DD299067A5 - Verfahren zur herstellung von zwischenprodukten fuer epipodophyllotoxinglucosid-4'-phosphat-derivate - Google Patents

Verfahren zur herstellung von zwischenprodukten fuer epipodophyllotoxinglucosid-4'-phosphat-derivate Download PDF

Info

Publication number: DD299067A5
Authority: DD; German Democratic Republic
Prior art keywords: etoposide; phosphate; compound; general formula; mmol
Prior art date: 1987-08-04

Application number

DD88326917A

Other languages

German (de)

English (en)

Inventor

Mark G Saulnier

Peter D Senter

John F Kadow

Original Assignee

��`��@��@��k��

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.)

1987-08-04

Filing date

1988-08-03

Publication date

1992-03-26

1988-08-03 Application filed by ��`��@��@��k�� filed Critical ��`��@��@��k��

1992-03-26 Publication of DD299067A5 publication Critical patent/DD299067A5/de

Links

238000004519 manufacturing process Methods 0.000 title description 2
239000013067 intermediate product Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 46
238000000034 method Methods 0.000 claims abstract description 17
238000002360 preparation method Methods 0.000 claims abstract description 13
239000000543 intermediate Substances 0.000 claims abstract description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 5
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
229910052717 sulfur Chemical group 0.000 claims description 3
239000011593 sulfur Chemical group 0.000 claims description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
150000001721 carbon Chemical group 0.000 claims description 2
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125000001475 halogen functional group Chemical group 0.000 claims 1
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NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 abstract description 8
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-1 epipodophyllotoxin glucoside Chemical class 0.000 description 20
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LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
230000000865 phosphorylative effect Effects 0.000 description 6
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FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 5
BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 5
125000000217 alkyl group Chemical group 0.000 description 5
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238000003818 flash chromatography Methods 0.000 description 5
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150000003013 phosphoric acid derivatives Chemical class 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 description 4
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150000001768 cations Chemical class 0.000 description 4
238000010828 elution Methods 0.000 description 4
LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 4
229910052698 phosphorus Inorganic materials 0.000 description 4
239000011574 phosphorus Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
FOVRGQUEGRCWPD-UHFFFAOYSA-N (5aR)-9t-beta-D-Glucopyranosyloxy-5t-(4-hydroxy-3,5-dimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol-6-on Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(OC3C(C(O)C(O)C(CO)O3)O)C3C2C(OC3)=O)=C1 FOVRGQUEGRCWPD-UHFFFAOYSA-N 0.000 description 3
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238000004458 analytical method Methods 0.000 description 3
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ITVPBBDAZKBMRP-UHFFFAOYSA-N chloro-dioxido-oxo-$l^{5}-phosphane;hydron Chemical class OP(O)(Cl)=O ITVPBBDAZKBMRP-UHFFFAOYSA-N 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 2
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DJMIKAGANCZWLL-UHFFFAOYSA-N dihydroxy hydrogen phosphate Chemical compound OOP(O)(=O)OO DJMIKAGANCZWLL-UHFFFAOYSA-N 0.000 description 2
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125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
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WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
102100035703 Prostatic acid phosphatase Human genes 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
150000001342 alkaline earth metals Chemical group 0.000 description 1
125000005236 alkanoylamino group Chemical group 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000003282 alkyl amino group 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
229910021529 ammonia Inorganic materials 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
229910052792 caesium Inorganic materials 0.000 description 1
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000003729 cation exchange resin Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000013256 coordination polymer Substances 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
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230000003247 decreasing effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
239000012954 diazonium Substances 0.000 description 1
OOFVSLAKBNBEEH-UHFFFAOYSA-N dichloro-hydroxy-sulfanylidene-$l^{5}-phosphane Chemical compound OP(Cl)(Cl)=S OOFVSLAKBNBEEH-UHFFFAOYSA-N 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
239000003118 drug derivative Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
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150000002148 esters Chemical class 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
210000003608 fece Anatomy 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000008187 granular material Substances 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000002054 inoculum Substances 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
230000002601 intratumoral effect Effects 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
229930013686 lignan Natural products 0.000 description 1
150000005692 lignans Chemical class 0.000 description 1
235000009408 lignans Nutrition 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
208000025113 myeloid leukemia Diseases 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
125000001477 organic nitrogen group Chemical group 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
JBPIOCKLCIFHIX-UHFFFAOYSA-N oxo-[2-[[3-[oxo(sulfido)azaniumyl]-5-sulfanyl-4-sulfanylidene-1H-pyridin-2-yl]disulfanyl]-5-sulfanyl-4-sulfanylidene-1H-pyridin-3-yl]-sulfidoazanium Chemical compound [O-][N+](=S)C1=C(S)C(S)=CN=C1SSC1=NC=C(S)C(S)=C1[N+]([O-])=S JBPIOCKLCIFHIX-UHFFFAOYSA-N 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
125000005541 phosphonamide group Chemical group 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
150000008299 phosphorodiamidates Chemical class 0.000 description 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
108010043671 prostatic acid phosphatase Proteins 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
235000019515 salmon Nutrition 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
230000002381 testicular Effects 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Mechanical Coupling Of Light Guides (AREA)
Cable Accessories (AREA)

DD88326917A 1987-08-04 1988-08-03 Verfahren zur herstellung von zwischenprodukten fuer epipodophyllotoxinglucosid-4'-phosphat-derivate DD299067A5 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US8149387A	1987-08-04	1987-08-04
US07/199,731 US4904768A (en)	1987-08-04	1988-05-27	Epipodophyllotoxin glucoside 4'-phosphate derivatives

Publications (1)

Publication Number	Publication Date
DD299067A5 true DD299067A5 (de)	1992-03-26

Family

ID=26765636

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
DD88326917A DD299067A5 (de)	1987-08-04	1988-08-03	Verfahren zur herstellung von zwischenprodukten fuer epipodophyllotoxinglucosid-4'-phosphat-derivate
DD88318652A DD274423A5 (de)	1987-08-04	1988-08-03	Verfahren zur herstellung von epipodophyllotoxinglucosid-4'-phosphat derivaten

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
DD88318652A DD274423A5 (de)	1987-08-04	1988-08-03	Verfahren zur herstellung von epipodophyllotoxinglucosid-4'-phosphat derivaten

Country Status (34)

Country	Link
US (3)	US4904768A (fr)
JP (1)	JPH0699465B2 (fr)
KR (1)	KR900006230B1 (fr)
CN (1)	CN1027169C (fr)
AT (1)	AT398974B (fr)
BE (1)	BE1002982A4 (fr)
CA (1)	CA1310637C (fr)
CH (1)	CH676716A5 (fr)
CY (1)	CY1625A (fr)
CZ (1)	CZ286893B6 (fr)
DD (2)	DD299067A5 (fr)
DE (1)	DE3826562A1 (fr)
DK (2)	DK169344B1 (fr)
ES (1)	ES2010775A6 (fr)
FI (1)	FI87790C (fr)
FR (1)	FR2622193B1 (fr)
GB (1)	GB2207674B (fr)
GR (1)	GR1000490B (fr)
HK (1)	HK6392A (fr)
HU (3)	HU202547B (fr)
IE (1)	IE61040B1 (fr)
IL (1)	IL87290A (fr)
IT (1)	IT1226825B (fr)
LU (2)	LU87290A1 (fr)
MX (1)	MX173843B (fr)
MY (1)	MY104321A (fr)
NL (2)	NL192683C (fr)
NO (4)	NO170284C (fr)
NZ (1)	NZ225615A (fr)
PT (1)	PT88186B (fr)
SE (1)	SE502214C2 (fr)
SG (1)	SG101291G (fr)
SK (1)	SK541288A3 (fr)
YU (3)	YU143688A (fr)

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BR112014028420A2 (pt)	2012-05-16	2017-09-19	Novartis Ag	regime de dosagem para um inibidor de quinase pi-3
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PL3076969T3 (pl)	2013-12-06	2022-01-17	Novartis Ag	Schemat dawkowania selektywnego inhibitora 3-kinazy fosfatydynozytolu alfa-izoformy
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MX2018005298A (es)	2015-11-02	2018-06-22	Novartis Ag	Regimen de dosificacion para un inhibidor de fosfatidilinositol 3-quinasa.
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1988
- 1988-05-27 US US07/199,731 patent/US4904768A/en not_active Ceased
- 1988-07-21 MY MYPI88000819A patent/MY104321A/en unknown
- 1988-07-22 LU LU87290A patent/LU87290A1/fr active Protection Beyond IP Right Term
- 1988-07-25 YU YU01436/88A patent/YU143688A/xx unknown
- 1988-07-26 NO NO883299A patent/NO170284C/no not_active IP Right Cessation
- 1988-07-28 IT IT8821535A patent/IT1226825B/it active
- 1988-07-29 FR FR8810258A patent/FR2622193B1/fr not_active Expired - Lifetime
- 1988-07-29 NZ NZ225615A patent/NZ225615A/en unknown
- 1988-08-01 FI FI883596A patent/FI87790C/fi not_active IP Right Cessation
- 1988-08-01 IL IL87290A patent/IL87290A/xx not_active IP Right Cessation
- 1988-08-02 SK SK5412-88A patent/SK541288A3/sk unknown
- 1988-08-02 CZ CS19885412A patent/CZ286893B6/cs not_active IP Right Cessation
- 1988-08-03 HU HU884081A patent/HU202547B/hu unknown
- 1988-08-03 DD DD88326917A patent/DD299067A5/de unknown
- 1988-08-03 HU HU905862A patent/HU208147B/hu unknown
- 1988-08-03 ES ES8802434A patent/ES2010775A6/es not_active Expired
- 1988-08-03 DD DD88318652A patent/DD274423A5/de unknown
- 1988-08-03 PT PT88186A patent/PT88186B/pt not_active IP Right Cessation
- 1988-08-03 KR KR1019880009910A patent/KR900006230B1/ko not_active Expired
- 1988-08-03 NL NL8801934A patent/NL192683C/nl not_active IP Right Cessation
- 1988-08-03 AT AT0195588A patent/AT398974B/de active
- 1988-08-03 BE BE8800898A patent/BE1002982A4/fr not_active IP Right Cessation
- 1988-08-03 DK DK434088A patent/DK169344B1/da not_active IP Right Cessation
- 1988-08-03 JP JP63194307A patent/JPH0699465B2/ja not_active Expired - Lifetime
- 1988-08-03 IE IE237888A patent/IE61040B1/en not_active IP Right Cessation
- 1988-08-03 GB GB8818462A patent/GB2207674B/en not_active Expired - Lifetime
- 1988-08-03 SE SE8802815A patent/SE502214C2/sv not_active IP Right Cessation
- 1988-08-04 DE DE3826562A patent/DE3826562A1/de active Granted
- 1988-08-04 CA CA000573861A patent/CA1310637C/fr not_active Expired - Lifetime
- 1988-08-04 GR GR880100512A patent/GR1000490B/el not_active IP Right Cessation
- 1988-08-04 CH CH2962/88A patent/CH676716A5/de not_active IP Right Cessation
1989
- 1989-12-14 US US07/450,718 patent/US5041424A/en not_active Expired - Lifetime
1990
- 1990-01-19 YU YU00104/90A patent/YU10490A/xx unknown
- 1990-01-19 YU YU00103/90A patent/YU10390A/xx unknown
1991
- 1991-10-30 CN CN91108384A patent/CN1027169C/zh not_active Expired - Lifetime
- 1991-11-29 SG SG1012/91A patent/SG101291G/en unknown
1992
- 1992-01-16 HK HK63/92A patent/HK6392A/xx not_active IP Right Cessation
- 1992-01-22 NO NO920277A patent/NO920277D0/no unknown
- 1992-01-31 DK DK011992A patent/DK11992A/da not_active Application Discontinuation
- 1992-02-20 NO NO920665A patent/NO172440C/no not_active IP Right Cessation
- 1992-06-12 MX MX9202851A patent/MX173843B/es unknown
- 1992-07-10 CY CY1625A patent/CY1625A/en unknown
1994
- 1994-04-19 US US08/229,659 patent/USRE35524E/en not_active Expired - Lifetime
1995
- 1995-06-22 HU HU95P/P00387P patent/HU211960A9/hu unknown
1997
- 1997-09-24 LU LU90138C patent/LU90138I2/fr unknown
- 1997-12-05 NL NL970042C patent/NL970042I1/nl unknown
1998
- 1998-01-14 NO NO1998002C patent/NO1998002I1/no unknown

Also Published As

Publication number	Publication date
NO920277D0 (no)	1992-01-22
CZ286893B6 (cs)	2000-07-12
SK279325B6 (sk)	1998-10-07
PT88186A (pt)	1989-06-30
FR2622193B1 (fr)	1993-12-17
FR2622193A1 (fr)	1989-04-28
GR880100512A (en)	1989-05-25
NZ225615A (en)	1991-06-25
PT88186B (pt)	1995-07-03
BE1002982A4 (fr)	1991-10-15
IT8821535A0 (it)	1988-07-28
IL87290A (en)	1993-01-31
CN1027169C (zh)	1994-12-28
NO883299L (no)	1989-02-24
SG101291G (en)	1992-01-17
IT1226825B (it)	1991-02-19
CY1625A (en)	1992-07-10
HUT47303A (en)	1989-02-28
KR900006230B1 (ko)	1990-08-27
GB2207674B (en)	1991-09-11
US4904768A (en)	1990-02-27
GR1000490B (el)	1992-07-30
AU610619B2 (en)	1991-05-23
FI87790B (fi)	1992-11-13
YU10490A (en)	1990-06-30
AT398974B (de)	1995-02-27
DK11992D0 (da)	1992-01-31
MY104321A (en)	1994-03-31
JPH01100188A (ja)	1989-04-18
DK434088A (da)	1989-02-05
NL192683B (fr)	1997-08-01
AU2030688A (en)	1989-06-08
DK434088D0 (da)	1988-08-03
NO170284C (no)	1992-09-30
DD274423A5 (de)	1989-12-20
YU143688A (en)	1990-04-30
IE882378L (en)	1989-02-04
DK11992A (da)	1992-01-31
ATA195588A (de)	1994-07-15
SE502214C2 (sv)	1995-09-18
ES2010775A6 (es)	1989-12-01
LU90138I2 (fr)	1997-11-26
NO920665D0 (no)	1992-02-20
IE61040B1 (en)	1994-09-07
NL192683C (nl)	1997-12-02
FI883596A7 (fi)	1989-02-05
USRE35524E (en)	1997-06-03
NO172440B (no)	1993-04-13
IL87290A0 (en)	1989-01-31
DE3826562A1 (de)	1989-02-16
CH676716A5 (fr)	1991-02-28
NO170284B (no)	1992-06-22
HK6392A (en)	1992-01-17
JPH0699465B2 (ja)	1994-12-07
HU208147B (en)	1993-08-30
SE8802815D0 (sv)	1988-08-03
US5041424A (en)	1991-08-20
DK169344B1 (da)	1994-10-10
KR890003790A (ko)	1989-04-18
CZ541288A3 (cs)	1999-12-15
CN1061225A (zh)	1992-05-20
YU10390A (en)	1990-06-30
SE8802815L (sv)	1989-02-05
LU87290A1 (fr)	1990-02-07
NL970042I2 (fr)	2005-06-01
HU202547B (en)	1991-03-28
GB2207674A (en)	1989-02-08
NL8801934A (nl)	1989-03-01
SK541288A3 (en)	1998-10-07
CA1310637C (fr)	1992-11-24
GB8818462D0 (en)	1988-09-07
NO172440C (no)	1993-07-21
NO920277L (no)	1989-02-24
FI883596A0 (fi)	1988-08-01
FI87790C (fi)	1993-02-25
HU211960A9 (en)	1996-01-29
NL970042I1 (nl)	1998-03-02
MX9202851A (es)	1992-06-30
NO920665L (no)	1989-02-24
MX173843B (es)	1994-03-30
NO883299D0 (no)	1988-07-26
HU905862D0 (en)	1991-03-28
NO1998002I1 (no)	1998-01-14
DE3826562C2 (fr)	1993-04-08

Legal Events

Date	Code	Title	Description
2004-04-28	IF04	In force in the year 2004	Expiry date: 20080804

Publication	Publication Date	Title
DD299067A5 (de)	1992-03-26	Verfahren zur herstellung von zwischenprodukten fuer epipodophyllotoxinglucosid-4'-phosphat-derivate
DE69115694T2 (de)	1996-10-17	Phosphorylierte prodrugs
DE68906183T2 (de)	1993-09-02	2'-desoxy-5-fluoruridinderivate.
EP0098600A2 (fr)	1984-01-18	Dérivés de D-mannitol comme produits de départ pour la synthèse de phospholipides
EP0099068B1 (fr)	1987-09-30	Dérivés de glycérine pour la synthèse des phospholipides
EP0229128B1 (fr)	1990-05-30	Derives de glycero-3(2)-phospho-l-serine et preparations pharmaceutiques les contenant
DE60116081T2 (de)	2006-08-03	Bis-(n,n'-bis-(2-haloethyl)amino) phosphoramidate als antitumor-mittel
AT393505B (de)	1991-11-11	Arzneimittel, welche alkylphosphoamine in kombination mit einem alkylglycerin enthalten
EP0248858B1 (fr)	1990-02-28	Nouveaux composes phosphores et medicaments les contenant
DE19750508A1 (de)	1999-05-20	Neue Phospholipid-Addukte des 9-beta-D-Arabinofuranosyl-2-fluoradenins, ihre Herstellung und ihre pharmazeutische Verwendung
DE3606633A1 (de)	1987-09-03	Neue phosphoverbindungen und diese enthaltende arzneimittel
DE3631004A1 (de)	1988-03-24	Saccharid-phosphate und ihre ester und verfahren zu ihrer herstellung
DD252541A5 (de)	1987-12-23	Verfahren zur herstellung von phosphoverbindungen enthaltenden arzneimitteln fuer die tumorbehandlung
DE3641377A1 (de)	1987-09-03	Neue phosphorverbindungen und diese enthaltende arzneimittel
DD259405A5 (de)	1988-08-24	Verfahren zur herstellung von verbindungen mit cytotoxischer wirkung