NO303498B1 - AnalogifremgangsmÕte for fremstilling av terapeutisk aktive forbindelser - Google Patents

AnalogifremgangsmÕte for fremstilling av terapeutisk aktive forbindelser Download PDF

Info

Publication number: NO303498B1
Authority: NO; Norway
Prior art keywords: alkyl; compound; indole; tetrahydro; compounds
Prior art date: 1988-09-12

Application number

NO910958A

Other languages

English (en)

Norwegian (no)

Other versions

NO910958L (no

NO910958D0 (no

Inventor

Robert C Kelly

Paul A Aristoff

Original Assignee

Upjohn Co

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.)

1988-09-12

Filing date

1991-03-11

Publication date

1998-07-20

1991-03-11 Application filed by Upjohn Co filed Critical Upjohn Co

1991-03-11 Publication of NO910958D0 publication Critical patent/NO910958D0/no

1991-05-10 Publication of NO910958L publication Critical patent/NO910958L/no

1998-07-20 Publication of NO303498B1 publication Critical patent/NO303498B1/no

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 37
238000000034 method Methods 0.000 title claims description 13
238000002360 preparation method Methods 0.000 title claims description 7
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 20
-1 imino-1H-indole-5,2-di-carbonyl Chemical group 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
229940125904 compound 1 Drugs 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
150000002475 indoles Chemical class 0.000 claims description 6
229940125782 compound 2 Drugs 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 4
239000012445 acidic reagent Substances 0.000 claims description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 2
239000002246 antineoplastic agent Substances 0.000 abstract description 5
239000003242 anti bacterial agent Substances 0.000 abstract description 4
230000000259 anti-tumor effect Effects 0.000 abstract description 4
241001465754 Metazoa Species 0.000 abstract description 2
238000010171 animal model Methods 0.000 abstract description 2
239000006096 absorbing agent Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
239000000243 solution Substances 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
BYRVKDUQDLJUBX-JJCDCTGGSA-N adozelesin Chemical compound C1=CC=C2OC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)NC=C5C)=CC2=C1 BYRVKDUQDLJUBX-JJCDCTGGSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 8
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
206010028980 Neoplasm Diseases 0.000 description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
239000000539 dimer Substances 0.000 description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 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
239000002253 acid Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
ATFRLAFCRGJKAA-UHFFFAOYSA-N 5-[(2-carboxy-1h-indol-5-yl)carbamoylamino]-1h-indole-2-carboxylic acid Chemical compound C1=C2NC(C(O)=O)=CC2=CC(NC(=O)NC=2C=C3C=C(NC3=CC=2)C(=O)O)=C1 ATFRLAFCRGJKAA-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
UOWVMDUEMSNCAV-UHFFFAOYSA-N antibiotic cc 1065 Chemical compound N1C=2C(OC)=C(O)C=3N(C(N)=O)CCC=3C=2C=C1C(=O)N1CCC(C=2C=3)=C1C(O)=C(OC)C=2NC=3C(=O)N1CC2CC22C1=CC(=O)C1=C2C(C)=CN1 UOWVMDUEMSNCAV-UHFFFAOYSA-N 0.000 description 4
201000011510 cancer Diseases 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
208000032839 leukemia Diseases 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
241001529936 Murinae Species 0.000 description 3
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
239000003814 drug Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
USSLMJFJRWUITI-UHFFFAOYSA-N ethyl 5-[(2-ethoxycarbonyl-1h-indol-5-yl)carbamoylamino]-1h-indole-2-carboxylate Chemical compound C1=C2NC(C(=O)OCC)=CC2=CC(NC(=O)NC=2C=C3C=C(NC3=CC=2)C(=O)OCC)=C1 USSLMJFJRWUITI-UHFFFAOYSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
PUPKPAZSFZOLOR-UHFFFAOYSA-N n,n-dimethylformamide;toluene Chemical compound CN(C)C=O.CC1=CC=CC=C1 PUPKPAZSFZOLOR-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
230000004568 DNA-binding Effects 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
230000002906 microbiologic effect Effects 0.000 description 2
239000000203 mixture Substances 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
230000007306 turnover Effects 0.000 description 2
RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 description 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
125000005869 (methoxyethoxy)methanyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
MOQCFMZWVKQBAP-UHFFFAOYSA-N 1-[3,5-bis(trifluoromethyl)benzoyl]-n-(4-chlorophenyl)piperidine-3-carboxamide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C(=O)N2CC(CCC2)C(=O)NC=2C=CC(Cl)=CC=2)=C1 MOQCFMZWVKQBAP-UHFFFAOYSA-N 0.000 description 1
ULUNQYODBKLBOE-UHFFFAOYSA-N 2-(1h-pyrrol-2-yl)-1h-pyrrole Chemical compound C1=CNC(C=2NC=CC=2)=C1 ULUNQYODBKLBOE-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
208000001382 Experimental Melanoma Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
DSRXQXXHDIAVJT-UHFFFAOYSA-N acetonitrile;n,n-dimethylformamide Chemical compound CC#N.CN(C)C=O DSRXQXXHDIAVJT-UHFFFAOYSA-N 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
238000010306 acid treatment Methods 0.000 description 1
238000010564 aerobic fermentation Methods 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000004799 bromophenyl group Chemical group 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
239000012973 diazabicyclooctane Substances 0.000 description 1
238000007865 diluting Methods 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
WCGCOZXVVVIAEF-UHFFFAOYSA-N ethyl 5-amino-1h-indole-2-carboxylate Chemical compound NC1=CC=C2NC(C(=O)OCC)=CC2=C1 WCGCOZXVVVIAEF-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
WWECJGLXBSQKRF-UHFFFAOYSA-N n,n-dimethylformamide;methanol Chemical compound OC.CN(C)C=O WWECJGLXBSQKRF-UHFFFAOYSA-N 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000003786 synthesis reaction Methods 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
125000003944 tolyl group Chemical group 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
150000003673 urethanes Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Error Detection And Correction (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Artificial Filaments (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Amplifiers (AREA)
Solid State Image Pick-Up Elements (AREA)
Semiconductor Integrated Circuits (AREA)
Television Systems (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Peptides Or Proteins (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Stereophonic System (AREA)
Magnetic Resonance Imaging Apparatus (AREA)
Television Receiver Circuits (AREA)

NO910958A 1988-09-12 1991-03-11 AnalogifremgangsmÕte for fremstilling av terapeutisk aktive forbindelser NO303498B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US24335088A	1988-09-12	1988-09-12
PCT/US1989/003329 WO1990002746A1 (en)	1988-09-12	1989-08-07	Novel cc-1065 analogs having two cpi subunits

Publications (3)

Publication Number	Publication Date
NO910958D0 NO910958D0 (no)	1991-03-11
NO910958L NO910958L (no)	1991-05-10
NO303498B1 true NO303498B1 (no)	1998-07-20

Family

ID=22918400

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO910958A NO303498B1 (no)	1988-09-12	1991-03-11	AnalogifremgangsmÕte for fremstilling av terapeutisk aktive forbindelser

Country Status (14)

Country	Link
US (1)	US5541339A (cs)
JP (1)	JP3380237B2 (cs)
KR (1)	KR0137959B1 (cs)
AT (1)	ATE198335T1 (cs)
AU (1)	AU632288B2 (cs)
CA (1)	CA1340215C (cs)
DE (1)	DE68929275T2 (cs)
DK (1)	DK175458B1 (cs)
FI (1)	FI103668B1 (cs)
GR (1)	GR3035589T3 (cs)
LV (1)	LV12806B (cs)
NO (1)	NO303498B1 (cs)
TW (1)	TW217383B (cs)
WO (1)	WO1990002746A1 (cs)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2076465C (en) *	1992-03-25	2002-11-26	Ravi V. J. Chari	Cell binding agent conjugates of analogues and derivatives of cc-1065
US5502068A (en) *	1995-01-31	1996-03-26	Synphar Laboratories, Inc.	Cyclopropylpyrroloindole-oligopeptide anticancer agents
US20100056762A1 (en)	2001-05-11	2010-03-04	Old Lloyd J	Specific binding proteins and uses thereof
US7589180B2 (en)	2001-05-11	2009-09-15	Abbott Laboratories Inc.	Specific binding proteins and uses thereof
BR0214019A (pt)	2001-11-09	2004-10-13	Boehringer Ingelheim Phamaceut	Benzimidazóis úteis como inibidores de proteìna quinase
EP1529046A1 (en) *	2002-08-08	2005-05-11	Boehringer Ingelheim Pharmaceuticals Inc.	Substituted benzimidazole compounds
JP2006505571A (ja) *	2002-10-15	2006-02-16	リゲルファーマシューテイカルズ、インコーポレイテッド	置換されたインドール及びｈｃｖ阻害剤としてのその使用
US20070213374A1 (en) *	2003-07-07	2007-09-13	Merck Patent Gmbh	Malonamide Derivatives
WO2005079791A1 (en) *	2004-02-12	2005-09-01	Boehringer Ingelheim Pharmaceuticals, Inc.	Thiophene -2- carboxylic acid - (1h - benzimidazol - 2 yl) - amide derivatives and related compounds as inhibitors of the tec kinase itk (interleukin -2- inducible t cell kinase) for the treatment of inflammation, immunological and allergic disorders
US7446195B2 (en) *	2005-08-17	2008-11-04	Schering Corporation	High affinity thiophene-based and furan-based kinase ligands
EP2126127B1 (en)	2007-01-25	2016-09-28	Dana-Farber Cancer Institute, Inc.	Use of anti-egfr antibodies in treatment of egfr mutant mediated disease
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US9901567B2 (en)	2007-08-01	2018-02-27	Syntarga B.V.	Substituted CC-1065 analogs and their conjugates
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1989
- 1989-08-07 JP JP50923689A patent/JP3380237B2/ja not_active Expired - Fee Related
- 1989-08-07 WO PCT/US1989/003329 patent/WO1990002746A1/en not_active Ceased
- 1989-08-07 AU AU41922/89A patent/AU632288B2/en not_active Ceased
- 1989-08-07 US US07/659,415 patent/US5541339A/en not_active Expired - Fee Related
- 1989-08-07 KR KR1019900700977A patent/KR0137959B1/ko not_active Expired - Fee Related
- 1989-08-21 CA CA000608908A patent/CA1340215C/en not_active Expired - Fee Related
- 1989-08-23 TW TW078106510A patent/TW217383B/zh active
- 1989-09-04 DE DE68929275T patent/DE68929275T2/de not_active Expired - Fee Related
- 1989-09-04 AT AT89308920T patent/ATE198335T1/de not_active IP Right Cessation
1991
- 1991-03-08 DK DK41791A patent/DK175458B1/da not_active IP Right Cessation
- 1991-03-11 NO NO910958A patent/NO303498B1/no unknown
- 1991-03-11 FI FI911193A patent/FI103668B1/fi not_active IP Right Cessation
2001
- 2001-03-15 GR GR20010400433T patent/GR3035589T3/el not_active IP Right Cessation
- 2001-12-27 LV LV010180A patent/LV12806B/xx unknown

Also Published As

Publication number	Publication date
JP3380237B2 (ja)	2003-02-24
LV12806B (lv)	2002-05-20
CA1340215C (en)	1998-12-15
DK41791A (da)	1991-03-08
WO1990002746A1 (en)	1990-03-22
DE68929275D1 (de)	2001-02-01
DK41791D0 (da)	1991-03-08
KR900701801A (ko)	1990-12-04
ATE198335T1 (de)	2001-01-15
TW217383B (cs)	1993-12-11
NO910958L (no)	1991-05-10
KR0137959B1 (ko)	1998-05-15
DK175458B1 (da)	2004-11-01
DE68929275T2 (de)	2001-05-23
FI103668B (fi)	1999-08-13
AU4192289A (en)	1990-04-02
JPH04500664A (ja)	1992-02-06
GR3035589T3 (en)	2001-06-29
LV12806A (en)	2002-03-20
US5541339A (en)	1996-07-30
NO910958D0 (no)	1991-03-11
AU632288B2 (en)	1992-12-24
FI103668B1 (fi)	1999-08-13
FI911193A0 (fi)	1991-03-11

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