UA75660C2 - Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (mtp) and/or apolipoprotein b (apo b) secretion - Google Patents

Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (mtp) and/or apolipoprotein b (apo b) secretion Download PDF

Info

Publication number: UA75660C2
Authority: UA; Ukraine
Prior art keywords: alkyl; independently; methyl; phenyl; trifluoromethyl
Prior art date: 2001-06-28

Application number

UA20031212657A

Other languages

English (en)

Ukrainian (uk)

Inventor

Alan Elwood Blize

Brian Scott Bronk

Clive Philip Mason

Original Assignee

Pfizer Prod Inc

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.)

2001-06-28

Filing date

2002-05-24

Publication date

2006-05-15

2002-05-24 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2006-05-15 Publication of UA75660C2 publication Critical patent/UA75660C2/uk

Links

239000003112 inhibitor Substances 0.000 title abstract description 45
102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 title description 17
230000028327 secretion Effects 0.000 title description 8
150000002475 indoles Chemical class 0.000 title description 7
101710095342 Apolipoprotein B Proteins 0.000 title description 2
102100040202 Apolipoprotein B-100 Human genes 0.000 title description 2
108010038232 microsomal triglyceride transfer protein Proteins 0.000 title description 2
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical class C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title 1
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 352
238000000034 method Methods 0.000 claims abstract description 126
208000008589 Obesity Diseases 0.000 claims abstract description 17
235000020824 obesity Nutrition 0.000 claims abstract description 17
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims description 197
-1 nitro, azido, amino, hydroxy Chemical group 0.000 claims description 115
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 73
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 70
125000001424 substituent group Chemical group 0.000 claims description 70
150000003839 salts Chemical class 0.000 claims description 65
229910052736 halogen Inorganic materials 0.000 claims description 60
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
150000002367 halogens Chemical class 0.000 claims description 49
125000000753 cycloalkyl group Chemical group 0.000 claims description 46
239000002253 acid Substances 0.000 claims description 40
230000015572 biosynthetic process Effects 0.000 claims description 38
241001465754 Metazoa Species 0.000 claims description 33
150000001408 amides Chemical class 0.000 claims description 33
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 29
125000003545 alkoxy group Chemical group 0.000 claims description 28
125000000623 heterocyclic group Chemical group 0.000 claims description 28
125000004076 pyridyl group Chemical group 0.000 claims description 27
125000003342 alkenyl group Chemical group 0.000 claims description 26
125000000304 alkynyl group Chemical group 0.000 claims description 24
229910052799 carbon Inorganic materials 0.000 claims description 24
239000004305 biphenyl Substances 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 21
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
125000004429 atom Chemical group 0.000 claims description 18
125000001072 heteroaryl group Chemical group 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 18
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 16
125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
239000003085 diluting agent Substances 0.000 claims description 14
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 13
125000002950 monocyclic group Chemical group 0.000 claims description 13
125000004414 alkyl thio group Chemical group 0.000 claims description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
229910052796 boron Inorganic materials 0.000 claims description 11
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
125000003282 alkyl amino group Chemical group 0.000 claims description 10
125000004663 dialkyl amino group Chemical group 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 8
150000001602 bicycloalkyls Chemical group 0.000 claims description 8
230000003993 interaction Effects 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 7
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 7
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 7
125000006530 (C4-C6) alkyl group Chemical group 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 5
230000007062 hydrolysis Effects 0.000 claims description 5
238000006460 hydrolysis reaction Methods 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 4
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
YEKJABDQUZLZOA-UHFFFAOYSA-N 2-amino-n-methyl-2-phenylacetamide Chemical compound CNC(=O)C(N)C1=CC=CC=C1 YEKJABDQUZLZOA-UHFFFAOYSA-N 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
125000001041 indolyl group Chemical group 0.000 claims description 3
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125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
230000008569 process Effects 0.000 abstract description 38
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
150000002632 lipids Chemical class 0.000 abstract description 2
102000018616 Apolipoproteins B Human genes 0.000 abstract 1
108010027006 Apolipoproteins B Proteins 0.000 abstract 1
239000000203 mixture Substances 0.000 description 124
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
239000000243 solution Substances 0.000 description 93
239000002904 solvent Substances 0.000 description 74
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
239000000047 product Substances 0.000 description 62
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
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239000007787 solid Substances 0.000 description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 26
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
235000019439 ethyl acetate Nutrition 0.000 description 25
238000005755 formation reaction Methods 0.000 description 25
150000001412 amines Chemical class 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
238000007792 addition Methods 0.000 description 21
239000000843 powder Substances 0.000 description 21
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 21
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000000725 suspension Substances 0.000 description 18
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238000001914 filtration Methods 0.000 description 16
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229920006395 saturated elastomer Polymers 0.000 description 16
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
239000000523 sample Substances 0.000 description 14
238000003756 stirring Methods 0.000 description 14
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 13
238000002441 X-ray diffraction Methods 0.000 description 13
239000003054 catalyst Substances 0.000 description 13
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 13
238000004128 high performance liquid chromatography Methods 0.000 description 13
229940002612 prodrug Drugs 0.000 description 13
239000000651 prodrug Substances 0.000 description 13
230000002829 reductive effect Effects 0.000 description 13
238000012360 testing method Methods 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
108090000854 Oxidoreductases Proteins 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
239000007864 aqueous solution Substances 0.000 description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
206010012601 diabetes mellitus Diseases 0.000 description 12
238000002955 isolation Methods 0.000 description 12
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238000001953 recrystallisation Methods 0.000 description 11
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210000002966 serum Anatomy 0.000 description 11
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241000699670 Mus sp. Species 0.000 description 10
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
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RGXUCUWVGKLACF-UHFFFAOYSA-N (3-methylphenyl)methanamine Chemical group CC1=CC=CC(CN)=C1 RGXUCUWVGKLACF-UHFFFAOYSA-N 0.000 description 9
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XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
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NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
201000001320 Atherosclerosis Diseases 0.000 description 7
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Classifications

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- 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
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
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- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Obesity (AREA)
Hematology (AREA)
Diabetes (AREA)
Child & Adolescent Psychology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Furan Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Hydrogenated Pyridines (AREA)

UA20031212657A 2001-06-28 2002-05-24 Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (mtp) and/or apolipoprotein b (apo b) secretion UA75660C2 (en)

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US30164401P	2001-06-28	2001-06-28
PCT/IB2002/001876 WO2003002533A1 (en)	2001-06-28	2002-05-24	Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (mtp) and/or apolipoprotein b (apo b) secretion

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US (5)	US6720351B2 (es)
EP (1)	EP1404653B1 (es)
JP (1)	JP4139325B2 (es)
KR (2)	KR100575944B1 (es)
CN (2)	CN1522246B (es)
AP (1)	AP1649A (es)
AR (1)	AR036158A1 (es)
AT (1)	ATE405548T1 (es)
AU (1)	AU2002307839B2 (es)
BG (1)	BG108487A (es)
BR (1)	BR0210616A (es)
CA (1)	CA2451474C (es)
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GE (2)	GEP20063720B (es)
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HR (1)	HRP20031051B1 (es)
HU (1)	HU229551B1 (es)
IL (1)	IL158516A0 (es)
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MA (1)	MA27045A1 (es)
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MY (1)	MY129328A (es)
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JP4564713B2 (ja)	2000-11-01	2010-10-20	ミレニアム・ファーマシューティカルズ・インコーポレイテッド	窒素性複素環式化合物、ならびに窒素性複素環式化合物およびその中間体を作製するための方法
KR100575944B1 (ko) *	2001-06-28	2006-05-02	화이자 프로덕츠 인코포레이티드	미소체 트리글리세라이드 전달 단백질(ｍｔｐ) 및/또는아포지방단백질 ｂ(ａｐｏｂ)분비의 억제제로서의트리아미드-치환된 인돌, 벤조푸란 및 벤조티오펜
ATE536993T1 (de) *	2002-01-02	2011-12-15	Visen Medical Inc	Aminfunktionalisierte superparamagnetisierte nanoteilchen für die synthese von biokonjugaten
CN1964630A (zh) *	2003-02-13	2007-05-16	耶希瓦大学艾伯塔·爱恩斯坦医学院	通过控制下丘脑的长链脂肪酰基－辅酶A(LC－CoA)的水平来调控食物摄取和葡萄糖产生
WO2004112695A2 (en) *	2003-05-20	2004-12-29	Erimos Pharmaceutical Llc	Methods and compositions for delivery of catecholic butanes for treatment of obesity
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Publication number	Publication date
OA12626A (en)	2006-06-13
HU229551B1 (hu)	2014-01-28
ES2307799T3 (es)	2008-12-01
US20050288335A1 (en)	2005-12-29
AR036158A1 (es)	2004-08-18
US20040087625A1 (en)	2004-05-06
EE200400040A (et)	2004-06-15
KR100575919B1 (ko)	2006-05-02
IS2603B (is)	2010-04-15
JP2004537541A (ja)	2004-12-16
AP2002002567A0 (en)	2002-06-30
DK1404653T3 (da)	2008-10-06
UY27360A1 (es)	2003-01-31
MXPA03011707A (es)	2004-03-19
HRP20031051A2 (en)	2005-08-31
US6720351B2 (en)	2004-04-13
CZ20033558A3 (cs)	2004-04-14
MY129328A (en)	2007-03-30
RS100403A (sr)	2007-02-05
CA2451474C (en)	2009-06-16
CN1522246A (zh)	2004-08-18
DE60228447D1 (de)	2008-10-02
US7348355B2 (en)	2008-03-25
US20060194772A1 (en)	2006-08-31
WO2003002533A1 (en)	2003-01-09
BR0210616A (pt)	2004-09-28
EE05452B1 (et)	2011-08-15
US6949572B2 (en)	2005-09-27
CY1108407T1 (el)	2014-02-12
RS50712B (sr)	2010-06-30
IS6988A (is)	2003-10-09
PA8549301A1 (es)	2003-02-14
NZ528752A (en)	2006-06-30
EA007008B1 (ru)	2006-06-30
ATE405548T1 (de)	2008-09-15
KR20040013006A (ko)	2004-02-11
JP4139325B2 (ja)	2008-08-27
US20050080108A1 (en)	2005-04-14
IL158516A0 (en)	2004-05-12
PE20030135A1 (es)	2003-03-03
SK16102003A3 (sk)	2004-08-03
HRP20031051B1 (en)	2012-01-31
HUP0400348A3 (en)	2011-07-28
US6979692B2 (en)	2005-12-27
NO326700B1 (no)	2009-02-02
KR20060006107A (ko)	2006-01-18
NO20035607D0 (no)	2003-12-16
CN1880304B (zh)	2010-11-24
CN1522246B (zh)	2010-04-21
AP1649A (en)	2006-08-07
PL367680A1 (en)	2005-03-07
GEP20063720B (en)	2006-01-10
EP1404653A1 (en)	2004-04-07
MA27045A1 (fr)	2004-12-20
ECSP034925A (es)	2004-02-26
GT200200136A (es)	2003-05-15
EP1404653B1 (en)	2008-08-20
GEP20053720B (en)	2006-01-10
CR7151A (es)	2004-02-23
HK1064369A1 (zh)	2005-01-28
KR100575944B1 (ko)	2006-05-02
US20030187053A1 (en)	2003-10-02
HUP0400348A2 (hu)	2004-12-28
EA200301310A1 (ru)	2004-06-24
CA2451474A1 (en)	2003-01-09
HK1096665A1 (en)	2007-06-08
US7482368B2 (en)	2009-01-27
SI1404653T1 (sl)	2008-12-31
TNSN03146A1 (fr)	2005-12-23
TW200628447A (en)	2006-08-16
BG108487A (bg)	2005-04-30
SK287806B6 (sk)	2011-10-04
CN1880304A (zh)	2006-12-20
ZA200307818B (en)	2004-10-07
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PT1404653E (pt)	2008-09-23
AU2002307839B2 (en)	2006-03-16

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