OA11551A - Combinations of protein farnesyltransferase and HMG COA reductase inhibitors and their use to treat cancer. - Google Patents

Combinations of protein farnesyltransferase and HMG COA reductase inhibitors and their use to treat cancer. Download PDF

Info

Publication number: OA11551A
Authority: OA; OAPI
Prior art keywords: methyl; phenyl; benzyl; carbamoyl; ethyl
Prior art date: 1998-05-12

Application number

OA1200000310A

Other languages

English (en)

Inventor

Judith Leopold

Roger Schofield Newton

Original Assignee

Warner Lambert 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.)

1998-05-12

Filing date

1999-05-10

Publication date

2004-05-24

1999-05-10 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2004-05-24 Publication of OA11551A publication Critical patent/OA11551A/en

Links

206010028980 Neoplasm Diseases 0.000 title claims abstract description 35
201000011510 cancer Diseases 0.000 title claims abstract description 29
229940121710 HMGCoA reductase inhibitor Drugs 0.000 title claims description 17
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title claims description 17
108010054353 p21(ras) farnesyl-protein transferase Proteins 0.000 title abstract description 34
239000003528 protein farnesyltransferase inhibitor Substances 0.000 title description 11
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title description 7
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims abstract description 19
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims abstract description 19
208000037803 restenosis Diseases 0.000 claims abstract description 14
201000004681 Psoriasis Diseases 0.000 claims abstract description 7
208000036142 Viral infection Diseases 0.000 claims abstract description 6
230000009385 viral infection Effects 0.000 claims abstract description 6
-1 -N3 Chemical group 0.000 claims description 111
150000001875 compounds Chemical class 0.000 claims description 105
125000000217 alkyl group Chemical group 0.000 claims description 91
229910052739 hydrogen Inorganic materials 0.000 claims description 71
239000001257 hydrogen Substances 0.000 claims description 71
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
150000002431 hydrogen Chemical class 0.000 claims description 34
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
150000002148 esters Chemical class 0.000 claims description 30
150000001408 amides Chemical class 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 24
239000000651 prodrug Substances 0.000 claims description 23
229940002612 prodrug Drugs 0.000 claims description 23
229910052736 halogen Inorganic materials 0.000 claims description 21
150000002367 halogens Chemical class 0.000 claims description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
239000000203 mixture Substances 0.000 claims description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
230000002401 inhibitory effect Effects 0.000 claims description 17
229910017711 NHRa Inorganic materials 0.000 claims description 15
PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 13
229960004844 lovastatin Drugs 0.000 claims description 13
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical group C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 13
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 13
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
229940080818 propionamide Drugs 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims description 6
230000000694 effects Effects 0.000 claims description 6
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 6
238000011282 treatment Methods 0.000 claims description 6
101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
206010005003 Bladder cancer Diseases 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 4
125000001072 heteroaryl group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
BMXRIUNRNBDEIQ-RDFKHQOOSA-N (2s)-2-(benzylcarbamoylamino)-3-(1h-imidazol-5-yl)-n-[2-oxo-2-(2-phenylpropylamino)ethyl]-n-[(4-phenylmethoxyphenyl)methyl]propanamide Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)NCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 BMXRIUNRNBDEIQ-RDFKHQOOSA-N 0.000 claims description 3
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GKJYLSQGRPYXPA-LJAQVGFWSA-N (2s)-2-(benzylcarbamoylamino)-n-[(4-chlorophenyl)methyl]-3-(1h-imidazol-5-yl)-n-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]propanamide Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)NCC=1C=CC=CC=1)CC1=CC=C(Cl)C=C1 GKJYLSQGRPYXPA-LJAQVGFWSA-N 0.000 claims description 2
FYZLYRZHHZRXRN-HKBQPEDESA-N (2s)-2-acetamido-3-(1h-imidazol-5-yl)-n-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-n-[(4-phenylmethoxyphenyl)methyl]propanamide Chemical compound C([C@H](NC(=O)C)C(=O)N(CC(=O)NCC(C)(C)C=1C=CC=CC=1)CC=1C=CC(OCC=2C=CC=CC=2)=CC=1)C1=CN=CN1 FYZLYRZHHZRXRN-HKBQPEDESA-N 0.000 claims description 2
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 claims description 2
206010006187 Breast cancer Diseases 0.000 claims description 2
208000026310 Breast neoplasm Diseases 0.000 claims description 2
101150047265 COR2 gene Proteins 0.000 claims description 2
101150084419 CSR2 gene Proteins 0.000 claims description 2
101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 2
229910003204 NH2 Inorganic materials 0.000 claims description 2
101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 claims description 2
208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
ILMZVWUPVVZVEF-FZNWDQQTSA-N benzyl n-[(2s)-1-[(4-chlorophenyl)methyl-[1-[(2-methyl-2-phenylpropyl)amino]-1-oxopropan-2-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)C(C)N(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(Cl)C=C1 ILMZVWUPVVZVEF-FZNWDQQTSA-N 0.000 claims description 2
NPVIMMQTVLPHKV-RWYGWLOXSA-N benzyl n-[(2s)-1-[[2-(2,2-diphenylethylamino)-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 NPVIMMQTVLPHKV-RWYGWLOXSA-N 0.000 claims description 2
JBQKDWCCSNPPMR-SFCXHYMASA-N benzyl n-[(2s)-1-[[2-[(2-hydroxy-2-phenylethyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(O)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 JBQKDWCCSNPPMR-SFCXHYMASA-N 0.000 claims description 2
BNSYCEGVHLCVSI-NPJBGSGMSA-N benzyl n-[(2s)-1-[[2-[2-(2-chlorophenyl)propylamino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=C(Cl)C=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 BNSYCEGVHLCVSI-NPJBGSGMSA-N 0.000 claims description 2
XTIYEBMDXGBHOO-HKBQPEDESA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-methoxyphenyl)methyl-[2-oxo-2-[(1-phenylcyclobutyl)methylamino]ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC1(C=2C=CC=CC=2)CCC1 XTIYEBMDXGBHOO-HKBQPEDESA-N 0.000 claims description 2
ABXXMASKQPMUOQ-QNGSWNHHSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-methylphenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(C)C=C1 ABXXMASKQPMUOQ-QNGSWNHHSA-N 0.000 claims description 2
XSNSVLNJHGTYTL-NDEPHWFRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-(pyridin-4-ylmethyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=NC=C1 XSNSVLNJHGTYTL-NDEPHWFRSA-N 0.000 claims description 2
HNXRTWHXWCHGID-QNGWXLTQSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[(1-phenylcyclobutyl)methylamino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate Chemical compound C1CCC1(C=1C=CC=CC=1)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 HNXRTWHXWCHGID-QNGWXLTQSA-N 0.000 claims description 2
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 2
201000005202 lung cancer Diseases 0.000 claims description 2
208000020816 lung neoplasm Diseases 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
201000002510 thyroid cancer Diseases 0.000 claims description 2
201000005112 urinary bladder cancer Diseases 0.000 claims description 2
NPQAANZPYSZXMQ-QNGWXLTQSA-N (2s)-2-(benzylcarbamoylamino)-3-(1h-imidazol-5-yl)-n-[2-oxo-2-[(1-phenylcyclobutyl)methylamino]ethyl]-n-[(4-phenylmethoxyphenyl)methyl]propanamide Chemical compound C1CCC1(C=1C=CC=CC=1)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)NCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 NPQAANZPYSZXMQ-QNGWXLTQSA-N 0.000 claims 1
GZDQXBPGVLDSMB-QNGWXLTQSA-N (4-methoxyphenyl)methyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)N[C@H](C(=O)N(CC(=O)NCC(C)(C)C=1C=CC=CC=1)CC=1C=CC(OCC=2C=CC=CC=2)=CC=1)CC1=CN=CN1 GZDQXBPGVLDSMB-QNGWXLTQSA-N 0.000 claims 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
101100379079 Emericella variicolor andA gene Proteins 0.000 claims 1
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LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 claims 1
RDXDECXODBTMOR-IZCXSWDTSA-N benzyl n-[(2s)-1-[(2-chlorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1Cl RDXDECXODBTMOR-IZCXSWDTSA-N 0.000 claims 1
SSXFUPUONWGRIP-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-chlorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(Cl)C=C1 SSXFUPUONWGRIP-IZCXSWDTSA-N 0.000 claims 1
QCNOUBMNVDBZBN-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-fluorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(F)C=C1 QCNOUBMNVDBZBN-IZCXSWDTSA-N 0.000 claims 1
SMBHALUVUUYXQI-CRGCAJGSSA-N benzyl n-[(2s)-1-[[2-[(2-cyano-2-phenylethyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C#N)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 SMBHALUVUUYXQI-CRGCAJGSSA-N 0.000 claims 1
YDVQFZBNLASSIP-PQEJLDEPSA-N benzyl n-[(2s)-1-[[2-[[2-(2-chlorophenyl)-2-phenylethyl]amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound ClC1=CC=CC=C1C(C=1C=CC=CC=1)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 YDVQFZBNLASSIP-PQEJLDEPSA-N 0.000 claims 1
NNRXKWAHWANQLM-QNGSWNHHSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(3-methylphenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC(C)=C1 NNRXKWAHWANQLM-QNGSWNHHSA-N 0.000 claims 1
NWSAOVCSJUGBPY-PMERELPUSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-methylphenyl)methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 NWSAOVCSJUGBPY-PMERELPUSA-N 0.000 claims 1
UKDHPFDMEXGIKI-HKBQPEDESA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[2-(4-methoxyphenyl)ethyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CCN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 UKDHPFDMEXGIKI-HKBQPEDESA-N 0.000 claims 1
ZZRLVJNHLQRVBB-DHUJRADRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[[4-(pyridin-2-ylmethoxy)phenyl]methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=N1 ZZRLVJNHLQRVBB-DHUJRADRSA-N 0.000 claims 1
MDHGWUKTVUNWAA-DHUJRADRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[[4-(pyridin-4-ylmethoxy)phenyl]methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=NC=C1 MDHGWUKTVUNWAA-DHUJRADRSA-N 0.000 claims 1
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230000002035 prolonged effect Effects 0.000 description 1
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238000000746 purification Methods 0.000 description 1
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108091006091 regulatory enzymes Proteins 0.000 description 1
201000010174 renal carcinoma Diseases 0.000 description 1
230000004044 response Effects 0.000 description 1
CXKKQMGFHKGJFE-QNGWXLTQSA-N s-benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[(1-phenylcyclobutyl)methylamino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamothioate Chemical compound C1CCC1(C=1C=CC=CC=1)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)SCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 CXKKQMGFHKGJFE-QNGWXLTQSA-N 0.000 description 1
210000003752 saphenous vein Anatomy 0.000 description 1
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239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000002356 single layer Substances 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
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239000007921 spray Substances 0.000 description 1
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239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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230000002195 synergetic effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
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239000000454 talc Substances 0.000 description 1
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125000002298 terpene group Chemical group 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
210000001550 testis Anatomy 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
XGTRBPFMSCBERG-UMSFTDKQSA-N thiophen-3-ylmethyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC1=CSC=C1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 XGTRBPFMSCBERG-UMSFTDKQSA-N 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000002463 transducing effect Effects 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
230000004222 uncontrolled growth Effects 0.000 description 1
208000010576 undifferentiated carcinoma Diseases 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
- 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

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Dermatology (AREA)
Virology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Peptides Or Proteins (AREA)

OA1200000310A 1998-05-12 1999-05-10 Combinations of protein farnesyltransferase and HMG COA reductase inhibitors and their use to treat cancer. OA11551A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US8520298P	1998-05-12	1998-05-12
US9225398P	1998-07-10	1998-07-10

Publications (1)

Publication Number	Publication Date
OA11551A true OA11551A (en)	2004-05-24

Family

ID=26772425

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200000310A OA11551A (en)	1998-05-12	1999-05-10	Combinations of protein farnesyltransferase and HMG COA reductase inhibitors and their use to treat cancer.

Country Status (25)

Country	Link
US (1)	US6492410B1 (is)
EP (1)	EP1077949A2 (is)
JP (1)	JP2002514628A (is)
KR (1)	KR20010043529A (is)
CN (1)	CN1171874C (is)
AP (1)	AP2000001984A0 (is)
AU (1)	AU758891B2 (is)
BG (1)	BG105003A (is)
BR (1)	BR9911785A (is)
CA (1)	CA2331295A1 (is)
EA (1)	EA003860B1 (is)
EE (1)	EE200000660A (is)
GE (1)	GEP20032996B (is)
HR (1)	HRP20000771A2 (is)
HU (1)	HUP0102322A3 (is)
ID (1)	ID27933A (is)
IL (1)	IL139502A0 (is)
IS (1)	IS5713A (is)
NO (1)	NO20005680L (is)
NZ (1)	NZ508357A (is)
OA (1)	OA11551A (is)
PL (1)	PL344662A1 (is)
SK (1)	SK16742000A3 (is)
WO (1)	WO1999058505A2 (is)
YU (1)	YU68900A (is)

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JP2002536405A (ja) *	1999-02-11	2002-10-29	イーデンランド、インコーポレイテッド	ウイルス感染症の治療方法
US6455734B1 (en) *	2000-08-09	2002-09-24	Magnesium Diagnostics, Inc.	Antagonists of the magnesium binding defect as therapeutic agents and methods for treatment of abnormal physiological states
US20020010128A1 (en) *	2000-04-13	2002-01-24	Parks Thomas P.	Treatment of hyperproliferative, inflammatory and related mucocutaneous disorders using inhibitors of mevalonate synthesis and metabolism
US20020132781A1 (en) *	2000-10-06	2002-09-19	George Kindness	Combination and method of treatment of cancer utilizing a COX-2 inhibitor and A 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor
GB0220885D0 (en) *	2002-09-09	2002-10-16	Novartis Ag	Organic compounds
WO2005042710A1 (en) *	2003-10-28	2005-05-12	The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services	Use of statin to kill ebv-transformed b cells
WO2007054896A1 (en) *	2005-11-08	2007-05-18	Ranbaxy Laboratories Limited	Process for (3r, 5r)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4- [(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3, 5-dihydroxy-heptanoic acid hemi calcium salt
KR100930365B1 (ko) *	2006-11-09	2009-12-08	덕성여자대학교 산학협력단	심바스타틴을 유효성분으로 함유하는 유방암 치료용 약학적조성물
US20080119444A1 (en) *	2006-11-16	2008-05-22	Steven Lehrer	Methods and compositions for the treatment of cancer
US11344497B1 (en)	2017-12-08	2022-05-31	Quicksilver Scientific, Inc.	Mitochondrial performance enhancement nanoemulsion
US10722465B1 (en)	2017-12-08	2020-07-28	Quicksilber Scientific, Inc.	Transparent colloidal vitamin supplement
US11291702B1 (en)	2019-04-15	2022-04-05	Quicksilver Scientific, Inc.	Liver activation nanoemulsion, solid binding composition, and toxin excretion enhancement method

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK523288A (da) *	1987-10-06	1989-04-07	Hoffmann La Roche	Aminosyrederivater
NL9002031A (nl)	1990-09-14	1992-04-01	Voskuilen Woudenberg Bv	Inrichting voor het bewerken van een uitwendig buisoppervlak.
US5571792A (en) *	1994-06-30	1996-11-05	Warner-Lambert Company	Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase
ES2202455T3 (es)	1995-06-22	2004-04-01	Biogen, Inc.	Cristales de fragmentos del ligando cd40 y su uso.
EP0833845A1 (en) *	1995-06-22	1998-04-08	Novo Nordisk A/S	Compounds with growth hormone releasing properties
UA57081C2 (uk) *	1997-06-16	2003-06-16	Пфайзер Продактс Інк.	Фармацевтична композиція для лікування раку або доброякісних проліферативних хвороб у ссавців, спосіб лікування, фармацевтична композиція для інгібування ненормального росту клітин у ссавців та спосіб інгібування

1999
- 1999-05-10 YU YU68900A patent/YU68900A/sh unknown
- 1999-05-10 OA OA1200000310A patent/OA11551A/en unknown
- 1999-05-10 CN CNB99807649XA patent/CN1171874C/zh not_active Expired - Fee Related
- 1999-05-10 US US09/674,818 patent/US6492410B1/en not_active Expired - Fee Related
- 1999-05-10 HR HR20000771A patent/HRP20000771A2/hr not_active Application Discontinuation
- 1999-05-10 EP EP99922898A patent/EP1077949A2/en not_active Withdrawn
- 1999-05-10 SK SK1674-2000A patent/SK16742000A3/sk unknown
- 1999-05-10 CA CA002331295A patent/CA2331295A1/en not_active Abandoned
- 1999-05-10 AU AU39792/99A patent/AU758891B2/en not_active Ceased
- 1999-05-10 AP APAP/P/2000/001984A patent/AP2000001984A0/en unknown
- 1999-05-10 JP JP2000548309A patent/JP2002514628A/ja active Pending
- 1999-05-10 HU HU0102322A patent/HUP0102322A3/hu unknown
- 1999-05-10 EA EA200001164A patent/EA003860B1/ru not_active IP Right Cessation
- 1999-05-10 ID IDW20002583A patent/ID27933A/id unknown
- 1999-05-10 WO PCT/US1999/010188 patent/WO1999058505A2/en not_active Ceased
- 1999-05-10 IL IL13950299A patent/IL139502A0/xx unknown
- 1999-05-10 BR BR9911785-1A patent/BR9911785A/pt not_active IP Right Cessation
- 1999-05-10 KR KR1020007012632A patent/KR20010043529A/ko not_active Ceased
- 1999-05-10 EE EEP200000660A patent/EE200000660A/xx unknown
- 1999-05-10 PL PL99344662A patent/PL344662A1/xx not_active Application Discontinuation
- 1999-05-10 NZ NZ508357A patent/NZ508357A/xx unknown
- 1999-05-10 GE GEAP19995670A patent/GEP20032996B/en unknown
2000
- 2000-11-10 NO NO20005680A patent/NO20005680L/no not_active Application Discontinuation
- 2000-11-10 IS IS5713A patent/IS5713A/is unknown
- 2000-11-29 BG BG105003A patent/BG105003A/xx unknown

Also Published As

Publication number	Publication date
ID27933A (id)	2001-05-03
AU3979299A (en)	1999-11-29
HUP0102322A3 (en)	2001-12-28
EE200000660A (et)	2002-04-15
US6492410B1 (en)	2002-12-10
CN1171874C (zh)	2004-10-20
WO1999058505A2 (en)	1999-11-18
IL139502A0 (en)	2001-11-25
GEP20032996B (en)	2003-06-25
HUP0102322A2 (hu)	2001-11-28
YU68900A (sh)	2002-12-10
EA003860B1 (ru)	2003-10-30
CN1306515A (zh)	2001-08-01
EA200001164A1 (ru)	2001-06-25
CA2331295A1 (en)	1999-11-18
NZ508357A (en)	2002-09-27
PL344662A1 (en)	2001-11-19
WO1999058505A3 (en)	2000-01-06
AP2000001984A0 (en)	2000-12-31
BR9911785A (pt)	2001-04-03
HK1038355A1 (en)	2002-03-15
BG105003A (en)	2001-07-31
HRP20000771A2 (en)	2001-06-30
SK16742000A3 (sk)	2001-07-10
NO20005680D0 (no)	2000-11-10
NO20005680L (no)	2001-01-10
EP1077949A2 (en)	2001-02-28
AU758891B2 (en)	2003-04-03
JP2002514628A (ja)	2002-05-21
KR20010043529A (ko)	2001-05-25
IS5713A (is)	2000-11-10

Publication	Publication Date	Title
US6300501B1 (en)	2001-10-09	Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase
US6369034B1 (en)	2002-04-09	Functionalized alkyl and alenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors
BG102936A (bg)	1999-09-30	Инхибитори на протеин фарнезил трансфераза
OA11551A (en)	2004-05-24	Combinations of protein farnesyltransferase and HMG COA reductase inhibitors and their use to treat cancer.
US6265382B1 (en)	2001-07-24	Dipeptide inhibitors of protein farnesyltransferase
EP0951471B1 (en)	2004-03-17	Cycloalkyl inhibitors of protein farnesyltransferase
US6737410B1 (en)	2004-05-18	Inhibitors of protein farnesyl transferase
ZA200006491B (en)	2002-05-09	Combinations of protein farnesyltransferase and HMG CoA reductase inhibitors and their use to treat cancer.
MXPA00011113A (en)	2001-07-31	Combinations of protein farnesyltransferase and hmg coa reductase inhibitors and their use to treat cancer
CZ20004073A3 (cs)	2001-03-14	Kombinace proteinové farnesyl transferázy a inhibitorů HMG CoA reduktázy a jejich použití při léčbě rakoviny
MXPA99001592A (es)	1999-09-20	Inhibidores cicloalquilo de proteina farnesiltransferasa
MXPA00009613A (en)	2001-07-31	Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors
KR20000015892A (ko)	2000-03-15	단백질 파르네실 트랜스퍼라제의 억제제
HUP9903221A2 (hu)	2000-02-28	A protein farneliz transzferáz enzimet gátló vegyületek