SK7362003A3 - 4-(Biphenylcarbonylamino)piperidine derivatives as MTP inhibitors - Google Patents

4-(Biphenylcarbonylamino)piperidine derivatives as MTP inhibitors Download PDF

Info

Publication number: SK7362003A3
Authority: SK; Slovakia
Prior art keywords: biphenyl; piperidine; carbonylamino; methyl; formula
Prior art date: 2000-11-23

Application number

SK736-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Alyx-Caroline Guevel

Didier Festal

Francois Collonges

Daniel Guerrier

Oliver Chevreuil

Original Assignee

Merck Patent Gmbh

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.)

2000-11-23

Filing date

2001-10-25

Publication date

2003-11-04

2001-10-25 Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh

2003-11-04 Publication of SK7362003A3 publication Critical patent/SK7362003A3/sk

Links

239000003112 inhibitor Substances 0.000 title claims abstract description 9
UGTSHKSSLJCDTJ-UHFFFAOYSA-N 2-phenyl-n-piperidin-4-ylbenzamide Chemical class C=1C=CC=C(C=2C=CC=CC=2)C=1C(=O)NC1CCNCC1 UGTSHKSSLJCDTJ-UHFFFAOYSA-N 0.000 title claims description 7
150000001875 compounds Chemical class 0.000 claims abstract description 139
102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims abstract description 26
108010038232 microsomal triglyceride transfer protein Proteins 0.000 claims abstract description 25
230000028327 secretion Effects 0.000 claims abstract description 19
125000003118 aryl group Chemical group 0.000 claims abstract description 14
150000003839 salts Chemical class 0.000 claims abstract description 14
102000006410 Apoproteins Human genes 0.000 claims abstract description 9
108010083590 Apoproteins Proteins 0.000 claims abstract description 9
125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
125000005493 quinolyl group Chemical group 0.000 claims abstract description 8
239000004305 biphenyl Substances 0.000 claims abstract description 5
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims abstract description 5
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
125000004951 trihalomethoxy group Chemical group 0.000 claims abstract description 3
125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 125
-1 2-quinolyl Chemical group 0.000 claims description 94
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 60
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
238000000034 method Methods 0.000 claims description 26
238000002360 preparation method Methods 0.000 claims description 26
125000004432 carbon atom Chemical group C* 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
239000003638 chemical reducing agent Substances 0.000 claims description 12
239000008194 pharmaceutical composition Substances 0.000 claims description 12
150000001412 amines Chemical class 0.000 claims description 10
230000008569 process Effects 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 9
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 claims description 8
229910052783 alkali metal Inorganic materials 0.000 claims description 8
150000001340 alkali metals Chemical group 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
201000001320 Atherosclerosis Diseases 0.000 claims description 7
125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 5
208000035150 Hypercholesterolemia Diseases 0.000 claims description 5
208000008589 Obesity Diseases 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
208000006575 hypertriglyceridemia Diseases 0.000 claims description 5
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
235000020824 obesity Nutrition 0.000 claims description 5
239000012453 solvate Substances 0.000 claims description 5
LNNVAYYTCGGEGA-UHFFFAOYSA-N 2-phenyl-n-[1-(quinolin-2-ylmethyl)piperidin-4-yl]benzamide Chemical compound C1CN(CC=2N=C3C=CC=CC3=CC=2)CCC1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 LNNVAYYTCGGEGA-UHFFFAOYSA-N 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
208000032928 Dyslipidaemia Diseases 0.000 claims description 4
208000031226 Hyperlipidaemia Diseases 0.000 claims description 4
208000017170 Lipid metabolism disease Diseases 0.000 claims description 4
206010033645 Pancreatitis Diseases 0.000 claims description 4
206010012601 diabetes mellitus Diseases 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
150000004820 halides Chemical class 0.000 claims description 4
150000004677 hydrates Chemical class 0.000 claims description 4
201000001421 hyperglycemia Diseases 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000006267 biphenyl group Chemical group 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
RFJKDTNICCJFRS-UHFFFAOYSA-N n-[1-[(6-methylpyridin-2-yl)methyl]piperidin-4-yl]-2-phenylbenzamide Chemical compound CC1=CC=CC(CN2CCC(CC2)NC(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 RFJKDTNICCJFRS-UHFFFAOYSA-N 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 abstract 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
235000010290 biphenyl Nutrition 0.000 abstract 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
125000005309 thioalkoxy group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
229910052739 hydrogen Inorganic materials 0.000 description 43
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
238000006243 chemical reaction Methods 0.000 description 31
239000000203 mixture Substances 0.000 description 30
239000000243 solution Substances 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
230000005764 inhibitory process Effects 0.000 description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
102000018616 Apolipoproteins B Human genes 0.000 description 14
108010027006 Apolipoproteins B Proteins 0.000 description 14
239000002585 base Substances 0.000 description 14
229910052938 sodium sulfate Inorganic materials 0.000 description 14
235000011152 sodium sulphate Nutrition 0.000 description 14
239000007787 solid Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 12
238000005481 NMR spectroscopy Methods 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
239000002253 acid Substances 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical class [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
239000000377 silicon dioxide Substances 0.000 description 9
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
108010062497 VLDL Lipoproteins Proteins 0.000 description 8
238000001914 filtration Methods 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
150000001299 aldehydes Chemical class 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
230000000694 effects Effects 0.000 description 6
125000001072 heteroaryl group Chemical group 0.000 description 6
229910052740 iodine Inorganic materials 0.000 description 6
239000012429 reaction media Substances 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
229960001701 chloroform Drugs 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
KQXKFXOUSCSLQC-UHFFFAOYSA-N n-[1-[(6-fluoroquinolin-2-yl)methyl]piperidin-4-yl]-2-phenylbenzamide Chemical compound C1=CC2=CC(F)=CC=C2N=C1CN(CC1)CCC1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 KQXKFXOUSCSLQC-UHFFFAOYSA-N 0.000 description 5
239000002245 particle Substances 0.000 description 5
229920000728 polyester Polymers 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
235000011121 sodium hydroxide Nutrition 0.000 description 5
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
239000007983 Tris buffer Substances 0.000 description 4
125000003342 alkenyl group Chemical group 0.000 description 4
125000003368 amide group Chemical group 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
238000000605 extraction Methods 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
229910052500 inorganic mineral Inorganic materials 0.000 description 4
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
235000010755 mineral Nutrition 0.000 description 4
239000011707 mineral Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
239000012071 phase Substances 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
235000011118 potassium hydroxide Nutrition 0.000 description 4
239000000843 powder Substances 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000000926 separation method Methods 0.000 description 4
239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
SVIRKOCSSOKHBX-UHFFFAOYSA-N 2,2,2-trifluoro-n-piperidin-4-ylacetamide Chemical compound FC(F)(F)C(=O)NC1CCNCC1 SVIRKOCSSOKHBX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
102000004895 Lipoproteins Human genes 0.000 description 3
108090001030 Lipoproteins Proteins 0.000 description 3
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
150000001638 boron Chemical class 0.000 description 3
150000001718 carbodiimides Chemical class 0.000 description 3
238000001816 cooling Methods 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
238000001035 drying Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000008187 granular material Substances 0.000 description 3
230000002440 hepatic effect Effects 0.000 description 3
125000004446 heteroarylalkyl group Chemical group 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
239000002502 liposome Substances 0.000 description 3
210000004185 liver Anatomy 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000003880 polar aprotic solvent Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
WPYJKGWLDJECQD-UHFFFAOYSA-N quinoline-2-carbaldehyde Chemical compound C1=CC=CC2=NC(C=O)=CC=C21 WPYJKGWLDJECQD-UHFFFAOYSA-N 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
238000012546 transfer Methods 0.000 description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
238000005406 washing Methods 0.000 description 3
CCODOIDFURPJTR-BTJKTKAUSA-N (Z)-but-2-enedioic acid piperidine Chemical compound C1CCNCC1.OC(=O)\C=C/C(O)=O CCODOIDFURPJTR-BTJKTKAUSA-N 0.000 description 2
CCODOIDFURPJTR-WLHGVMLRSA-N (e)-but-2-enedioic acid;piperidine Chemical compound C1CCNCC1.OC(=O)\C=C\C(O)=O CCODOIDFURPJTR-WLHGVMLRSA-N 0.000 description 2
CDDDRVNOHLVEED-UHFFFAOYSA-N 1-cyclohexyl-3-[1-[[1-(cyclohexylcarbamoylamino)cyclohexyl]diazenyl]cyclohexyl]urea Chemical compound C1CCCCC1(N=NC1(CCCCC1)NC(=O)NC1CCCCC1)NC(=O)NC1CCCCC1 CDDDRVNOHLVEED-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 2
UGPQPVWABPCSIP-UHFFFAOYSA-N 2-(bromomethyl)-6-fluoroquinoline Chemical compound N1=C(CBr)C=CC2=CC(F)=CC=C21 UGPQPVWABPCSIP-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
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Classifications

- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Child & Adolescent Psychology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)

SK736-2003A 2000-11-23 2001-10-25 4-(Biphenylcarbonylamino)piperidine derivatives as MTP inhibitors SK7362003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR0015143A FR2816940A1 (fr)	2000-11-23	2000-11-23	Derives de 4-(biphenylcarbonylamino)-piperidine, compositions les contenant et leur utilisation
PCT/EP2001/012326 WO2002042291A1 (en)	2000-11-23	2001-10-25	4-(biphenylcarbonylamino)piperidine derivatives as mtp inhibitors

Publications (1)

Publication Number	Publication Date
SK7362003A3 true SK7362003A3 (en)	2003-11-04

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ID=8856805

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK736-2003A SK7362003A3 (en)	2000-11-23	2001-10-25	4-(Biphenylcarbonylamino)piperidine derivatives as MTP inhibitors

Country Status (20)

Country	Link
US (1)	US20040034028A1 (es)
EP (1)	EP1335912A1 (es)
JP (1)	JP2004514676A (es)
KR (1)	KR20030060954A (es)
CN (1)	CN1476445A (es)
AR (1)	AR031499A1 (es)
AU (1)	AU2002221745A1 (es)
BR (1)	BR0115520A (es)
CA (1)	CA2429326A1 (es)
CZ (1)	CZ20031619A3 (es)
FR (1)	FR2816940A1 (es)
HU (1)	HUP0400819A2 (es)
IL (1)	IL155986A0 (es)
MX (1)	MXPA03004540A (es)
NO (1)	NO20032315L (es)
PE (1)	PE20020595A1 (es)
PL (1)	PL365939A1 (es)
RU (1)	RU2003117458A (es)
SK (1)	SK7362003A3 (es)
WO (1)	WO2002042291A1 (es)

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FR2871463B1 (fr) *	2004-06-11	2006-09-22	Merck Sante Soc Par Actions Si	Derives a structure aroyl-o-piperidine, leurs procedes de preparation, les compositions pharmaceutiques qui les contiennent et leurs applications en therapeutique
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2000
- 2000-11-23 FR FR0015143A patent/FR2816940A1/fr not_active Withdrawn
2001
- 2001-10-25 WO PCT/EP2001/012326 patent/WO2002042291A1/en not_active Ceased
- 2001-10-25 SK SK736-2003A patent/SK7362003A3/sk unknown
- 2001-10-25 US US10/432,323 patent/US20040034028A1/en not_active Abandoned
- 2001-10-25 KR KR10-2003-7006923A patent/KR20030060954A/ko not_active Withdrawn
- 2001-10-25 CN CNA018192866A patent/CN1476445A/zh active Pending
- 2001-10-25 MX MXPA03004540A patent/MXPA03004540A/es unknown
- 2001-10-25 HU HU0400819A patent/HUP0400819A2/hu unknown
- 2001-10-25 CA CA002429326A patent/CA2429326A1/en not_active Abandoned
- 2001-10-25 CZ CZ20031619A patent/CZ20031619A3/cs unknown
- 2001-10-25 BR BR0115520-2A patent/BR0115520A/pt not_active Application Discontinuation
- 2001-10-25 IL IL15598601A patent/IL155986A0/xx unknown
- 2001-10-25 EP EP01997486A patent/EP1335912A1/en not_active Withdrawn
- 2001-10-25 PL PL01365939A patent/PL365939A1/xx unknown
- 2001-10-25 RU RU2003117458/04A patent/RU2003117458A/ru not_active Application Discontinuation
- 2001-10-25 AU AU2002221745A patent/AU2002221745A1/en not_active Abandoned
- 2001-10-25 JP JP2002544425A patent/JP2004514676A/ja active Pending
- 2001-11-23 PE PE2001001175A patent/PE20020595A1/es not_active Application Discontinuation
- 2001-11-23 AR ARP010105460A patent/AR031499A1/es unknown
2003
- 2003-05-22 NO NO20032315A patent/NO20032315L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
BR0115520A (pt)	2003-09-16
AR031499A1 (es)	2003-09-24
US20040034028A1 (en)	2004-02-19
KR20030060954A (ko)	2003-07-16
CZ20031619A3 (cs)	2003-09-17
JP2004514676A (ja)	2004-05-20
CA2429326A1 (en)	2002-05-30
PL365939A1 (en)	2005-01-24
EP1335912A1 (en)	2003-08-20
NO20032315D0 (no)	2003-05-22
RU2003117458A (ru)	2004-12-27
WO2002042291A1 (en)	2002-05-30
FR2816940A1 (fr)	2002-05-24
PE20020595A1 (es)	2002-07-08
IL155986A0 (en)	2003-12-23
HUP0400819A2 (hu)	2004-07-28
CN1476445A (zh)	2004-02-18
NO20032315L (no)	2003-05-22
AU2002221745A1 (en)	2002-06-03
MXPA03004540A (es)	2003-09-10

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