ZA200205012B - Substituted piperazine derivatives as MTP inhibitors. - Google Patents
Substituted piperazine derivatives as MTP inhibitors. Download PDFInfo
- Publication number
- ZA200205012B ZA200205012B ZA200205012A ZA200205012A ZA200205012B ZA 200205012 B ZA200205012 B ZA 200205012B ZA 200205012 A ZA200205012 A ZA 200205012A ZA 200205012 A ZA200205012 A ZA 200205012A ZA 200205012 B ZA200205012 B ZA 200205012B
- Authority
- ZA
- South Africa
- Prior art keywords
- group
- alkyl
- phenyl
- denotes
- butyl
- Prior art date
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- 150000004885 piperazines Chemical class 0.000 title claims description 8
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title claims description 8
- 239000003112 inhibitor Substances 0.000 title description 8
- -1 methylene, ethylene, imino Chemical group 0.000 claims description 68
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 229910052731 fluorine Inorganic materials 0.000 claims description 35
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 22
- 239000011737 fluorine Substances 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 20
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000001624 naphthyl group Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 7
- JEMZBZYBGXMZBG-UHFFFAOYSA-N 9-[4-[4-(2-phenylbutanoyl)piperazin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C1CN(CCCCC2(C(=O)NCC(F)(F)F)C3=CC=CC=C3C3=CC=CC=C32)CCN1C(=O)C(CC)C1=CC=CC=C1 JEMZBZYBGXMZBG-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- BDTAPNUWYMHQBH-UHFFFAOYSA-N n-(2,2,2-trifluoroethyl)-9-[4-[4-[2-[4-(trifluoromethyl)phenyl]acetyl]piperazin-1-yl]butyl]fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)CC1=CC=C(C(F)(F)F)C=C1 BDTAPNUWYMHQBH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
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- 125000004076 pyridyl group Chemical group 0.000 claims description 6
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 4
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- 125000006168 tricyclic group Chemical group 0.000 claims description 4
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- 238000001727 in vivo Methods 0.000 claims description 3
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- ZUQAVVMTASPYSF-UHFFFAOYSA-N 9-[4-[4-[2-(2,4-dichlorophenyl)acetyl]piperazin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)CC1=CC=C(Cl)C=C1Cl ZUQAVVMTASPYSF-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
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- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
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- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- DXILZMMSZQFAIY-UHFFFAOYSA-N n-(2,2,2-trifluoroethyl)-9h-fluorene-9-carboxamide Chemical compound C1=CC=C2C(C(=O)NCC(F)(F)F)C3=CC=CC=C3C2=C1 DXILZMMSZQFAIY-UHFFFAOYSA-N 0.000 claims 3
- IKRPJHRYHOJOKW-UHFFFAOYSA-N 9-[4-[4-(benzylcarbamoyl)piperazin-1-yl]butyl]fluorene-9-carboxylic acid Chemical compound C(C1=CC=CC=C1)NC(=O)N1CCN(CC1)CCCCC1(C2=CC=CC=C2C=2C=CC=CC1=2)C(=O)O IKRPJHRYHOJOKW-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 1
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- STTRTQLSYQCQSG-UHFFFAOYSA-N n-cyclohexyl-9-[4-[4-(2-phenylacetyl)piperazin-1-yl]butyl]fluorene-9-carboxamide Chemical compound C1CN(CCCCC2(C(=O)NC3CCCCC3)C3=CC=CC=C3C3=CC=CC=C32)CCN1C(=O)CC1=CC=CC=C1 STTRTQLSYQCQSG-UHFFFAOYSA-N 0.000 description 1
- CXKOCSATJCQATQ-UHFFFAOYSA-N n-cyclopentyl-9-[4-[4-(2-phenylacetyl)piperazin-1-yl]butyl]fluorene-9-carboxamide Chemical compound C1CN(CCCCC2(C(=O)NC3CCCC3)C3=CC=CC=C3C3=CC=CC=C32)CCN1C(=O)CC1=CC=CC=C1 CXKOCSATJCQATQ-UHFFFAOYSA-N 0.000 description 1
- LFZLRDFWXBSLNX-UHFFFAOYSA-N n-ethyl-9-[4-[4-(2-phenylacetyl)piperazin-1-yl]butyl]fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC)CCCCN(CC1)CCN1C(=O)CC1=CC=CC=C1 LFZLRDFWXBSLNX-UHFFFAOYSA-N 0.000 description 1
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- CPGWSLFYXMRNDV-UHFFFAOYSA-N n-methyl-n-phenylcarbamoyl chloride Chemical compound ClC(=O)N(C)C1=CC=CC=C1 CPGWSLFYXMRNDV-UHFFFAOYSA-N 0.000 description 1
- YXDAXAOFHQQKQE-UHFFFAOYSA-N n-phenyl-4-[4-[9-(2,2,2-trifluoroethylcarbamoyl)fluoren-9-yl]butyl]piperazine-1-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)NC1=CC=CC=C1 YXDAXAOFHQQKQE-UHFFFAOYSA-N 0.000 description 1
- FBZOGGMULATMNA-UHFFFAOYSA-N n-phenyl-9-[4-[4-(2-phenylacetyl)piperazin-1-yl]butyl]fluorene-9-carboxamide Chemical compound C1CN(CCCCC2(C(=O)NC=3C=CC=CC=3)C3=CC=CC=C3C3=CC=CC=C32)CCN1C(=O)CC1=CC=CC=C1 FBZOGGMULATMNA-UHFFFAOYSA-N 0.000 description 1
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- JKNKNWJNCOJPLI-UHFFFAOYSA-N o-phthalaldehydic acid Chemical compound C1=CC=C2C(O)OC(=O)C2=C1 JKNKNWJNCOJPLI-UHFFFAOYSA-N 0.000 description 1
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- OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
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- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 108010088324 squalene cyclase Proteins 0.000 description 1
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- 239000007858 starting material Substances 0.000 description 1
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- 239000011550 stock solution Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- XNNITGPIBICDDF-UHFFFAOYSA-N tert-butyl 4-[4-[9-(2,2,2-trifluoroethylcarbamoyl)fluoren-9-yl]butyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CCCCC1(C(=O)NCC(F)(F)F)C2=CC=CC=C2C2=CC=CC=C21 XNNITGPIBICDDF-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by 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
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- 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
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- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
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- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
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- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
- C07D311/84—Xanthenes 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 in position 9
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- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07C2601/14—The ring being saturated
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- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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DE19963235A DE19963235A1 (de) | 1999-12-27 | 1999-12-27 | Substituierte Piperazinderivate, ihre Herstellung und ihre Verwendung als Arzneimittel |
Publications (1)
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ZA200205012B true ZA200205012B (en) | 2003-01-16 |
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ZA200205012A ZA200205012B (en) | 1999-12-27 | 2002-06-21 | Substituted piperazine derivatives as MTP inhibitors. |
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EP (1) | EP1259492A1 (xx) |
JP (1) | JP2003519131A (xx) |
KR (1) | KR20020065916A (xx) |
CN (1) | CN1414956A (xx) |
AR (1) | AR027112A1 (xx) |
AU (1) | AU2366001A (xx) |
BG (1) | BG106847A (xx) |
BR (1) | BR0016780A (xx) |
CA (1) | CA2394644A1 (xx) |
CO (1) | CO5251384A1 (xx) |
CZ (1) | CZ20022281A3 (xx) |
DE (1) | DE19963235A1 (xx) |
EA (1) | EA200200650A1 (xx) |
EE (1) | EE200200364A (xx) |
HU (1) | HUP0203855A3 (xx) |
IL (1) | IL150357A0 (xx) |
MX (1) | MXPA02006510A (xx) |
NO (1) | NO20023001D0 (xx) |
PL (1) | PL355394A1 (xx) |
SK (1) | SK9272002A3 (xx) |
TR (1) | TR200201669T2 (xx) |
UY (1) | UY26501A1 (xx) |
WO (1) | WO2001047899A1 (xx) |
YU (1) | YU49902A (xx) |
ZA (1) | ZA200205012B (xx) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
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BR0210616A (pt) | 2001-06-28 | 2004-09-28 | Pfizer Prod Inc | Indóis, benzofuranos e benzotiofenos substituìdos com triamida, composição farmacêutica, uso dos referidos compostos, bem como processo para preparação dos mesmos |
DE10200633A1 (de) * | 2002-01-10 | 2003-07-24 | Boehringer Ingelheim Pharma | Kombination von MTP Inhibitoren oder apoB-Sekretions-Inhibitoren mit Fibraten zur Verwendung als Arzneimittel |
KR100717098B1 (ko) | 2002-02-28 | 2007-05-10 | 니뽄 다바코 산교 가부시키가이샤 | 에스테르 화합물 및 그 의약 용도 |
JP4832897B2 (ja) * | 2003-08-29 | 2011-12-07 | 日本たばこ産業株式会社 | エステル誘導体及びその医薬用途 |
US20060030623A1 (en) * | 2004-07-16 | 2006-02-09 | Noboru Furukawa | Agent for the treatment or prevention of diabetes, obesity or arteriosclerosis |
US8101774B2 (en) | 2004-10-18 | 2012-01-24 | Japan Tobacco Inc. | Ester derivatives and medicinal use thereof |
MX2007004973A (es) * | 2004-10-25 | 2007-06-14 | Japan Tobacco Inc | Formulacion solida con solubilidad y estabilidad mejoradas y metodo para producir la formulacion. |
JO2653B1 (en) | 2006-10-24 | 2012-06-17 | شركة جانسين فارماسوتيكا ان. في | Tetrahydroflavin 1-carboxylic acid substituted with pyridine or pyrazine inhibit MTB |
EA017376B1 (ru) * | 2006-10-24 | 2012-12-28 | Янссен Фармацевтика Нв | Производные тетрагидронафталин-1-карбоновой кислоты, ингибирующие мтр |
US8190707B2 (en) | 2007-10-20 | 2012-05-29 | Citrix Systems, Inc. | System and method for transferring data among computing environments |
CA2710039C (en) | 2007-12-26 | 2018-07-03 | Critical Outcome Technologies, Inc. | Semicarbazones, thiosemicarbazones and related compounds and methods for treatment of cancer |
CA2730890C (en) | 2008-07-17 | 2018-05-15 | Critical Outcome Technologies Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
CA2794952C (en) | 2010-04-01 | 2018-05-15 | Critical Outcome Technologies Inc. | Compounds and method for treatment of hiv |
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US5739135A (en) * | 1993-09-03 | 1998-04-14 | Bristol-Myers Squibb Company | Inhibitors of microsomal triglyceride transfer protein and method |
US5885983A (en) * | 1996-05-10 | 1999-03-23 | Bristol-Myers Squibb Company | Inhibitors of microsomal triglyceride transfer protein and method |
WO1998027979A1 (en) * | 1996-12-20 | 1998-07-02 | Bristol-Myers Squibb Company | Heterocyclic inhibitors of microsomal triglyceride transfer protein and method |
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1999
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2000
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BG106847A (en) | 2003-02-28 |
NO20023001L (no) | 2002-06-21 |
WO2001047899A1 (de) | 2001-07-05 |
AU2366001A (en) | 2001-07-09 |
UY26501A1 (es) | 2001-07-31 |
CN1414956A (zh) | 2003-04-30 |
JP2003519131A (ja) | 2003-06-17 |
HUP0203855A2 (hu) | 2003-03-28 |
HUP0203855A3 (en) | 2004-07-28 |
EA200200650A1 (ru) | 2002-12-26 |
DE19963235A1 (de) | 2001-07-05 |
AR027112A1 (es) | 2003-03-12 |
NO20023001D0 (no) | 2002-06-21 |
EE200200364A (et) | 2003-10-15 |
MXPA02006510A (es) | 2002-11-29 |
EP1259492A1 (de) | 2002-11-27 |
CA2394644A1 (en) | 2001-07-05 |
US20030114442A1 (en) | 2003-06-19 |
PL355394A1 (en) | 2004-04-19 |
IL150357A0 (en) | 2002-12-01 |
YU49902A (sh) | 2005-03-15 |
TR200201669T2 (tr) | 2002-10-21 |
CZ20022281A3 (cs) | 2002-10-16 |
KR20020065916A (ko) | 2002-08-14 |
SK9272002A3 (en) | 2002-11-06 |
BR0016780A (pt) | 2002-08-27 |
CO5251384A1 (es) | 2003-02-28 |
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