SK286568B6 - Inhibítory farnezyl proteín transferázy - Google Patents

Inhibítory farnezyl proteín transferázy Download PDF

Info

Publication number: SK286568B6
Authority: SK; Slovakia
Prior art keywords: compound; room temperature; benzodiazepine; tetrahydro; solution
Prior art date: 1996-02-26

Application number

SK1173-98A

Other languages

English (en)

Slovak (sk)

Other versions

SK117398A3 (en

Inventor

Charles Z. Ding

T. Hunt John

Soong-Hoon Kim

Toomas Mitt

Raheev Bhide

Katerina Leftheris

Original Assignee

Bristol-Myers Squibb Company

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.)

1996-02-26

Filing date

1997-02-24

Publication date

2009-01-07

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26683350&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK286568(B6) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1997-02-24 Application filed by Bristol-Myers Squibb Company filed Critical Bristol-Myers Squibb Company

2000-12-11 Publication of SK117398A3 publication Critical patent/SK117398A3/sk

2009-01-07 Publication of SK286568B6 publication Critical patent/SK286568B6/sk

Links

102000004357 Transferases Human genes 0.000 title claims abstract description 14
108090000992 Transferases Proteins 0.000 title claims abstract description 14
125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 title abstract description 5
239000003112 inhibitor Substances 0.000 title description 3
206010028980 Neoplasm Diseases 0.000 claims abstract description 16
201000010099 disease Diseases 0.000 claims abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
108090000623 proteins and genes Proteins 0.000 claims abstract description 9
102000004169 proteins and genes Human genes 0.000 claims abstract description 8
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
102000004190 Enzymes Human genes 0.000 claims abstract description 4
108090000790 Enzymes Proteins 0.000 claims abstract description 4
102000019337 Prenyltransferases Human genes 0.000 claims abstract description 3
108050006837 Prenyltransferases Proteins 0.000 claims abstract description 3
125000002686 geranylgeranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 3
230000019491 signal transduction Effects 0.000 claims abstract description 3
230000002401 inhibitory effect Effects 0.000 claims abstract 4
150000001875 compounds Chemical class 0.000 claims description 133
150000003839 salts Chemical class 0.000 claims description 14
102000016914 ras Proteins Human genes 0.000 abstract description 9
108010014186 ras Proteins Proteins 0.000 abstract description 4
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 abstract description 2
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 222
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
239000000243 solution Substances 0.000 description 120
-1 aliphatic amino acid Chemical class 0.000 description 96
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 79
239000000203 mixture Substances 0.000 description 78
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 69
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
239000007787 solid Substances 0.000 description 56
238000006243 chemical reaction Methods 0.000 description 55
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
239000000047 product Substances 0.000 description 44
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
235000019439 ethyl acetate Nutrition 0.000 description 41
239000003960 organic solvent Substances 0.000 description 37
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 35
229940126062 Compound A Drugs 0.000 description 32
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 32
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 32
239000002904 solvent Substances 0.000 description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 31
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 30
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 28
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
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KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
239000002253 acid Substances 0.000 description 23
239000012321 sodium triacetoxyborohydride Substances 0.000 description 23
229940126214 compound 3 Drugs 0.000 description 22
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
229940049706 benzodiazepine Drugs 0.000 description 21
238000011282 treatment Methods 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 20
229940125782 compound 2 Drugs 0.000 description 20
239000012442 inert solvent Substances 0.000 description 20
230000002829 reductive effect Effects 0.000 description 20
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
229910052938 sodium sulfate Inorganic materials 0.000 description 18
235000011152 sodium sulphate Nutrition 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
239000002585 base Substances 0.000 description 16
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 16
ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 15
229910052786 argon Inorganic materials 0.000 description 14
229940125898 compound 5 Drugs 0.000 description 14
239000012044 organic layer Substances 0.000 description 14
238000010992 reflux Methods 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
235000017557 sodium bicarbonate Nutrition 0.000 description 14
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
239000000908 ammonium hydroxide Substances 0.000 description 13
229960001701 chloroform Drugs 0.000 description 13
239000000284 extract Substances 0.000 description 13
229910052736 halogen Inorganic materials 0.000 description 13
150000002367 halogens Chemical class 0.000 description 13
239000012267 brine Substances 0.000 description 12
229910052794 bromium Inorganic materials 0.000 description 12
238000003818 flash chromatography Methods 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
239000000725 suspension Substances 0.000 description 12
150000001299 aldehydes Chemical class 0.000 description 11
239000010410 layer Substances 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
150000001412 amines Chemical class 0.000 description 10
235000001014 amino acid Nutrition 0.000 description 10
229910000085 borane Inorganic materials 0.000 description 10
238000000034 method Methods 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
229910052739 hydrogen Inorganic materials 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
238000005932 reductive alkylation reaction Methods 0.000 description 9
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
229940125904 compound 1 Drugs 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
238000002953 preparative HPLC Methods 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 7
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 7
239000003638 chemical reducing agent Substances 0.000 description 7
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239000012280 lithium aluminium hydride Substances 0.000 description 7
238000004458 analytical method Methods 0.000 description 6
150000001732 carboxylic acid derivatives Chemical group 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
150000004678 hydrides Chemical class 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
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WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
206010025323 Lymphomas Diseases 0.000 description 5
150000001413 amino acids Chemical class 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical group [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 5
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
230000009467 reduction Effects 0.000 description 5
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BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
238000003756 stirring Methods 0.000 description 5
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 5
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 5
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 4
0 *c1cc(CN([C@](Cc2ccccc2)CC2CCCC3=CN=IN3)S(c3cccc(Br)c3)(=*)=O)c2cc1 Chemical compound *c1cc(CN([C@](Cc2ccccc2)CC2CCCC3=CN=IN3)S(c3cccc(Br)c3)(=*)=O)c2cc1 0.000 description 4
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238000005481 NMR spectroscopy Methods 0.000 description 4
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230000010933 acylation Effects 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
238000009835 boiling Methods 0.000 description 4
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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239000002808 molecular sieve Substances 0.000 description 4
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
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239000001119 stannous chloride Substances 0.000 description 4
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JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
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238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
OMWIVVBFLHFASJ-UHFFFAOYSA-N 1h-1,2-benzodiazepin-1-ium;chloride Chemical compound Cl.N1N=CC=CC2=CC=CC=C12 OMWIVVBFLHFASJ-UHFFFAOYSA-N 0.000 description 3
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
- 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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

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SK1173-98A 1996-02-26 1997-02-24 Inhibítory farnezyl proteín transferázy SK286568B6 (sk)

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Application Number	Priority Date	Filing Date	Title
US1226596P	1996-02-26	1996-02-26
US2280596P	1996-07-25	1996-07-25
PCT/US1997/002920 WO1997030992A1 (en)	1996-02-26	1997-02-24	Inhibitors of farnesyl protein transferase

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SK117398A3 SK117398A3 (en)	2000-12-11
SK286568B6 true SK286568B6 (sk)	2009-01-07

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SK1173-98A SK286568B6 (sk)	1996-02-26	1997-02-24	Inhibítory farnezyl proteín transferázy

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EP (2)	EP0892797A4 (cs)
JP (1)	JP4115529B2 (cs)
KR (1)	KR100522983B1 (cs)
CN (2)	CN100376569C (cs)
AU (1)	AU718676B2 (cs)
BG (1)	BG64951B1 (cs)
BR (1)	BR9707614A (cs)
CA (1)	CA2239187C (cs)
CZ (1)	CZ299762B6 (cs)
EE (1)	EE04309B1 (cs)
GE (1)	GEP20022616B (cs)
HU (1)	HUP9902016A3 (cs)
IL (2)	IL124197A (cs)
LV (1)	LV12150B (cs)
NO (1)	NO319395B1 (cs)
NZ (1)	NZ330287A (cs)
PL (1)	PL191502B1 (cs)
RO (1)	RO121118B1 (cs)
RU (1)	RU2225405C2 (cs)
SK (1)	SK286568B6 (cs)
TW (1)	TW496863B (cs)
UA (1)	UA52642C2 (cs)
WO (1)	WO1997030992A1 (cs)

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BR9707614A (pt)	1999-07-27
HUP9902016A3 (en)	2000-02-28
KR100522983B1 (ko)	2006-09-20
CA2239187C (en)	2003-04-22
LV12150A (lv)	1998-10-20
JP2000502356A (ja)	2000-02-29
CZ299762B6 (cs)	2008-11-12
CN100376569C (zh)	2008-03-26
EE04309B1 (et)	2004-06-15
BG64951B1 (bg)	2006-10-31
IL124197A (en)	2003-06-24
IL141908A0 (en)	2002-03-10
GEP20022616B (en)	2002-01-25
US6455523B1 (en)	2002-09-24
NO983892L (no)	1998-08-25
CZ269698A3 (cs)	1999-10-13
PL191502B1 (pl)	2006-05-31
WO1997030992A1 (en)	1997-08-28
SK117398A3 (en)	2000-12-11
NO983892D0 (no)	1998-08-25
CA2239187A1 (en)	1997-08-28
EE9800262A (et)	1999-02-15
AU718676B2 (en)	2000-04-20
CN1347881A (zh)	2002-05-08
UA52642C2 (uk)	2003-01-15
TW496863B (en)	2002-08-01
IL141908A (en)	2003-04-10
EP1481975A1 (en)	2004-12-01
EP0892797A1 (en)	1999-01-27
RO121118B1 (ro)	2006-12-29
CN1214685A (zh)	1999-04-21
LV12150B (en)	1998-12-20
NZ330287A (en)	2000-03-27
RU2225405C2 (ru)	2004-03-10
HUP9902016A2 (hu)	1999-09-28
PL328868A1 (en)	1999-03-01
BG102738A (en)	1999-09-30
US6011029A (en)	2000-01-04
EP0892797A4 (en)	2004-10-20
JP4115529B2 (ja)	2008-07-09
KR19990087250A (ko)	1999-12-15
AU2136697A (en)	1997-09-10
NO319395B1 (no)	2005-08-08

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