O)=O)CCC1CCCCC1 WFJXMUVBEMQYPI-CYBMUJFWSA-N 0.000 description 1
• LMJJHTUVHUINLH-MRXNPFEDSA-N 1-[5-[(3r)-6-cyclohexyl-1-[(2-methylpropan-2-yl)oxy]-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carbonyl]azetidine-3-carboxylic acid Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CC(C1)C(O)=O)CCC1CCCCC1 LMJJHTUVHUINLH-MRXNPFEDSA-N 0.000 description 1
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• NOVIRODZMIZUPA-UHFFFAOYSA-N 2,3-dihydro-1h-isoindole;hydrochloride Chemical compound Cl.C1=CC=C2CNCC2=C1 NOVIRODZMIZUPA-UHFFFAOYSA-N 0.000 description 1
• VEFDYICPJUXKSJ-UHFFFAOYSA-N 2-(4-chlorophenoxy)-n'-hydroxyethanimidamide Chemical compound ON=C(N)COC1=CC=C(Cl)C=C1 VEFDYICPJUXKSJ-UHFFFAOYSA-N 0.000 description 1
• JDJJCAFDNKSAPX-UHFFFAOYSA-N 2-(benzenesulfonyl)-n'-hydroxyethanimidamide Chemical compound ON=C(N)CS(=O)(=O)C1=CC=CC=C1 JDJJCAFDNKSAPX-UHFFFAOYSA-N 0.000 description 1
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
• DZWAGXCZXNNAMJ-GFCCVEGCSA-N 2-[(3r)-6-cyclobutyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n,n-dimethyl-1,3-oxazole-4-carboxamide Chemical compound CN(C)C(=O)C1=COC([C@H](CCCC2CCC2)CC(=O)NO)=N1 DZWAGXCZXNNAMJ-GFCCVEGCSA-N 0.000 description 1
• LZWSPBRKBXLFSK-CYBMUJFWSA-N 2-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-5-methyl-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=C(C)OC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 LZWSPBRKBXLFSK-CYBMUJFWSA-N 0.000 description 1
• XCNVYYDGOWJOOG-CQSZACIVSA-N 2-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n,n-dimethyl-1,3-oxazole-4-carboxamide Chemical compound CN(C)C(=O)C1=COC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 XCNVYYDGOWJOOG-CQSZACIVSA-N 0.000 description 1
• RCZRGEGLYJZHEI-HXUWFJFHSA-N 2-[(3r)-6-cyclohexyl-1-oxo-1-(phenylmethoxyamino)hexan-3-yl]-5-methyl-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=C(C)OC([C@H](CCCC2CCCCC2)CC(=O)NOCC=2C=CC=CC=2)=N1 RCZRGEGLYJZHEI-HXUWFJFHSA-N 0.000 description 1
• VHAZFRSITBUFOH-OAQYLSRUSA-N 2-[(3r)-6-cyclohexyl-1-oxo-1-(phenylmethoxyamino)hexan-3-yl]-n,n-dimethyl-1,3-oxazole-4-carboxamide Chemical compound CN(C)C(=O)C1=COC([C@H](CCCC2CCCCC2)CC(=O)NOCC=2C=CC=CC=2)=N1 VHAZFRSITBUFOH-OAQYLSRUSA-N 0.000 description 1
• GSHCXJWZWQAWFQ-CQSZACIVSA-N 2-[[2-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-5-methyl-1,3-oxazole-4-carbonyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=C(C)OC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 GSHCXJWZWQAWFQ-CQSZACIVSA-N 0.000 description 1
• LMPFHGRKXZOLQD-CYBMUJFWSA-N 2-[[5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]methoxy]acetic acid Chemical compound C([C@H](CC(=O)NO)C=1ON=C(COCC(O)=O)N=1)CCC1CCCCC1 LMPFHGRKXZOLQD-CYBMUJFWSA-N 0.000 description 1
• LGSPQFFBRRZRCY-TYZXPVIJSA-N 2-[[5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]methoxy]propanoic acid Chemical compound OC(=O)C(C)OCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 LGSPQFFBRRZRCY-TYZXPVIJSA-N 0.000 description 1
• VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
• JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
• PBVZQAXFSQKDKK-UHFFFAOYSA-N 3-Methoxy-3-oxopropanoic acid Chemical compound COC(=O)CC(O)=O PBVZQAXFSQKDKK-UHFFFAOYSA-N 0.000 description 1
• GFNVEWVWSNVREJ-CYBMUJFWSA-N 3-[5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]propanoic acid Chemical compound C([C@H](CC(=O)NO)C=1ON=C(CCC(O)=O)N=1)CCC1CCCCC1 GFNVEWVWSNVREJ-CYBMUJFWSA-N 0.000 description 1
• OCOBFMZGRJOSOU-UHFFFAOYSA-N 3-o-tert-butyl 1-o-ethyl propanedioate Chemical compound CCOC(=O)CC(=O)OC(C)(C)C OCOBFMZGRJOSOU-UHFFFAOYSA-N 0.000 description 1
• YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical compound O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 description 1
• AEGZLYNAJWQQTO-UHFFFAOYSA-N 4-(azetidin-3-yl)morpholine;hydrochloride Chemical compound Cl.C1NCC1N1CCOCC1 AEGZLYNAJWQQTO-UHFFFAOYSA-N 0.000 description 1
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-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
• BLLBEWAILBDISW-CQSZACIVSA-N 4-o-tert-butyl 1-o-[(e)-(1,2-diamino-2-oxoethylidene)amino] (2r)-2-(3-cyclohexylpropyl)butanedioate Chemical compound NC(=O)C(/N)=N/OC(=O)[C@@H](CC(=O)OC(C)(C)C)CCCC1CCCCC1 BLLBEWAILBDISW-CQSZACIVSA-N 0.000 description 1
• WGEWXQCHLFFUGM-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1,6-naphthyridine;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2CNCCC2=N1 WGEWXQCHLFFUGM-UHFFFAOYSA-N 0.000 description 1
• SJQRQOKXQKVJGJ-UHFFFAOYSA-N 5-(2-aminoethylamino)naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(NCCN)=CC=CC2=C1S(O)(=O)=O SJQRQOKXQKVJGJ-UHFFFAOYSA-N 0.000 description 1
• XLQHLJMLDXJGEA-RFVHGSKJSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carboxamide;hydrate Chemical compound O.NC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 XLQHLJMLDXJGEA-RFVHGSKJSA-N 0.000 description 1
• SJSLPFGXTJRLHN-OAHLLOKOSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-(cyclopropylmethyl)-1,2,4-oxadiazole-3-carboxamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(N=1)C(=O)NCC1CC1)CCC1CCCCC1 SJSLPFGXTJRLHN-OAHLLOKOSA-N 0.000 description 1
• QYMZESBXBCDLLC-MRXNPFEDSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-(pyridin-2-ylmethyl)-1,2,4-oxadiazole-3-carboxamide Chemical compound C([C@H](CC(=O)NO)C=1ON=C(N=1)C(=O)NCC=1N=CC=CC=1)CCC1CCCCC1 QYMZESBXBCDLLC-MRXNPFEDSA-N 0.000 description 1
• KZWFDOMNRZTNNP-QGZVFWFLSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-[(2-methoxyphenyl)methyl]-1,2,4-oxadiazole-3-carboxamide Chemical compound COC1=CC=CC=C1CNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 KZWFDOMNRZTNNP-QGZVFWFLSA-N 0.000 description 1
• LCKRXCRJZLKHCE-MRXNPFEDSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-[2-(dimethylamino)ethyl]-n-methyl-1,2,4-oxadiazole-3-carboxamide Chemical compound CN(C)CCN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 LCKRXCRJZLKHCE-MRXNPFEDSA-N 0.000 description 1
• BWWHNHOPLVHGAZ-QGZVFWFLSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-[3-(dimethylamino)propyl]-n-methyl-1,2,4-oxadiazole-3-carboxamide Chemical compound CN(C)CCCN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 BWWHNHOPLVHGAZ-QGZVFWFLSA-N 0.000 description 1
• OFLBRKJKSKQKCC-QGZVFWFLSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-methyl-n-(pyridin-2-ylmethyl)-1,2,4-oxadiazole-3-carboxamide Chemical compound N=1OC([C@H](CCCC2CCCCC2)CC(=O)NO)=NC=1C(=O)N(C)CC1=CC=CC=N1 OFLBRKJKSKQKCC-QGZVFWFLSA-N 0.000 description 1
• IALSBWBRIDYNGC-CQSZACIVSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-propyl-1,2,4-oxadiazole-3-carboxamide Chemical compound CCCNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 IALSBWBRIDYNGC-CQSZACIVSA-N 0.000 description 1
• KGAZHHPYIJCKFU-UHFFFAOYSA-N 5-cyclohexylpentanoyl chloride Chemical compound ClC(=O)CCCCC1CCCCC1 KGAZHHPYIJCKFU-UHFFFAOYSA-N 0.000 description 1
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
• 108010023728 Alloderm Proteins 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 108010001781 Apligraf Proteins 0.000 description 1
• 101100481033 Arabidopsis thaliana TGA7 gene Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010054793 Arterial fibrosis Diseases 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 101800001415 Bri23 peptide Proteins 0.000 description 1
• 101800000655 C-terminal peptide Proteins 0.000 description 1
• 102400000107 C-terminal peptide Human genes 0.000 description 1
• 102100031168 CCN family member 2 Human genes 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 101800005309 Carboxy-terminal peptide Proteins 0.000 description 1
• 208000002177 Cataract Diseases 0.000 description 1
• OLVPQBGMUGIKIW-UHFFFAOYSA-N Chymostatin Natural products C=1C=CC=CC=1CC(C=O)NC(=O)C(C(C)CC)NC(=O)C(C1NC(N)=NCC1)NC(=O)NC(C(O)=O)CC1=CC=CC=C1 OLVPQBGMUGIKIW-UHFFFAOYSA-N 0.000 description 1
• 208000032544 Cicatrix Diseases 0.000 description 1
• 206010009208 Cirrhosis alcoholic Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 102100036213 Collagen alpha-2(I) chain Human genes 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 0.000 description 1
• 108050005238 Collagenase 3 Proteins 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• 208000001708 Dupuytren contracture Diseases 0.000 description 1
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
• 102100028412 Fibroblast growth factor 10 Human genes 0.000 description 1
• 108090001047 Fibroblast growth factor 10 Proteins 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 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 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 description 1
• 101000875067 Homo sapiens Collagen alpha-2(I) chain Proteins 0.000 description 1
• 101001011906 Homo sapiens Matrix metalloproteinase-14 Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 101150088952 IGF1 gene Proteins 0.000 description 1
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
• 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
• 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
• 208000029523 Interstitial Lung disease Diseases 0.000 description 1
• 206010058031 Joint adhesion Diseases 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 101150014058 MMP1 gene Proteins 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 102100030417 Matrilysin Human genes 0.000 description 1
• 108090000855 Matrilysin Proteins 0.000 description 1
• 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 1
• 102100030201 Matrix metalloproteinase-15 Human genes 0.000 description 1
• 108090000560 Matrix metalloproteinase-15 Proteins 0.000 description 1
• 102100030200 Matrix metalloproteinase-16 Human genes 0.000 description 1
• 108090000561 Matrix metalloproteinase-16 Proteins 0.000 description 1
• 102100030219 Matrix metalloproteinase-17 Human genes 0.000 description 1
• 108090000585 Matrix metalloproteinase-17 Proteins 0.000 description 1
• 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 1
• 108010042991 NFF 2 Proteins 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 102100030411 Neutrophil collagenase Human genes 0.000 description 1
• 101710118230 Neutrophil collagenase Proteins 0.000 description 1
• 102000056189 Neutrophil collagenases Human genes 0.000 description 1
• 108030001564 Neutrophil collagenases Proteins 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 206010034238 Pelvic adhesions Diseases 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 108010003894 Protein-Lysine 6-Oxidase Proteins 0.000 description 1
• 102100026858 Protein-lysine 6-oxidase Human genes 0.000 description 1
• 102000003743 Relaxin Human genes 0.000 description 1
• 108090000103 Relaxin Proteins 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 108010041312 SNK 863 Proteins 0.000 description 1
• 206010039580 Scar Diseases 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 238000006600 Stobbe condensation reaction Methods 0.000 description 1
• 101710108790 Stromelysin-1 Proteins 0.000 description 1
• 239000012505 Superdex™ Substances 0.000 description 1
• 208000002847 Surgical Wound Diseases 0.000 description 1
• 102400000398 Transforming growth factor beta-3 Human genes 0.000 description 1
• 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 101710162629 Trypsin inhibitor Proteins 0.000 description 1
• 229940122618 Trypsin inhibitor Drugs 0.000 description 1
• 102100031358 Urokinase-type plasminogen activator Human genes 0.000 description 1
• AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 208000010002 alcoholic liver cirrhosis Diseases 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 150000008052 alkyl sulfonates Chemical group 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
• 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
• 235000011130 ammonium sulphate Nutrition 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 230000002942 anti-growth Effects 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 238000010936 aqueous wash Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000005228 aryl sulfonate group Chemical group 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 150000001511 astacins Chemical class 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
• GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 210000002469 basement membrane Anatomy 0.000 description 1
• 229950001858 batimastat Drugs 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 239000001273 butane Substances 0.000 description 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 238000007707 calorimetry Methods 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 230000009787 cardiac fibrosis Effects 0.000 description 1
• 108020001778 catalytic domains Proteins 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000004709 cell invasion Effects 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 108010086192 chymostatin Proteins 0.000 description 1
• 229940096422 collagen type i Drugs 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 108700004333 collagenase 1 Proteins 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 238000002316 cosmetic surgery Methods 0.000 description 1
• KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
• XBCLZRKPHNXURA-PFEQFJNWSA-N cyclohexanamine;(2r)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-phenylpentanoic acid Chemical compound NC1CCCCC1.CC(C)(C)OC(=O)C[C@H](C(O)=O)CCCC1=CC=CC=C1 XBCLZRKPHNXURA-PFEQFJNWSA-N 0.000 description 1
• KRIHOLBDXJJJFL-PFEQFJNWSA-N cyclohexanamine;(2r)-5-cyclohexyl-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pentanoic acid Chemical compound NC1CCCCC1.CC(C)(C)OC(=O)C[C@H](C(O)=O)CCCC1CCCCC1 KRIHOLBDXJJJFL-PFEQFJNWSA-N 0.000 description 1
• IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• CZWCKYRVOZZJNM-USOAJAOKSA-N dehydroepiandrosterone sulfate Chemical compound C1[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 CZWCKYRVOZZJNM-USOAJAOKSA-N 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 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 1
• 208000033679 diabetic kidney disease Diseases 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 108010037444 diisopropylglutathione ester Proteins 0.000 description 1
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 238000010410 dusting Methods 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• QGYKRMZPOOILBA-UHFFFAOYSA-N ethyl (2e)-2-amino-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(\N)=N\O QGYKRMZPOOILBA-UHFFFAOYSA-N 0.000 description 1
• JZJQCLZQSHLSFB-WCCKRBBISA-N ethyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)CO JZJQCLZQSHLSFB-WCCKRBBISA-N 0.000 description 1
• GTOOKUANDJVESR-OAHLLOKOSA-N ethyl 3-[5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]propanoate Chemical compound CCOC(=O)CCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 GTOOKUANDJVESR-OAHLLOKOSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• PZRVWUBJSGCQME-UHFFFAOYSA-N ethyl acetate pentane Chemical compound CCCCC.CCCCC.CCOC(C)=O PZRVWUBJSGCQME-UHFFFAOYSA-N 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 239000000416 hydrocolloid Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical class OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
• 235000015110 jellies Nutrition 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• OZSJLLVVZFTDEY-HJXLNUONSA-N methyl (2s,3r)-2-amino-3-hydroxybutanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)[C@@H](C)O OZSJLLVVZFTDEY-HJXLNUONSA-N 0.000 description 1
• ZNCOYFLGZOWPTN-CQSZACIVSA-N methyl 1-[5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carbonyl]azetidine-3-carboxylate Chemical compound C1C(C(=O)OC)CN1C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 ZNCOYFLGZOWPTN-CQSZACIVSA-N 0.000 description 1
• LSPIBFBLVJJFHB-QGZVFWFLSA-N methyl 2-[(3r)-6-cyclohexyl-1-[(2-methylpropan-2-yl)oxy]-1-oxohexan-3-yl]-5-methyl-1,3-oxazole-4-carboxylate Chemical compound O1C(C)=C(C(=O)OC)N=C1[C@@H](CC(=O)OC(C)(C)C)CCCC1CCCCC1 LSPIBFBLVJJFHB-QGZVFWFLSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 201000006938 muscular dystrophy Diseases 0.000 description 1
• UNKQCVYVFHGUTQ-UHFFFAOYSA-N n'-hydroxy-2-methoxyethanimidamide Chemical compound COCC(N)=NO UNKQCVYVFHGUTQ-UHFFFAOYSA-N 0.000 description 1
• JHRDEHLFNLLCQS-UHFFFAOYSA-N n'-hydroxy-2-methylpropanimidamide Chemical compound CC(C)C(N)=NO JHRDEHLFNLLCQS-UHFFFAOYSA-N 0.000 description 1
• MZBUMLNJVFZLRR-UHFFFAOYSA-N n'-hydroxy-2-propylsulfonylethanimidamide Chemical compound CCCS(=O)(=O)C\C(N)=N\O MZBUMLNJVFZLRR-UHFFFAOYSA-N 0.000 description 1
• PXMSSPLOGAKGEO-UHFFFAOYSA-N n'-hydroxy-2-pyridin-2-ylethanimidamide Chemical compound ON=C(N)CC1=CC=CC=N1 PXMSSPLOGAKGEO-UHFFFAOYSA-N 0.000 description 1
• ORONPIWHCJVHPQ-UHFFFAOYSA-N n'-hydroxy-3-methoxypropanimidamide Chemical compound COCCC(N)=NO ORONPIWHCJVHPQ-UHFFFAOYSA-N 0.000 description 1
• ISUFAXRPGSQHIC-UHFFFAOYSA-N n'-hydroxy-3-oxo-3-pyrrolidin-1-ylpropanimidamide Chemical compound ON=C(N)CC(=O)N1CCCC1 ISUFAXRPGSQHIC-UHFFFAOYSA-N 0.000 description 1
• HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
• SORARJZLMNRBAQ-UHFFFAOYSA-N n,n',n'-trimethylpropane-1,3-diamine Chemical compound CNCCCN(C)C SORARJZLMNRBAQ-UHFFFAOYSA-N 0.000 description 1
• IRQWCOFOSMREBQ-UHFFFAOYSA-N n,n-dimethylazetidin-3-amine Chemical compound CN(C)C1CNC1 IRQWCOFOSMREBQ-UHFFFAOYSA-N 0.000 description 1
• YFJAIURZMRJPDB-UHFFFAOYSA-N n,n-dimethylpiperidin-4-amine Chemical compound CN(C)C1CCNCC1 YFJAIURZMRJPDB-UHFFFAOYSA-N 0.000 description 1
• IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
• RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
• RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 102000045246 noggin Human genes 0.000 description 1
• 108700007229 noggin Proteins 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
• HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 108010000416 ovomacroglobulin Proteins 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
• 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 235000019809 paraffin wax Nutrition 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 102000040430 polynucleotide Human genes 0.000 description 1
• 108091033319 polynucleotide Proteins 0.000 description 1
• 239000002157 polynucleotide Substances 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229950008882 polysorbate Drugs 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000010289 potassium nitrite Nutrition 0.000 description 1
• 239000004304 potassium nitrite Substances 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 244000144977 poultry Species 0.000 description 1
• 235000013594 poultry meat Nutrition 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 210000004879 pulmonary tissue Anatomy 0.000 description 1
• SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000002207 retinal effect Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 230000036573 scar formation Effects 0.000 description 1
• 238000007790 scraping Methods 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000015607 signal release Effects 0.000 description 1
• 210000003625 skull Anatomy 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 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
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 230000003393 splenic effect Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 238000004441 surface measurement Methods 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• TWUDGPSVFIBDLQ-CQSZACIVSA-N tert-butyl (3r)-3-(3-carbamoyl-1,2,4-oxadiazol-5-yl)-6-cyclohexylhexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(N)=O)CCC1CCCCC1 TWUDGPSVFIBDLQ-CQSZACIVSA-N 0.000 description 1
• CNAITZLJHAGECR-MRXNPFEDSA-N tert-butyl (3r)-6-cyclohexyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)hexanoate Chemical compound CC1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 CNAITZLJHAGECR-MRXNPFEDSA-N 0.000 description 1
• YWMUBMIHINEZQW-DUSLRRAJSA-N tert-butyl (3r)-6-cyclohexyl-3-[(1-methoxy-1,3-dioxobutan-2-yl)carbamoyl]hexanoate Chemical compound COC(=O)C(C(C)=O)NC(=O)[C@@H](CC(=O)OC(C)(C)C)CCCC1CCCCC1 YWMUBMIHINEZQW-DUSLRRAJSA-N 0.000 description 1
• LFMJALRQHQJFMO-QGZVFWFLSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound COCCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 LFMJALRQHQJFMO-QGZVFWFLSA-N 0.000 description 1
• UCPDZGBPNPZITE-JOCHJYFZSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C=1ON=C(N=1)C(=O)N1CC2=CC=CC=C2CC1)CCC1CCCCC1 UCPDZGBPNPZITE-JOCHJYFZSA-N 0.000 description 1
• PZVFAFUVDPWPHB-GOSISDBHSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-(propylsulfonylmethyl)-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound CCCS(=O)(=O)CC1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 PZVFAFUVDPWPHB-GOSISDBHSA-N 0.000 description 1
• UMPDLFNQFQCKMI-WHCXFUJUSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[(1-ethoxy-1-oxopropan-2-yl)oxymethyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound CCOC(=O)C(C)OCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 UMPDLFNQFQCKMI-WHCXFUJUSA-N 0.000 description 1
• GDCDMIWAQRJMFA-OAQYLSRUSA-N tert-butyl (3r)-6-cyclohexyl-3-[3-[(4-methylphenyl)sulfonyloxymethyl]-1,2,4-oxadiazol-5-yl]hexanoate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 GDCDMIWAQRJMFA-OAQYLSRUSA-N 0.000 description 1
• OSWULUXZFOQIRU-UHFFFAOYSA-N tert-butyl 2-aminoacetate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)CN OSWULUXZFOQIRU-UHFFFAOYSA-N 0.000 description 1
• TXFDXZXEQNCRTM-UHFFFAOYSA-N tert-butyl 3-iodocyclobutane-1-carboxylate Chemical compound CC(C)(C)OC(=O)C1CC(I)C1 TXFDXZXEQNCRTM-UHFFFAOYSA-N 0.000 description 1
• 238000010998 test method Methods 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
• 238000002411 thermogravimetry Methods 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
• 229940099259 vaseline Drugs 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 150000003738 xylenes Chemical class 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1
• NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
• 229960001763 zinc sulfate Drugs 0.000 description 1
• 229910000368 zinc sulfate Inorganic materials 0.000 description 1