ZA200006035B - Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors. - Google Patents

Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors. Download PDF

Info

Publication number: ZA200006035B
Authority: ZA; South Africa
Prior art keywords: methyl; compound; phenyl; amino; composition
Prior art date: 1998-04-27

Application number

ZA200006035A

Other languages

English (en)

Inventor

Annette Marian Doherty

James Stanley Katlenbronn

Daniele Marie Leonard

Dennis Joseph Mcnamara

John Quin Iii

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.)

1998-04-27

Filing date

2000-10-26

Publication date

2002-01-28

2000-10-26 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2002-01-28 Publication of ZA200006035B publication Critical patent/ZA200006035B/en

Links

125000000217 alkyl group Chemical group 0.000 title claims description 17
125000003342 alkenyl group Chemical group 0.000 title claims description 6
239000003528 protein farnesyltransferase inhibitor Substances 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 42
238000000034 method Methods 0.000 claims abstract description 33
206010028980 Neoplasm Diseases 0.000 claims abstract description 30
208000037803 restenosis Diseases 0.000 claims abstract description 25
201000011510 cancer Diseases 0.000 claims abstract description 24
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 14
239000000203 mixture Substances 0.000 claims abstract 13
-1 2-methyl-2- phenylpropyl Chemical group 0.000 claims description 25
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
150000001408 amides Chemical class 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
239000000651 prodrug Substances 0.000 claims description 6
229940002612 prodrug Drugs 0.000 claims description 6
150000003839 salts Chemical class 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
125000001072 heteroaryl group Chemical class 0.000 claims description 5
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
WXAVSTZWKNIWCN-UHFFFAOYSA-N 1-(1-phenylethoxy)ethylbenzene Chemical compound C=1C=CC=CC=1C(C)OC(C)C1=CC=CC=C1 WXAVSTZWKNIWCN-UHFFFAOYSA-N 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
125000004404 heteroalkyl group Chemical class 0.000 claims description 2
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
235000019260 propionic acid Nutrition 0.000 claims description 2
125000003107 substituted aryl group Chemical group 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
239000000126 substance Substances 0.000 claims 11
PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims 1
GHGJTFTVXUKLSO-UHFFFAOYSA-N benzyl n-[1-[2-aminoethyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(CCN)C(=O)C(NC(=O)OCC=1C=CC=CC=1)CC1=CN=CN1 GHGJTFTVXUKLSO-UHFFFAOYSA-N 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
108010014186 ras Proteins Proteins 0.000 description 37
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230000012010 growth Effects 0.000 description 8
108090000623 proteins and genes Proteins 0.000 description 8
210000004027 cell Anatomy 0.000 description 7
235000018102 proteins Nutrition 0.000 description 7
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230000005764 inhibitory process Effects 0.000 description 6
230000035772 mutation Effects 0.000 description 6
235000001014 amino acid Nutrition 0.000 description 5
210000000170 cell membrane Anatomy 0.000 description 5
230000001419 dependent effect Effects 0.000 description 5
230000002246 oncogenic effect Effects 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
108010007508 Farnesyltranstransferase Proteins 0.000 description 4
102000007317 Farnesyltranstransferase Human genes 0.000 description 4
150000001413 amino acids Chemical class 0.000 description 4
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
231100000590 oncogenic Toxicity 0.000 description 4
230000035755 proliferation Effects 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
239000003558 transferase inhibitor Substances 0.000 description 4
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108091035707 Consensus sequence Proteins 0.000 description 3
241000699660 Mus musculus Species 0.000 description 3
208000009956 adenocarcinoma Diseases 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000004481 post-translational protein modification Effects 0.000 description 3
230000001323 posttranslational effect Effects 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
206010005003 Bladder cancer Diseases 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
206010009944 Colon cancer Diseases 0.000 description 2
102100022874 Dexamethasone-induced Ras-related protein 1 Human genes 0.000 description 2
241000282412 Homo Species 0.000 description 2
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229910052794 bromium Inorganic materials 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
230000032823 cell division Effects 0.000 description 2
230000004663 cell proliferation Effects 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
210000000172 cytosol Anatomy 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
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 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
238000011580 nude mouse model Methods 0.000 description 2
108010054353 p21(ras) farnesyl-protein transferase Proteins 0.000 description 2
230000013823 prenylation Effects 0.000 description 2
230000001131 transforming effect Effects 0.000 description 2
208000010570 urinary bladder carcinoma Diseases 0.000 description 2
230000002792 vascular Effects 0.000 description 2
ZIXDDEATQSBHHL-BEFAXECRSA-N (2S)-2-[[[4-[[(2R)-2-amino-3-mercaptopropyl]amino]-2-phenylphenyl]-oxomethyl]amino]-4-(methylthio)butanoic acid Chemical compound CSCC[C@@H](C(O)=O)NC(=O)C1=CC=C(NC[C@@H](N)CS)C=C1C1=CC=CC=C1 ZIXDDEATQSBHHL-BEFAXECRSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
208000003200 Adenoma Diseases 0.000 description 1
206010001233 Adenoma benign Diseases 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
101150047265 COR2 gene Proteins 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
VWFJDQUYCIWHTN-UHFFFAOYSA-N Farnesyl pyrophosphate Natural products CC(C)=CCCC(C)=CCCC(C)=CCOP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-UHFFFAOYSA-N 0.000 description 1
229940124226 Farnesyltransferase inhibitor Drugs 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
201000008808 Fibrosarcoma Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
101710113436 GTPase KRas Proteins 0.000 description 1
206010073069 Hepatic cancer Diseases 0.000 description 1
101000686227 Homo sapiens Ras-related protein R-Ras2 Proteins 0.000 description 1
206010023347 Keratoacanthoma Diseases 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
102000016397 Methyltransferase Human genes 0.000 description 1
108060004795 Methyltransferase Proteins 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
102000043276 Oncogene Human genes 0.000 description 1
229910018830 PO3H Inorganic materials 0.000 description 1
241001494479 Pecora Species 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
101710118538 Protease Proteins 0.000 description 1
108700020978 Proto-Oncogene Proteins 0.000 description 1
102000052575 Proto-Oncogene Human genes 0.000 description 1
241000287531 Psittacidae Species 0.000 description 1
101150040459 RAS gene Proteins 0.000 description 1
229940078123 Ras inhibitor Drugs 0.000 description 1
102100025003 Ras-related protein R-Ras2 Human genes 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
229910006069 SO3H Inorganic materials 0.000 description 1
101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
201000010208 Seminoma Diseases 0.000 description 1
241000282887 Suidae Species 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
229940123468 Transferase inhibitor Drugs 0.000 description 1
208000024248 Vascular System injury Diseases 0.000 description 1
208000012339 Vascular injury Diseases 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
125000003275 alpha amino acid group Chemical group 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
210000003679 cervix uteri Anatomy 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000007887 coronary angioplasty Methods 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000013171 endarterectomy Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
210000003238 esophagus Anatomy 0.000 description 1
208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
230000006126 farnesylation Effects 0.000 description 1
230000009123 feedback regulation Effects 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
108010050749 geranylgeranyltransferase type-I Proteins 0.000 description 1
208000005017 glioblastoma Diseases 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
239000000833 heterodimer Substances 0.000 description 1
125000001183 hydrocarbyl group Chemical group 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
208000003849 large cell carcinoma Diseases 0.000 description 1
201000002250 liver carcinoma Diseases 0.000 description 1
230000004807 localization Effects 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
201000005296 lung carcinoma Diseases 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
210000002464 muscle smooth vascular Anatomy 0.000 description 1
230000000869 mutational effect Effects 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
201000010198 papillary carcinoma Diseases 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
GOJZYSUJFPRACG-UHFFFAOYSA-N propan-2-yl 3-[[3-(1h-imidazol-5-yl)-2-(phenylmethoxycarbonylamino)propanoyl]-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]propanoate Chemical compound C=1N=CNC=1CC(NC(=O)OCC=1C=CC=CC=1)C(=O)N(CCC(=O)OC(C)C)CC(=O)NCC(C)(C)C1=CC=CC=C1 GOJZYSUJFPRACG-UHFFFAOYSA-N 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
108700042226 ras Genes Proteins 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
201000010174 renal carcinoma Diseases 0.000 description 1
210000003752 saphenous vein Anatomy 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
238000007892 surgical revascularization Methods 0.000 description 1
208000024891 symptom Diseases 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
230000001225 therapeutic effect Effects 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000030901 thyroid gland follicular carcinoma Diseases 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

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06147—Dipeptides with the first amino acid being heterocyclic and His-amino acid; Derivatives thereof
- 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
- 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
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyrrole Compounds (AREA)

ZA200006035A 1998-04-27 2000-10-26 Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors. ZA200006035B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US8325598P	1998-04-27	1998-04-27

Publications (1)

Publication Number	Publication Date
ZA200006035B true ZA200006035B (en)	2002-01-28

Family

ID=22177160

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200006035A ZA200006035B (en)	1998-04-27	2000-10-26	Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors.

Country Status (15)

Country	Link
US (1)	US6369034B1 (pt)
EP (1)	EP1076663B1 (pt)
JP (1)	JP2002513031A (pt)
KR (1)	KR20010043035A (pt)
AT (1)	ATE259826T1 (pt)
AU (1)	AU759492B2 (pt)
BR (1)	BR9909961A (pt)
CA (1)	CA2322944C (pt)
DE (1)	DE69914893T2 (pt)
DK (1)	DK1076663T3 (pt)
ES (1)	ES2214021T3 (pt)
NZ (1)	NZ507165A (pt)
PT (1)	PT1076663E (pt)
WO (1)	WO1999055725A1 (pt)
ZA (1)	ZA200006035B (pt)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6316436B1 (en)	1998-12-08	2001-11-13	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
WO2000034437A2 (en)	1998-12-08	2000-06-15	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
US7425618B2 (en)	2002-06-14	2008-09-16	Medimmune, Inc.	Stabilized anti-respiratory syncytial virus (RSV) antibody formulations
US7132100B2 (en)	2002-06-14	2006-11-07	Medimmune, Inc.	Stabilized liquid anti-RSV antibody formulations
EP1539234A4 (en) *	2002-09-05	2006-02-15	Medimmune Inc	METHOD FOR PREVENTING OR TREATING CELL MALIGNITY BY ADMINISTERING CD2 ANTAGONISTS
US8034831B2 (en) *	2002-11-06	2011-10-11	Celgene Corporation	Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies
US7563810B2 (en)	2002-11-06	2009-07-21	Celgene Corporation	Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases
JP3837633B2 (ja) *	2002-11-19	2006-10-25	株式会社クレディアジャパン	新規な機能性ペプチド核酸およびその製法
WO2004091510A2 (en)	2003-04-11	2004-10-28	Medimmune, Inc.	Recombinant il-9 antibodies and uses thereof
DE10326303A1 (de) *	2003-06-11	2004-12-30	Celares Gmbh	Reagenzien zur Modifikation von Biopharmazeutika, deren Herstellung und Anwendung
US20060228350A1 (en) *	2003-08-18	2006-10-12	Medimmune, Inc.	Framework-shuffling of antibodies
CA2536238C (en)	2003-08-18	2015-04-07	Medimmune, Inc.	Humanization of antibodies
CA2585717A1 (en)	2004-10-27	2006-05-04	Medimmune Inc.	Modulation of antibody specificity by tailoring the affinity to cognate antigens
EP1869192B1 (en)	2005-03-18	2016-01-20	MedImmune, LLC	Framework-shuffling of antibodies
US8987306B2 (en) *	2005-06-07	2015-03-24	The Trustees Of The University Of Pennsylvania	Inhibitors of integrin alpha2beta1 based on prolyl diaminopropionic acid scaffold
AU2006254936A1 (en) *	2005-06-07	2006-12-14	The Trustees Of The University Of Pennesylvania	Inhibitors of the alpha2beta1/GPIa-IIa integrin
KR20080025174A (ko)	2005-06-23	2008-03-19	메디뮨 인코포레이티드	응집 및 단편화 프로파일이 최적화된 항체 제제
WO2007027742A2 (en) *	2005-08-31	2007-03-08	The Trustees Of The University Of Pennsylvania	SMALL MOLECULE INTEGRIN α2βl/GPIa-IIa ANTAGONISTS
KR101314362B1 (ko)	2006-08-28	2013-10-10	라 졸라 인스티튜트 포 앨러지 앤드 이뮤놀로지	길항성 인간 ｌｉｇｈｔ-특이적 인간 모노클로날 항체
US20100209434A1 (en)	2007-03-30	2010-08-19	Medimmune, Llc	Antibody formulation
BRPI0818810A2 (pt)	2007-10-31	2014-10-29	Medimmune Llc	Esqueletos d polipeptídeo recombinante e multimérico, molécula de ácido n ucleico isolado, vetor de expressão, célula hospedeira, biblioteca de exibição de polipeptídeo, coleção de moléculas de ácido nucleico isolado, métodos para obter um esqueleto de polipeptídeo e pelo menos dois esqueletos, para detectar um composto em uma amostra, para capturar um composto em uma amostra, para prevenir, tratar, controlar ou melhorar uma doença, para diagnose ou formação de imagem de uma doença para purificar e produzir um esqueleto, para ensaiar ou detectar a ligação de um esqueleto a um alvo, para usar o esqueleto e para prevenir, tratar, melhora ou controlar câncer, composição estéril, isenta de pirógeno, composição farmacêutica, e, processo escalável.
US9540443B2 (en)	2011-01-26	2017-01-10	Kolltan Pharmaceuticals, Inc.	Anti-kit antibodies
NZ731881A (en)	2012-07-25	2022-07-29	Celldex Therapeutics Inc	Anti-kit antibodies and uses thereof
CA2887129A1 (en)	2012-10-09	2014-04-17	Igenica, Inc.	Anti-c16orf54 antibodies and methods of use thereof
JP6824735B2 (ja)	2013-06-06	2021-02-03	ピエール、ファーブル、メディカマン	抗Ｃ１０ｏｒｆ５４抗体およびその使用方法
AU2014332442B2 (en)	2013-08-26	2019-12-19	Biontech Research And Development, Inc.	Nucleic acids encoding human antibodies to Sialyl-Lewis
GB201403775D0 (en)	2014-03-04	2014-04-16	Kymab Ltd	Antibodies, uses & methods
KR102614642B1 (ko)	2014-06-04	2023-12-19	바이오엔테크 리서치 앤드 디벨롭먼트 인코포레이티드	강글리오사이드 ｇｄ２에 대한 사람 단클론 항체
SI3333191T1 (sl)	2014-12-11	2021-03-31	Pierre Fabre Medicament	Proti C10ORF54 protitelesa in uporaba le-teh
CN114504652A (zh)	2015-03-03	2022-05-17	科马布有限公司	抗体、用途和方法
EP3383908A1 (en)	2015-12-02	2018-10-10	Stsciences, Inc.	Antibodies specific to glycosylated btla (b- and t- lymphocyte attenuator)
KR102803158B1 (ko)	2015-12-02	2025-05-08	주식회사 에스티큐브앤컴퍼니	Btn1a1에 면역특이적으로 결합하는 항체와 분자 및 그의 치료 용도
US11779604B2 (en)	2016-11-03	2023-10-10	Kymab Limited	Antibodies, combinations comprising antibodies, biomarkers, uses and methods
JP7369038B2 (ja)	2017-05-31	2023-10-25	ストキューブアンドシーオー．，インコーポレイテッド	Ｂｔｎ１ａ１に免疫特異的に結合する抗体及び分子並びにその治療的使用
JP7768666B2 (ja)	2017-05-31	2025-11-12	ストキューブアンドシーオー．，インコーポレイテッド	Ｂｔｎ１ａ１に免疫特異的に結合する抗体及び分子を用いて癌を治療する方法
CN121248782A (zh)	2017-06-06	2026-01-02	斯特库伯株式会社	使用结合btn1a1或btn1a1-配体的抗体和分子治疗癌症的方法
CN111630069B (zh)	2017-10-13	2024-05-31	勃林格殷格翰国际有限公司	针对Thomsen-nouvelle(Tn)抗原的人抗体
IL280199B2 (en)	2018-07-20	2025-08-01	Pf Medicament	Receptor for vista
EP4185284A4 (en) *	2020-07-22	2025-08-27	Parabilis Medicines Inc	AMINO ACIDS

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5576293A (en)	1993-09-30	1996-11-19	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
NZ275691A (en) *	1993-11-05	1998-03-25	Warner Lambert Co	Di and tripeptides and compositions thereof which inhibit farnesyl transferase
US5571792A (en)	1994-06-30	1996-11-05	Warner-Lambert Company	Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase
EA199801031A1 (ru) *	1996-05-22	1999-06-24	Варнер-Ламберт Компани	Ингибиторы протеинфарнезилтрансферазы
PE46999A1 (es)	1996-12-17	1999-05-20	Warner Lambert Co	Inhibidores de cicloalquilo de la enzima farnesiltransferasa de las proteinas
WO1998046625A1 (en)	1997-04-11	1998-10-22	Warner-Lambert Company	Dipeptide inhibitors of protein farnesyltransferase

1999
- 1999-03-19 AU AU33587/99A patent/AU759492B2/en not_active Ceased
- 1999-03-19 JP JP2000545883A patent/JP2002513031A/ja active Pending
- 1999-03-19 DK DK99914958T patent/DK1076663T3/da active
- 1999-03-19 ES ES99914958T patent/ES2214021T3/es not_active Expired - Lifetime
- 1999-03-19 PT PT99914958T patent/PT1076663E/pt unknown
- 1999-03-19 WO PCT/US1999/006090 patent/WO1999055725A1/en not_active Ceased
- 1999-03-19 BR BR9909961-6A patent/BR9909961A/pt not_active IP Right Cessation
- 1999-03-19 CA CA002322944A patent/CA2322944C/en not_active Expired - Fee Related
- 1999-03-19 AT AT99914958T patent/ATE259826T1/de not_active IP Right Cessation
- 1999-03-19 EP EP99914958A patent/EP1076663B1/en not_active Expired - Lifetime
- 1999-03-19 KR KR1020007011897A patent/KR20010043035A/ko not_active Withdrawn
- 1999-03-19 US US09/646,147 patent/US6369034B1/en not_active Expired - Fee Related
- 1999-03-19 NZ NZ507165A patent/NZ507165A/xx unknown
- 1999-03-19 DE DE69914893T patent/DE69914893T2/de not_active Expired - Fee Related
2000
- 2000-10-26 ZA ZA200006035A patent/ZA200006035B/en unknown

Also Published As

Publication number	Publication date
WO1999055725A1 (en)	1999-11-04
AU3358799A (en)	1999-11-16
DE69914893T2 (de)	2004-07-22
EP1076663A1 (en)	2001-02-21
PT1076663E (pt)	2004-06-30
ES2214021T3 (es)	2004-09-01
US6369034B1 (en)	2002-04-09
CA2322944A1 (en)	1999-11-04
CA2322944C (en)	2003-05-20
DE69914893D1 (de)	2004-03-25
JP2002513031A (ja)	2002-05-08
BR9909961A (pt)	2000-12-26
AU759492B2 (en)	2003-04-17
KR20010043035A (ko)	2001-05-25
DK1076663T3 (da)	2004-06-01
ATE259826T1 (de)	2004-03-15
NZ507165A (en)	2003-06-30
EP1076663B1 (en)	2004-02-18

Publication	Publication Date	Title
ZA200006035B (en)	2002-01-28	Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors.
US6300501B1 (en)	2001-10-09	Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase
SK161098A3 (en)	2000-06-12	Inhibitors of protein farnesyl transferase
JP3929069B2 (ja)	2007-06-13	プレニルトランスフェラーゼの阻害剤
WO1997026246A1 (en)	1997-07-24	Substituted histidine inhibitors of protein farnesyltransferase
US6265382B1 (en)	2001-07-24	Dipeptide inhibitors of protein farnesyltransferase
US6492410B1 (en)	2002-12-10	Combinations of protein farnesyltransferase and HMG CoA reductase inhibitors and their use to treat cancer
US6281194B1 (en)	2001-08-28	Cycloalkyl inhibitors of protein farnesyltransferase
US6737410B1 (en)	2004-05-18	Inhibitors of protein farnesyl transferase
PT91545A (pt)	1990-03-08	Processo para a preparacao de aminometil-peptideos, uteis como medicamentos
MXPA00009613A (en)	2001-07-31	Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors
ZA200006491B (en)	2002-05-09	Combinations of protein farnesyltransferase and HMG CoA reductase inhibitors and their use to treat cancer.
MXPA99001592A (es)	1999-09-20	Inhibidores cicloalquilo de proteina farnesiltransferasa
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
KR20000015892A (ko)	2000-03-15	단백질 파르네실 트랜스퍼라제의 억제제