NO322016B1 - Anvendelse av utgangsmaterialer,fremgangsmate for hemisyntese av forbindelser og nye forbindelser - Google Patents

Anvendelse av utgangsmaterialer,fremgangsmate for hemisyntese av forbindelser og nye forbindelser Download PDF

Info

Publication number: NO322016B1
Authority: NO; Norway
Prior art keywords: group; compound; formula; ring; saframycin
Prior art date: 1999-05-14

Application number

NO20015547A

Other languages

English (en)

Norwegian (no)

Other versions

NO20015547D0 (no

NO20015547L (no

Inventor

Carmen Cuevas

Andres Francesch

Carolina Fernandez

Jose Luis Chicharro

Pilar Gallego

Maria Zarzuelo

Fernando De La Calle

Ignacio Manzanares

Marta Perez

Original Assignee

Pharma Mar Sa

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-05-14

Filing date

2001-11-13

Publication date

2006-08-07

1999-05-14 Priority claimed from GBGB9911345.8A external-priority patent/GB9911345D0/en

1999-08-02 Priority claimed from GBGB9918178.6A external-priority patent/GB9918178D0/en

1999-10-06 Priority claimed from GBGB9923632.5A external-priority patent/GB9923632D0/en

2000-01-17 Priority claimed from GB0001063A external-priority patent/GB0001063D0/en

2001-11-13 Application filed by Pharma Mar Sa filed Critical Pharma Mar Sa

2001-11-13 Publication of NO20015547D0 publication Critical patent/NO20015547D0/no

2002-01-14 Publication of NO20015547L publication Critical patent/NO20015547L/no

2006-08-07 Publication of NO322016B1 publication Critical patent/NO322016B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 185
238000000034 method Methods 0.000 title claims description 93
239000007858 starting material Substances 0.000 title claims description 30
238000006243 chemical reaction Methods 0.000 claims description 93
-1 hydroxymethylene group Chemical group 0.000 claims description 70
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical group O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 55
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 44
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
230000015572 biosynthetic process Effects 0.000 claims description 37
PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 claims description 34
229960000977 trabectedin Drugs 0.000 claims description 29
229930190585 Saframycin Natural products 0.000 claims description 26
125000000468 ketone group Chemical group 0.000 claims description 24
125000002252 acyl group Chemical group 0.000 claims description 23
XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 claims description 22
238000002360 preparation method Methods 0.000 claims description 21
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
GKUZBRIJGIGFKC-UHFFFAOYSA-N Safracin B Natural products OC1C(N2C)CC3=CC(C)=C(OC)C(O)=C3C2C(C2)N1C(CNC(=O)C(C)N)C1=C2C(=O)C(C)=C(OC)C1=O GKUZBRIJGIGFKC-UHFFFAOYSA-N 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 18
GKUZBRIJGIGFKC-XPXFATIHSA-N antibiotic em 5519 Chemical compound C([C@@H](N1C)[C@@H]2O)C3=CC(C)=C(OC)C(O)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O GKUZBRIJGIGFKC-XPXFATIHSA-N 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 18
125000003118 aryl group Chemical group 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 17
125000006239 protecting group Chemical group 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 claims description 16
238000003786 synthesis reaction Methods 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 15
230000008569 process Effects 0.000 claims description 15
239000003153 chemical reaction reagent Substances 0.000 claims description 11
229930194542 Keto Natural products 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
BHINEHROXMLHMV-BVRLQDJESA-N C([C@H](N1C)[C@@H]2C#N)C3=CC(C)=C(OC)C(O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O Chemical compound C([C@H](N1C)[C@@H]2C#N)C3=CC(C)=C(OC)C(O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O BHINEHROXMLHMV-BVRLQDJESA-N 0.000 claims description 9
229930188681 renieramycin Natural products 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
230000009467 reduction Effects 0.000 claims description 8
XRSKRSVTUVLURN-UHFFFAOYSA-N 1,3-benzodioxol-4-ol Chemical group OC1=CC=CC2=C1OCO2 XRSKRSVTUVLURN-UHFFFAOYSA-N 0.000 claims description 7
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
238000001212 derivatisation Methods 0.000 claims description 7
JNEGMBHBUAJRSX-SHUHUVMISA-N saframycin a Chemical compound C([C@H](N1C)[C@@H]2C#N)C(C(C(C)=C(OC)C3=O)=O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O JNEGMBHBUAJRSX-SHUHUVMISA-N 0.000 claims description 7
230000010933 acylation Effects 0.000 claims description 6
238000005917 acylation reaction Methods 0.000 claims description 6
LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
YMAUZYADYYYPHZ-UHFFFAOYSA-N Ecteinascidin 770 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(C#N)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C YMAUZYADYYYPHZ-UHFFFAOYSA-N 0.000 claims description 5
AZDDAJXLYMVMAW-FKTFMUQYSA-N Safracin A Natural products O=C(NC[C@@H]1N2[C@H]([C@@H]3N(C)[C@H](C2)Cc2c3c(O)c(OC)c(C)c2)CC=2C(=O)C(C)=C(OC)C(=O)C1=2)[C@@H](N)C AZDDAJXLYMVMAW-FKTFMUQYSA-N 0.000 claims description 5
AZDDAJXLYMVMAW-BVFBRMCBSA-N safracin a Chemical compound C([C@@H](N1C)C2)C3=CC(C)=C(OC)C(O)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O AZDDAJXLYMVMAW-BVFBRMCBSA-N 0.000 claims description 5
ZGVLLWBYFNMAOM-UHFFFAOYSA-N ac1l51xm Chemical compound C1C(N2C)CC(C(C(C)=C(OC)C3=O)=O)=C3C2C(C2)N1C(CNC(=O)C(C)O)C1=C2C(=O)C(C)=C(OC)C1=O ZGVLLWBYFNMAOM-UHFFFAOYSA-N 0.000 claims description 4
125000000524 functional group Chemical group 0.000 claims description 4
230000000269 nucleophilic effect Effects 0.000 claims description 4
LMKHFHFSEWJQID-UHFFFAOYSA-N Saframycin B Natural products COC1=C(C)C(=O)C2=C(CC3C4N(C)C(CN3C2CNC(=O)C(=O)C)CC5=C4C(=O)C(=C(C)C5=O)OC)C1=O LMKHFHFSEWJQID-UHFFFAOYSA-N 0.000 claims description 3
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 3
239000003054 catalyst Substances 0.000 claims description 3
125000002697 cystyl group Chemical group 0.000 claims description 3
FKBKETJRCKZDAM-SDBDLDFRSA-N decyano-saframycin a Chemical compound C([C@@H](N1C)[C@@H]2O)C(C(C(C)=C(OC)C3=O)=O)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O FKBKETJRCKZDAM-SDBDLDFRSA-N 0.000 claims description 3
238000006073 displacement reaction Methods 0.000 claims description 3
BGFXHQYUWCGGLL-QWIBJBKUSA-N ecteinascidin 770 Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](C#N)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 BGFXHQYUWCGGLL-QWIBJBKUSA-N 0.000 claims description 3
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 3
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 3
125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 3
229950003188 isovaleryl diethylamide Drugs 0.000 claims description 3
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000000405 phenylalanyl group Chemical group 0.000 claims description 3
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
KOHPLTGVBZMVDW-BBTHKVSRSA-N saframycin b Chemical compound C([C@@H](N1C)C2)C(C(C(C)=C(OC)C3=O)=O)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O KOHPLTGVBZMVDW-BBTHKVSRSA-N 0.000 claims description 3
GATZXGIUISULHU-WDDJOWQOSA-N saframycin r Chemical group C([C@@H](N1C)[C@@H]2C#N)C3=C(O)C(C)=C(OC)C(OC(=O)CO)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O GATZXGIUISULHU-WDDJOWQOSA-N 0.000 claims description 3
238000006467 substitution reaction Methods 0.000 claims description 3
QSLZNGPMBOCIAZ-QSNGQZDXSA-N 113036-78-5 Chemical compound C12=C(O)C(OC)=C(C)C(O)=C2[C@H](OC)[C@H]2N(C)[C@@H]1[C@H](CC=1C(C(C)=C(OC)C(=O)C=1[C@@H]1CNC(=O)[C@H](C)N)=O)N1[C@H]2O QSLZNGPMBOCIAZ-QSNGQZDXSA-N 0.000 claims description 2
HBULEGBKIIJRCH-UHFFFAOYSA-N Renieramycin B Natural products O=C1C(C)=C(OC)C(=O)C2=C1C(OCC)C1CN3C(COC(=O)C(C)=CC)C(C(=O)C(OC)=C(C)C4=O)=C4CC3C2N1C HBULEGBKIIJRCH-UHFFFAOYSA-N 0.000 claims description 2
HHQBCXAQIYVYGF-UHFFFAOYSA-N Renieramycin D Natural products O=C1C(C)=C(OC)C(=O)C2=C1C(OCC)C1C(=O)N3C(COC(=O)C(C)=CC)C(C(=O)C(OC)=C(C)C4=O)=C4CC3C2N1C HHQBCXAQIYVYGF-UHFFFAOYSA-N 0.000 claims description 2
BGHIUZDGPHSOIT-UHFFFAOYSA-N Renieramycin E Natural products OC1C(N2C)CC(C(C(C)=C(OC)C3=O)=O)=C3C2C(C2)N1C(COC(=O)C(C)=CC)C1=C2C(=O)C(C)=C(OC)C1=O BGHIUZDGPHSOIT-UHFFFAOYSA-N 0.000 claims description 2
WVBLIKAXDJHLIE-UHFFFAOYSA-N Saframycin C Natural products COC1C2CN3C(CC4=C(C3CNC(=O)C(=O)C)C(=O)C(=C(OC)C4=O)C)C(N2C)C5=C1C(=O)C(=C(OC)C5=O)C WVBLIKAXDJHLIE-UHFFFAOYSA-N 0.000 claims description 2
YQQUMADRNAOVHP-UHFFFAOYSA-N Saframycin G Natural products CN1C(C2C#N)C(O)C(C(C(C)=C(OC)C3=O)=O)=C3C1C(C1)N2C(CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O YQQUMADRNAOVHP-UHFFFAOYSA-N 0.000 claims description 2
QSLZNGPMBOCIAZ-UHFFFAOYSA-N Saframycin Mx 1 Natural products C12=C(O)C(OC)=C(C)C(O)=C2C(OC)C2N(C)C1C(CC=1C(C(C)=C(OC)C(=O)C=1C1CNC(=O)C(C)N)=O)N1C2O QSLZNGPMBOCIAZ-UHFFFAOYSA-N 0.000 claims description 2
UFWYPWFCNWILJC-UHFFFAOYSA-N Saframycin Mx 2 Natural products COC1C2CN3C(CC4=C(C3CNC(=O)C(C)N)C(=O)C(=C(C)C4=O)OC)C(N2C)c5c(O)c(OC)c(C)c(O)c15 UFWYPWFCNWILJC-UHFFFAOYSA-N 0.000 claims description 2
KLKJKXQSKPPFSJ-UHFFFAOYSA-N Saframycin Y3 Natural products CN1C(C2C#N)CC(C(C(C)=C(OC)C3=O)=O)=C3C1C(C1)N2C(CNC(=O)C(C)N)C2=C1C(=O)C(C)=C(OC)C2=O KLKJKXQSKPPFSJ-UHFFFAOYSA-N 0.000 claims description 2
DULAUWVTCHNVOZ-UHFFFAOYSA-N Saframycin YD-2 Natural products CN1C(C2C#N)CC(C(C(C)=C(OC)C3=O)=O)=C3C1C(C1)N2C(CNC(=O)CN)C2=C1C(=O)C(C)=C(OC)C2=O DULAUWVTCHNVOZ-UHFFFAOYSA-N 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
125000001165 hydrophobic group Chemical group 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
VHXCHPIQWWKYPI-UHFFFAOYSA-N renieramycin C Natural products CN1C(C2=O)C(O)C(C(C(C)=C(OC)C3=O)=O)=C3C1C(C1)N2C(COC(=O)C(C)=CC)C2=C1C(=O)C(C)=C(OC)C2=O VHXCHPIQWWKYPI-UHFFFAOYSA-N 0.000 claims description 2
JIJFDUYXCLTCFT-FZLBTGRLSA-N saframycin c Chemical compound O=C1C(C)=C(OC)C(=O)C2=C1[C@H](OC)[C@H]1CN3[C@@H](CNC(=O)C(C)=O)C(C(=O)C(OC)=C(C)C4=O)=C4C[C@H]3[C@@H]2N1C JIJFDUYXCLTCFT-FZLBTGRLSA-N 0.000 claims description 2
JRGSNFZUTBSLSG-ZKNHNOBHSA-N saframycin d Chemical compound C1([C@@H]([C@@H]2C3)N4C)=C(O)C(OC)=C(C)C(O)=C1C(=O)[C@@H]4CN2[C@@H](CNC(=O)C(C)=O)C1=C3C(=O)C(C)=C(OC)C1=O JRGSNFZUTBSLSG-ZKNHNOBHSA-N 0.000 claims description 2
WDQZQIAZHSHOFD-UHFFFAOYSA-N saframycin f Chemical compound CN1C(C2C#N)C(=O)C3=C(O)C(C)=C(OC)C(O)=C3C1C(C1)N2C(CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O WDQZQIAZHSHOFD-UHFFFAOYSA-N 0.000 claims description 2
YQQUMADRNAOVHP-SEBJRLBMSA-N saframycin g Chemical compound O=C1C(OC)=C(C)C(=O)C([C@H](O)[C@H](N2C)C3C#N)=C1[C@@H]2[C@H](C1)N3[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O YQQUMADRNAOVHP-SEBJRLBMSA-N 0.000 claims description 2
PYOFDRKUKHPATO-JLUOOAMSSA-N saframycin h Chemical compound C([C@H](N1C)C2C#N)C(C(C(C)=C(OC)C3=O)=O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)(O)CC(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O PYOFDRKUKHPATO-JLUOOAMSSA-N 0.000 claims description 2
KLKJKXQSKPPFSJ-XFPFBUNZSA-N saframycin y3 Chemical compound C([C@@H](N1C)C2C#N)C(C(C(C)=C(OC)C3=O)=O)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O KLKJKXQSKPPFSJ-XFPFBUNZSA-N 0.000 claims description 2
DULAUWVTCHNVOZ-FSCDNRMKSA-N saframycin-yd2 Chemical compound C([C@@H](N1C)C2C#N)C(C(C(C)=C(OC)C3=O)=O)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)CN)C2=C1C(=O)C(C)=C(OC)C2=O DULAUWVTCHNVOZ-FSCDNRMKSA-N 0.000 claims description 2
125000001980 alanyl group Chemical group 0.000 claims 3
XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims 1
239000002253 acid Substances 0.000 claims 1
125000004744 butyloxycarbonyl group Chemical group 0.000 claims 1
125000001939 glutaminyl group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
125000001998 leucyl group Chemical group 0.000 claims 1
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125000002073 methionyl group Chemical group 0.000 claims 1
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150000003573 thiols Chemical group 0.000 claims 1
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229910052938 sodium sulfate Inorganic materials 0.000 description 48
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CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
229960004799 tryptophan Drugs 0.000 description 1
239000003744 tubulin modulator Substances 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
238000009489 vacuum treatment Methods 0.000 description 1
229960004295 valine Drugs 0.000 description 1
239000004474 valine Substances 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Steroid Compounds (AREA)
Saccharide Compounds (AREA)

NO20015547A 1999-05-14 2001-11-13 Anvendelse av utgangsmaterialer,fremgangsmate for hemisyntese av forbindelser og nye forbindelser NO322016B1 (no)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GBGB9911345.8A GB9911345D0 (pt)	1999-05-14	1999-05-14
GBGB9918178.6A GB9918178D0 (en)	2000-05-15	1999-08-02	Synthetic methods
GBGB9923632.5A GB9923632D0 (en)	1999-10-06	1999-10-06	Hemisynthetic process towards ecteinascidin and phtalscidin compounds
GB0001063A GB0001063D0 (en)	2000-01-17	2000-01-17	Hemisynthetic process towards ecteinascidin and phtalascidin
PCT/GB2000/001852 WO2000069862A2 (en)	1999-05-14	2000-05-15	Hemisynthetic method and intermediates thereof

Publications (3)

Publication Number	Publication Date
NO20015547D0 NO20015547D0 (no)	2001-11-13
NO20015547L NO20015547L (no)	2002-01-14
NO322016B1 true NO322016B1 (no)	2006-08-07

Family

ID=42632476

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20015547A NO322016B1 (no)	1999-05-14	2001-11-13	Anvendelse av utgangsmaterialer,fremgangsmate for hemisyntese av forbindelser og nye forbindelser
NO20025186A NO328301B1 (no)	1999-05-14	2002-10-29	Fremgangsmate for syntese av en ecteinascidinforbindelse

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20025186A NO328301B1 (no)	1999-05-14	2002-10-29	Fremgangsmate for syntese av en ecteinascidinforbindelse

Country Status (29)

Country	Link
US (3)	US7241892B1 (pt)
EP (1)	EP1185536B1 (pt)
JP (1)	JP4445136B2 (pt)
KR (1)	KR100834601B1 (pt)
CN (3)	CN1229382C (pt)
AR (1)	AR035842A1 (pt)
AT (1)	ATE283273T1 (pt)
AU (2)	AU775580B2 (pt)
BG (1)	BG65896B1 (pt)
BR (3)	BRPI0010559B8 (pt)
CA (2)	CA2372058C (pt)
CY (1)	CY1108095T1 (pt)
CZ (3)	CZ303536B6 (pt)
DE (1)	DE60016209T2 (pt)
DK (1)	DK1185536T3 (pt)
ES (2)	ES2233367T3 (pt)
HU (1)	HU230646B1 (pt)
MX (1)	MXPA01011631A (pt)
MY (1)	MY130271A (pt)
NO (2)	NO322016B1 (pt)
NZ (1)	NZ515424A (pt)
PL (1)	PL226890B1 (pt)
PT (1)	PT1185536E (pt)
RU (1)	RU2237063C9 (pt)
SI (2)	SI1185536T1 (pt)
SK (2)	SK287835B6 (pt)
TR (1)	TR200103273T2 (pt)
UA (1)	UA75333C2 (pt)
WO (3)	WO2000069862A2 (pt)

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GB0522082D0 (en)	2005-10-31	2005-12-07	Pharma Mar Sa	Formulations
KR100712667B1 (ko)	2006-04-11	2007-05-02	재단법인서울대학교산학협력재단	신규한 디아자 헤테로고리 유도체 및 그의 고체상 제조방법
GB0708691D0 (en) *	2007-05-04	2007-06-13	Pharma Mar Sa	Anticancer treatments a
US20090076017A1 (en) *	2007-09-15	2009-03-19	Protia, Llc	Deuterium-enriched trabectedin
WO2009050303A1 (en) *	2007-10-19	2009-04-23	Pharma Mar, S.A.	Prognostic molecular markers for et-743 treatment
EP2307003A2 (en) *	2008-05-16	2011-04-13	Pharma Mar S.A.	Combination therapy with pm00104 and another antitumor agent
AU2009248039B2 (en) *	2008-05-16	2014-07-31	Pharma Mar, S.A.	Multiple myeloma treatments
WO2011048210A1 (en)	2009-10-22	2011-04-28	Pharma Mar, S.A.	PDGFR-α AS RESPONSE MARKER FOR PM00104 TREATMENT
WO2011147828A1 (en)	2010-05-25	2011-12-01	Pharma Mar, S.A.	Synthetic process for the manufacture of ecteinascidin compounds
EP2786755A3 (en)	2010-11-12	2014-10-29	Pharma Mar S.A.	Combination therapy with an antitumor alkaloid
LT3615544T (lt)	2017-04-27	2023-05-10	Pharma Mar S.A.	Priešnavikiniai junginiai
CN107739387B (zh) *	2017-10-16	2020-01-03	上海皓元生物医药科技有限公司	一种制备曲贝替定的关键中间体化合物的方法
CN109912629B (zh) *	2017-12-13	2021-12-24	浙江中科创越药业有限公司	天然产物Trabectedin的制备
TWI824043B (zh)	2018-10-25	2023-12-01	西班牙商瑪製藥股份有限公司	藥物抗體共軛物
CN111518110B (zh) *	2019-02-01	2023-11-03	博瑞生物医药（苏州）股份有限公司	一种海鞘素化合物及其中间体的制备方法
CN111620792B (zh) *	2019-02-28	2023-01-03	兰州大学	一种n,n-二取代氰基甲酰胺的合成方法
CA3158733A1 (en)	2019-11-21	2021-05-27	Pilar Calvo	Methods of treating small cell lung cancer with lurbinectedin formulations
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2000
- 2000-05-12 MY MYPI20002078A patent/MY130271A/en unknown
- 2000-05-12 AR ARP000102308A patent/AR035842A1/es active IP Right Grant
- 2000-05-15 EP EP00927582A patent/EP1185536B1/en not_active Expired - Lifetime
- 2000-05-15 SI SI200030599T patent/SI1185536T1/xx unknown
- 2000-05-15 WO PCT/GB2000/001852 patent/WO2000069862A2/en not_active Ceased
- 2000-05-15 PL PL353002A patent/PL226890B1/pl unknown
- 2000-05-15 DE DE60016209T patent/DE60016209T2/de not_active Expired - Lifetime
- 2000-05-15 ES ES00927582T patent/ES2233367T3/es not_active Expired - Lifetime
- 2000-05-15 HU HU0201188A patent/HU230646B1/hu unknown
- 2000-05-15 US US09/979,404 patent/US7241892B1/en not_active Expired - Lifetime
- 2000-05-15 RU RU2001133386/04A patent/RU2237063C9/ru active
- 2000-05-15 MX MXPA01011631A patent/MXPA01011631A/es active IP Right Grant
- 2000-05-15 JP JP2000618279A patent/JP4445136B2/ja not_active Expired - Lifetime
- 2000-05-15 UA UA2001128605A patent/UA75333C2/uk unknown
- 2000-05-15 PT PT00927582T patent/PT1185536E/pt unknown
- 2000-05-15 BR BRPI0010559A patent/BRPI0010559B8/pt not_active IP Right Cessation
- 2000-05-15 NZ NZ515424A patent/NZ515424A/en not_active IP Right Cessation
- 2000-05-15 TR TR2001/03273T patent/TR200103273T2/xx unknown
- 2000-05-15 AT AT00927582T patent/ATE283273T1/de active
- 2000-05-15 CZ CZ20014102A patent/CZ303536B6/cs not_active IP Right Cessation
- 2000-05-15 DK DK00927582T patent/DK1185536T3/da active
- 2000-05-15 AU AU45973/00A patent/AU775580B2/en not_active Expired
- 2000-05-15 CA CA2372058A patent/CA2372058C/en not_active Expired - Lifetime
- 2000-05-15 KR KR1020017014551A patent/KR100834601B1/ko not_active Expired - Lifetime
- 2000-05-15 CN CNB008100829A patent/CN1229382C/zh not_active Expired - Lifetime
- 2000-05-15 SK SK1650-2001A patent/SK287835B6/sk not_active IP Right Cessation
2001
- 2001-05-15 CZ CZ2002-3751A patent/CZ304973B6/cs not_active IP Right Cessation
- 2001-05-15 BR BR0110443-8 patent/BRPI0110443B8/pt not_active IP Right Cessation
- 2001-05-15 CN CNB018120431A patent/CN100475822C/zh not_active Expired - Lifetime
- 2001-05-15 CZ CZ2002-3746A patent/CZ304966B6/cs not_active IP Right Cessation
- 2001-05-15 BR BR0110801-8 patent/BRPI0110801B8/pt not_active IP Right Cessation
- 2001-05-15 AU AU5649601A patent/AU5649601A/xx active Pending
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- 2001-05-15 ES ES01929813T patent/ES2231486T3/es not_active Expired - Lifetime
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- 2001-05-15 CN CNB018127460A patent/CN1211386C/zh not_active Expired - Lifetime
- 2001-05-15 US US10/257,856 patent/US20040002602A1/en not_active Abandoned
- 2001-05-15 WO PCT/GB2001/002110 patent/WO2001087894A1/en not_active Ceased
- 2001-05-15 SI SI200130399T patent/SI1287004T1/sl unknown
- 2001-05-15 SK SK1527-2002A patent/SK287879B6/sk not_active IP Right Cessation
- 2001-11-13 NO NO20015547A patent/NO322016B1/no not_active IP Right Cessation
2002
- 2002-10-29 NO NO20025186A patent/NO328301B1/no not_active IP Right Cessation
- 2002-11-20 BG BG107301A patent/BG65896B1/bg unknown
2007
- 2007-07-09 US US11/774,890 patent/US7524956B2/en not_active Expired - Fee Related
- 2007-10-29 CY CY20071101392T patent/CY1108095T1/el unknown

Also Published As

Publication number	Publication date
SK287835B6 (sk)	2011-12-05
CZ20023751A3 (en)	2004-05-12
BRPI0110443B1 (pt)	2018-06-26
CZ304966B6 (cs)	2015-02-18
WO2001087894A1 (en)	2001-11-22
NZ515424A (en)	2004-06-25
CN1211386C (zh)	2005-07-20
EP1185536B1 (en)	2004-11-24
NO20025186D0 (no)	2002-10-29
DK1185536T3 (da)	2005-04-04
JP2002544280A (ja)	2002-12-24
CA2372058A1 (en)	2000-11-23
CN1360588A (zh)	2002-07-24
NO20015547D0 (no)	2001-11-13
US7241892B1 (en)	2007-07-10
PL226890B1 (pl)	2017-09-29
WO2001087895A1 (en)	2001-11-22
PL353002A1 (en)	2003-09-22
SI1185536T1 (en)	2005-06-30
CA2372058C (en)	2010-10-26
RU2237063C2 (ru)	2004-09-27
EP1185536A2 (en)	2002-03-13
MXPA01011631A (es)	2002-07-30
HU230646B1 (hu)	2017-05-29
CZ20023746A3 (cs)	2003-04-16
NO20015547L (no)	2002-01-14
WO2000069862A2 (en)	2000-11-23
MY130271A (en)	2007-06-29
US7524956B2 (en)	2009-04-28
KR100834601B1 (ko)	2008-06-02
UA75333C2 (uk)	2006-04-17
CA2406095A1 (en)	2001-11-22
NO20025186L (no)	2003-01-14
SK16502001A3 (sk)	2002-06-04
CZ20014102A3 (cs)	2002-06-12
ATE283273T1 (de)	2004-12-15
BG107301A (bg)	2003-07-31
BRPI0110801B8 (pt)	2021-05-25
CN1440414A (zh)	2003-09-03
SK15272002A3 (sk)	2003-06-03
US20080045713A1 (en)	2008-02-21
CN1229382C (zh)	2005-11-30
AU5649601A (en)	2001-11-26
CN1441805A (zh)	2003-09-10
BRPI0110801B1 (pt)	2018-02-27
CY1108095T1 (el)	2014-02-12
AR035842A1 (es)	2004-07-21
CA2406095C (en)	2010-02-16
RU2237063C9 (ru)	2008-10-10
NO328301B1 (no)	2010-01-25
CZ303536B6 (cs)	2012-11-21
ES2233367T3 (es)	2005-06-16
DE60016209D1 (de)	2004-12-30
TR200103273T2 (tr)	2002-04-22
BR0110801A (pt)	2003-02-11
AU4597300A (en)	2000-12-05
BG65896B1 (bg)	2010-04-30
HK1047432A1 (en)	2003-02-21
CN100475822C (zh)	2009-04-08
DE60016209T2 (de)	2005-12-15
AU775580B2 (en)	2004-08-05
BRPI0010559B8 (pt)	2021-05-25
BRPI0110443B8 (pt)	2021-05-25
SK287879B6 (sk)	2012-02-03
KR20020021636A (ko)	2002-03-21
BRPI0010559B1 (pt)	2016-08-30
ES2231486T3 (es)	2005-05-16
WO2000069862A3 (en)	2001-03-22
SI1287004T1 (sl)	2005-12-31
BR0010559A (pt)	2002-07-02
US20040002602A1 (en)	2004-01-01
BR0110443A (pt)	2003-04-08
CZ304973B6 (cs)	2015-02-25
HUP0201188A2 (en)	2002-07-29
JP4445136B2 (ja)	2010-04-07
PT1185536E (pt)	2005-04-29

Legal Events

Date	Code	Title	Description
2020-06-08	MK1K	Patent expired

Publication	Publication Date	Title
EP1185536B1 (en)	2004-11-24	Hemisynthetic method and intermediates thereof
US7420051B2 (en)	2008-09-02	Synthetic process for the manufacture of an ecteinaschidin compound
EP1287004B1 (en)	2005-07-27	Synthetic process for the manufacture of an ecteinascidin compound
AU2001256496A1 (en)	2002-02-14	Synthetic process for the manufacture of an ecteinascidin compound
NO329561B1 (no)	2010-11-15	Forbindelser som er analoger av ET-743, farmasoytiske preparater som omfatter en slik forbindelse, og anvendelse av forbindelsene til fremstilling av farmasoytiske preparater for anvendelse ved behandling av tumorer
BG106216A (bg)	2002-08-30	Полусинтетичен метод и нови съединения
HK1050193B (en)	2006-03-03	Synthetic process for the manufacture of an ecteinascidin compound
IL152125A (en)	2008-04-13	Process for the manufacture of ecteinascidin derivatives