CA2051782A1

CA2051782A1 - Aminoesters de rapamycine

Aminoesters de rapamycine

Info

Publication number: CA2051782A1
Authority: CA; Canada
Prior art keywords: carbon atoms; rapamycin; compound; acceptable salt; carbonyl
Prior art date: 1990-09-28
Legal status : Abandoned

Application number

CA 2051782

Other languages

English (en)

Inventor

Amedeo A. Failli

Craig E. Caufield

Robert J. Steffan

Current Assignee

Wyeth LLC

Original Assignee

Individual

Priority date

1990-09-28

Filing date

1991-09-18

Publication date

1992-03-29

1991-02-19 Priority claimed from US07/657,294 external-priority patent/US5130307A/en

1991-09-18 Application filed by Individual filed Critical Individual

1992-03-29 Publication of CA2051782A1 publication Critical patent/CA2051782A1/fr

Status Abandoned legal-status Critical Current

Links

QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title description 31
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 title description 28
229960002930 sirolimus Drugs 0.000 title description 28
150000001875 compounds Chemical class 0.000 claims abstract description 71
-1 guanylalkyl Chemical group 0.000 claims abstract description 31
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
150000003839 salts Chemical class 0.000 claims abstract description 24
125000000217 alkyl group Chemical group 0.000 claims abstract description 20
239000001257 hydrogen Substances 0.000 claims abstract description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 12
150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
201000010099 disease Diseases 0.000 claims abstract description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
125000001475 halogen functional group Chemical group 0.000 claims abstract description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
208000023275 Autoimmune disease Diseases 0.000 claims abstract description 4
206010061218 Inflammation Diseases 0.000 claims abstract description 4
125000006350 alkyl thio alkyl group Chemical group 0.000 claims abstract description 4
125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 4
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230000004054 inflammatory process Effects 0.000 claims abstract description 4
125000005358 mercaptoalkyl group Chemical group 0.000 claims abstract description 4
238000002054 transplantation Methods 0.000 claims abstract description 4
150000002431 hydrogen Chemical group 0.000 claims abstract 6
125000004432 carbon atom Chemical group C* 0.000 claims description 52
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 32
239000000203 mixture Substances 0.000 claims description 18
238000000034 method Methods 0.000 claims description 14
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
239000004472 Lysine Substances 0.000 claims description 4
239000002552 dosage form Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
HWBAHOVOSOAFLE-UHFFFAOYSA-N 2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(=O)NCC(O)=O HWBAHOVOSOAFLE-UHFFFAOYSA-N 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
YRXIMPFOTQVOHG-UHFFFAOYSA-N 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OC(C)(C)C YRXIMPFOTQVOHG-UHFFFAOYSA-N 0.000 claims 2
LDRWTKQWSXGSTM-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)NC(CC(O)=O)C(=O)OCC1=CC=CC=C1 LDRWTKQWSXGSTM-UHFFFAOYSA-N 0.000 claims 2
YGSRAYJBEREVRB-UHFFFAOYSA-N 5-[(2-methylpropan-2-yl)oxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid Chemical compound CC(C)(C)OC(=O)CCC(C(O)=O)NC(=O)OC(C)(C)C YGSRAYJBEREVRB-UHFFFAOYSA-N 0.000 claims 2
SOHLZANWVLCPHK-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC(=O)OCC1=CC=CC=C1 SOHLZANWVLCPHK-UHFFFAOYSA-N 0.000 claims 1
YMOYURYWGUWMFM-UHFFFAOYSA-N 5-[(2-methylpropan-2-yl)oxy]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid Chemical compound CC(C)(C)OC(=O)NC(CCC(O)=O)C(=O)OC(C)(C)C YMOYURYWGUWMFM-UHFFFAOYSA-N 0.000 claims 1
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
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UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
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238000011735 C3H mouse Methods 0.000 description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
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PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 4
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WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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DXWBBEQQKGMAGO-INIZCTEOSA-N (2s)-2-(9h-fluoren-1-ylmethoxycarbonylamino)-3-hydroxypropanoic acid Chemical compound C1C2=CC=CC=C2C2=C1C(COC(=O)N[C@@H](CO)C(O)=O)=CC=C2 DXWBBEQQKGMAGO-INIZCTEOSA-N 0.000 description 2
LRXAWNDHHPLJOF-JTQLQIEISA-N (2s)-2-(ethoxycarbonylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound CCOC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 LRXAWNDHHPLJOF-JTQLQIEISA-N 0.000 description 2
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NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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