NO306552B1 - Analogifremgangsmåte for fremstilling av hemmere av retrovirale proteaser - Google Patents
Analogifremgangsmåte for fremstilling av hemmere av retrovirale proteaser Download PDFInfo
- Publication number
- NO306552B1 NO306552B1 NO905410A NO905410A NO306552B1 NO 306552 B1 NO306552 B1 NO 306552B1 NO 905410 A NO905410 A NO 905410A NO 905410 A NO905410 A NO 905410A NO 306552 B1 NO306552 B1 NO 306552B1
- Authority
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- Norway
- Prior art keywords
- alkyl
- amino
- hydrogen
- substituted
- het
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Links
- 238000000034 method Methods 0.000 title claims description 26
- 238000002360 preparation method Methods 0.000 title claims description 14
- 239000003112 inhibitor Substances 0.000 title description 7
- 108091005804 Peptidases Proteins 0.000 title description 6
- 239000004365 Protease Substances 0.000 title description 6
- 230000001177 retroviral effect Effects 0.000 title description 3
- 102000035195 Peptidases Human genes 0.000 title description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 35
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 23
- 150000001413 amino acids Chemical class 0.000 claims abstract description 22
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 21
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 18
- 239000002253 acid Substances 0.000 claims abstract description 17
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 17
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 11
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 8
- 125000003147 glycosyl group Chemical group 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 150000001312 aldohexoses Chemical class 0.000 claims abstract description 3
- 150000001320 aldopentoses Chemical class 0.000 claims abstract description 3
- 125000005640 glucopyranosyl group Chemical group 0.000 claims abstract description 3
- 150000002574 ketohexoses Chemical class 0.000 claims abstract description 3
- 150000002581 ketopentoses Chemical class 0.000 claims abstract description 3
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 3
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 3
- -1 aza amino acid Chemical class 0.000 claims description 272
- 239000001257 hydrogen Substances 0.000 claims description 93
- 229910052739 hydrogen Inorganic materials 0.000 claims description 93
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 70
- 150000001875 compounds Chemical class 0.000 claims description 54
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 47
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 46
- 125000004429 atom Chemical group 0.000 claims description 32
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 229920006395 saturated elastomer Polymers 0.000 claims description 23
- 235000001014 amino acid Nutrition 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000004434 sulfur atom Chemical group 0.000 claims description 14
- 125000003368 amide group Chemical group 0.000 claims description 13
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 239000012634 fragment Substances 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 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 10
- 150000003457 sulfones Chemical class 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 150000001768 cations Chemical class 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000003462 sulfoxides Chemical class 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- FVHVJARLLUJUTI-UHFFFAOYSA-N 2-cyclooctylazocane Chemical compound C1CCCCCCC1C1NCCCCCC1 FVHVJARLLUJUTI-UHFFFAOYSA-N 0.000 claims description 6
- 125000005518 carboxamido group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000005936 piperidyl group Chemical group 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 5
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 4
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 4
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 150000002243 furanoses Chemical class 0.000 claims description 4
- 125000000625 hexosyl group Chemical group 0.000 claims description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 150000007857 hydrazones Chemical class 0.000 claims description 4
- 125000006302 indol-3-yl methyl group Chemical group [H]N1C([H])=C(C2=C([H])C([H])=C([H])C([H])=C12)C([H])([H])* 0.000 claims description 4
- 125000001805 pentosyl group Chemical group 0.000 claims description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- GTQXMAIXVFLYKF-UHFFFAOYSA-N thiochrome Chemical compound CC1=NC=C2CN3C(C)=C(CCO)SC3=NC2=N1 GTQXMAIXVFLYKF-UHFFFAOYSA-N 0.000 claims description 4
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
- 150000001371 alpha-amino acids Chemical class 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 claims description 2
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 125000000704 aldohexosyl group Chemical group 0.000 claims description 2
- 125000002732 aldopentosyl group Chemical group 0.000 claims description 2
- 150000001330 aldotetroses Chemical class 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000006622 cycloheptylmethyl group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000000369 oxido group Chemical group [*]=O 0.000 claims description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 17
- 150000003215 pyranoses Chemical class 0.000 claims 3
- 125000003843 furanosyl group Chemical group 0.000 claims 2
- 125000006702 (C1-C18) alkyl group Chemical group 0.000 claims 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
- 125000004965 chloroalkyl group Chemical group 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 125000003712 glycosamine group Chemical group 0.000 claims 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 abstract 1
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 50
- 230000015572 biosynthetic process Effects 0.000 description 34
- 238000003786 synthesis reaction Methods 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 26
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 25
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 229940024606 amino acid Drugs 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
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- 239000000203 mixture Substances 0.000 description 14
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 108010010369 HIV Protease Proteins 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- TYFJTEPDESMEHE-UHFFFAOYSA-N 6,8-dihydroxy-3-[2-(4-methoxyphenyl)ethyl]-3,4-dihydroisochromen-1-one Chemical compound C1=CC(OC)=CC=C1CCC1OC(=O)C2=C(O)C=C(O)C=C2C1 TYFJTEPDESMEHE-UHFFFAOYSA-N 0.000 description 7
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 7
- SMVMLJLMMUGRPU-UHFFFAOYSA-N bis(aminomethyl)phosphinic acid;hydrochloride Chemical compound Cl.NCP(O)(=O)CN SMVMLJLMMUGRPU-UHFFFAOYSA-N 0.000 description 7
- 208000030507 AIDS Diseases 0.000 description 6
- 102100034349 Integrase Human genes 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
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- 108090000790 Enzymes Proteins 0.000 description 5
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 4
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- 238000004458 analytical method Methods 0.000 description 4
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- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
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- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 4
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- 229920002113 octoxynol Polymers 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- XNQULTQRGBXLIA-UHFFFAOYSA-O phosphonic anhydride Chemical compound O[P+](O)=O XNQULTQRGBXLIA-UHFFFAOYSA-O 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 108010089520 pol Gene Products Proteins 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003148 prolines Chemical class 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- PAQZWJGSJMLPMG-UHFFFAOYSA-N propylphosphonic anhydride Substances CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- VNUORQWNUXXHLX-UHFFFAOYSA-N pyrazolidine-3-carboxylic acid Chemical compound OC(=O)C1CCNN1 VNUORQWNUXXHLX-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 241000894007 species Species 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
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N tryptophan Chemical compound C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3941607 | 1989-12-16 | ||
| DE4018942 | 1990-06-13 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO905410D0 NO905410D0 (no) | 1990-12-14 |
| NO905410L NO905410L (no) | 1991-06-17 |
| NO306552B1 true NO306552B1 (no) | 1999-11-22 |
Family
ID=25888063
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO905410A NO306552B1 (no) | 1989-12-16 | 1990-12-14 | Analogifremgangsmåte for fremstilling av hemmere av retrovirale proteaser |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5629431A (xx) |
| EP (1) | EP0435059B1 (xx) |
| JP (1) | JP2816253B2 (xx) |
| KR (1) | KR100203231B1 (xx) |
| AT (1) | ATE159946T1 (xx) |
| AU (1) | AU641197B2 (xx) |
| CA (1) | CA2032303C (xx) |
| DE (2) | DE59010771D1 (xx) |
| DK (1) | DK0435059T3 (xx) |
| ES (1) | ES2110404T3 (xx) |
| FI (1) | FI906140A (xx) |
| GR (1) | GR3025765T3 (xx) |
| HU (1) | HUT59147A (xx) |
| IE (1) | IE904516A1 (xx) |
| IL (1) | IL96677A0 (xx) |
| NO (1) | NO306552B1 (xx) |
| NZ (1) | NZ236461A (xx) |
| PL (1) | PL288270A1 (xx) |
| PT (1) | PT96180B (xx) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05508846A (ja) * | 1990-07-06 | 1993-12-09 | スミスクライン・ビーチャム・コーポレイション | アスパラギン酸プロテアーゼ抑制剤 |
| US5563121A (en) * | 1992-01-09 | 1996-10-08 | The Scripps Research Institute | Peptide linkage unit |
| DE4220566A1 (de) * | 1992-06-24 | 1994-01-20 | Hoechst Ag | Inhibitoren retroviraler Proteasen |
| US5559256A (en) * | 1992-07-20 | 1996-09-24 | E. R. Squibb & Sons, Inc. | Aminediol protease inhibitors |
| DE4310815A1 (de) * | 1993-04-02 | 1994-10-06 | Hoechst Ag | Neue Bis(aminomethyl)phosphinsäure-Derviate und Verfahren zur Herstellung von Bis(aminomethyl)phosphinsäure-Derivaten |
| JP4482883B2 (ja) | 2003-05-22 | 2010-06-16 | リードケミカル株式会社 | 抗ウイルス作用を有する化合物およびその配合剤 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3359266A (en) * | 1966-06-10 | 1967-12-19 | Monsanto Co | Process for preparing phosphorus-containing mannich bases |
| US4100275A (en) * | 1975-01-27 | 1978-07-11 | Hoffmann-La Roche Inc. | Compositions having antibiotic properties |
| NZ218937A (en) * | 1986-01-16 | 1990-03-27 | Abbott Lab | Functionalised peptidyl aminodiols and -triols as renin inhibitors and pharmaceutical compositions |
| EP0309766B1 (en) * | 1987-09-29 | 1998-04-15 | Banyu Pharmaceutical Co., Ltd. | N-acylamino acid derivatives and their use |
| DE3824961A1 (de) * | 1988-07-22 | 1990-01-25 | Basf Ag | Verfahren zur herstellung von bis(aminomethyl)-phosphinsaeure oder deren sauren oder basischen salzen |
| EP0409962B1 (de) * | 1989-02-10 | 1995-12-06 | SCHRAMM, Wolfgang | Mittel zur hemmung von hiv-proteasen |
-
1990
- 1990-12-11 DK DK90123779T patent/DK0435059T3/da active
- 1990-12-11 EP EP90123779A patent/EP0435059B1/de not_active Expired - Lifetime
- 1990-12-11 AT AT90123779T patent/ATE159946T1/de not_active IP Right Cessation
- 1990-12-11 DE DE59010771T patent/DE59010771D1/de not_active Expired - Lifetime
- 1990-12-11 ES ES90123779T patent/ES2110404T3/es not_active Expired - Lifetime
- 1990-12-11 DE DE4039569A patent/DE4039569A1/de not_active Withdrawn
- 1990-12-13 FI FI906140A patent/FI906140A/fi not_active Application Discontinuation
- 1990-12-13 PT PT96180A patent/PT96180B/pt not_active IP Right Cessation
- 1990-12-14 CA CA002032303A patent/CA2032303C/en not_active Expired - Lifetime
- 1990-12-14 HU HU908276A patent/HUT59147A/hu unknown
- 1990-12-14 IE IE451690A patent/IE904516A1/en not_active Application Discontinuation
- 1990-12-14 IL IL96677A patent/IL96677A0/xx unknown
- 1990-12-14 JP JP2419203A patent/JP2816253B2/ja not_active Expired - Lifetime
- 1990-12-14 NZ NZ236461A patent/NZ236461A/xx unknown
- 1990-12-14 NO NO905410A patent/NO306552B1/no not_active IP Right Cessation
- 1990-12-14 AU AU68025/90A patent/AU641197B2/en not_active Ceased
- 1990-12-14 PL PL28827090A patent/PL288270A1/xx unknown
- 1990-12-15 KR KR1019900020696A patent/KR100203231B1/ko not_active IP Right Cessation
-
1995
- 1995-06-07 US US08/479,562 patent/US5629431A/en not_active Expired - Lifetime
-
1997
- 1997-12-23 GR GR970403416T patent/GR3025765T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US5629431A (en) | 1997-05-13 |
| AU641197B2 (en) | 1993-09-16 |
| PT96180B (pt) | 1998-05-29 |
| DK0435059T3 (da) | 1998-07-27 |
| IE904516A1 (en) | 1991-06-19 |
| NO905410L (no) | 1991-06-17 |
| DE59010771D1 (de) | 1997-12-11 |
| EP0435059B1 (de) | 1997-11-05 |
| JPH05331067A (ja) | 1993-12-14 |
| AU6802590A (en) | 1991-06-20 |
| KR100203231B1 (ko) | 1999-06-15 |
| NO905410D0 (no) | 1990-12-14 |
| JP2816253B2 (ja) | 1998-10-27 |
| ATE159946T1 (de) | 1997-11-15 |
| NZ236461A (en) | 1993-08-26 |
| GR3025765T3 (en) | 1998-03-31 |
| PL288270A1 (en) | 1992-08-24 |
| EP0435059A1 (de) | 1991-07-03 |
| HUT59147A (en) | 1992-04-28 |
| FI906140A (fi) | 1991-06-17 |
| ES2110404T3 (es) | 1998-02-16 |
| KR910011889A (ko) | 1991-08-07 |
| IL96677A0 (en) | 1991-09-16 |
| CA2032303A1 (en) | 1991-06-17 |
| HU908276D0 (en) | 1991-06-28 |
| DE4039569A1 (de) | 1991-06-20 |
| CA2032303C (en) | 2002-03-19 |
| FI906140A0 (fi) | 1990-12-13 |
| PT96180A (pt) | 1991-09-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |
Free format text: LAPSED IN JUNE 2003 |