CA2441080A1 - Composes d'aryl alkylamines non imidazole comme antagonistes des recepteurs h3 de l'histamine, preparation et applications therapeutiques - Google Patents
Composes d'aryl alkylamines non imidazole comme antagonistes des recepteurs h3 de l'histamine, preparation et applications therapeutiques Download PDFInfo
- Publication number
- CA2441080A1 CA2441080A1 CA002441080A CA2441080A CA2441080A1 CA 2441080 A1 CA2441080 A1 CA 2441080A1 CA 002441080 A CA002441080 A CA 002441080A CA 2441080 A CA2441080 A CA 2441080A CA 2441080 A1 CA2441080 A1 CA 2441080A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- chr5
- mmol
- piperidin
- histamine
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 229940115480 Histamine H3 receptor antagonist Drugs 0.000 title abstract description 11
- 239000003395 histamine H3 receptor antagonist Substances 0.000 title abstract description 11
- 238000002360 preparation method Methods 0.000 title description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title description 12
- 230000001225 therapeutic effect Effects 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 238000000034 method Methods 0.000 claims abstract description 104
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- 108090000981 Histamine H3 receptors Proteins 0.000 claims abstract description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 208000008589 Obesity Diseases 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 8
- 235000020824 obesity Nutrition 0.000 claims abstract description 8
- -1 CH2 aryl Chemical group 0.000 claims description 63
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 55
- 239000005557 antagonist Substances 0.000 claims description 30
- 229960001340 histamine Drugs 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 230000027455 binding Effects 0.000 claims description 21
- 150000002431 hydrogen Chemical group 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 230000002265 prevention Effects 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 230000009286 beneficial effect Effects 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 101100496169 Arabidopsis thaliana CLH1 gene Proteins 0.000 claims description 2
- 101100044057 Mesocricetus auratus SYCP3 gene Proteins 0.000 claims description 2
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- 101100080600 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nse6 gene Proteins 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 101150111293 cor-1 gene Proteins 0.000 claims description 2
- 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 claims 32
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 8
- 239000012453 solvate Substances 0.000 claims 7
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 43
- 230000000694 effects Effects 0.000 abstract description 7
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 53
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 52
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- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 18
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 15
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- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
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- 238000001914 filtration Methods 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
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- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 8
- 239000012131 assay buffer Substances 0.000 description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-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 7
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- 101710093886 Histamine H4 receptor Proteins 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
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- 238000010626 work up procedure Methods 0.000 description 7
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 238000007790 scraping Methods 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
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- 230000009870 specific binding Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
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- 239000012058 sterile packaged powder Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
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- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- JZRHUCWLYPNRAO-UHFFFAOYSA-N tert-butyl 6-(2-piperidin-1-ylethoxy)-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C=1C=C2CN(C(=O)OC(C)(C)C)CCC2=CC=1OCCN1CCCCC1 JZRHUCWLYPNRAO-UHFFFAOYSA-N 0.000 description 1
- RMTMPEWYYUABFV-UHFFFAOYSA-N tert-butyl 6-(3-piperidin-1-ylpropoxy)-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C=1C=C2CN(C(=O)OC(C)(C)C)CCC2=CC=1OCCCN1CCCCC1 RMTMPEWYYUABFV-UHFFFAOYSA-N 0.000 description 1
- QOYNVCNQZQNXNA-UHFFFAOYSA-N tert-butyl 6-[3-(2-methylpiperidin-1-yl)propoxy]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound CC1CCCCN1CCCOC1=CC=C(CN(CC2)C(=O)OC(C)(C)C)C2=C1 QOYNVCNQZQNXNA-UHFFFAOYSA-N 0.000 description 1
- JHUFJJBVXLSYPP-UHFFFAOYSA-N tert-butyl 6-[3-(dimethylamino)propoxy]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=CC(OCCCN(C)C)=CC=C21 JHUFJJBVXLSYPP-UHFFFAOYSA-N 0.000 description 1
- IVHHZZKGSYGTKZ-UHFFFAOYSA-N tert-butyl 6-hydroxy-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound OC1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 IVHHZZKGSYGTKZ-UHFFFAOYSA-N 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- BSXLLFUSNQCWJP-UHFFFAOYSA-N thiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CS1 BSXLLFUSNQCWJP-UHFFFAOYSA-N 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- 229950011533 tiotidine Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000012043 vestibular reflex Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
- C07C217/18—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
- C07C217/20—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/58—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/68—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/73—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/08—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by oxygen atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
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- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- C07C271/32—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/09—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton the carbon skeleton being further substituted by at least two halogen atoms
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/11—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C311/18—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07D207/14—Nitrogen atoms not forming part of a nitro radical
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- 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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- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Furan Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Pyrrole Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
L'invention concerne de nouveaux composés d'aryl alkylamine substitués représentés par la formule (I), ou des sels pharmaceutiquement acceptables de ceux-ci, qui possèdent une activité sélective d'antagoniste des récepteurs H3 de l'histamine, ainsi que des procédés de préparation de ces composés. Dans une autre forme de réalisation, l'invention concerne des compositions pharmaceutiques contenant de telles amines cycliques, ainsi que des procédés d'utilisation de celles-ci pour traiter l'obésité et d'autres maladies associées aux récepteurs H3 de l'histamine.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27823001P | 2001-03-23 | 2001-03-23 | |
| US60/278,230 | 2001-03-23 | ||
| PCT/US2002/006644 WO2002076925A2 (fr) | 2001-03-23 | 2002-03-21 | Composes d'aryl alkylamines non imidazole comme antagonistes des recepteurs h3 de l'histamine, preparation et applications therapeutiques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2441080A1 true CA2441080A1 (fr) | 2002-10-03 |
Family
ID=23064195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002441080A Abandoned CA2441080A1 (fr) | 2001-03-23 | 2002-03-21 | Composes d'aryl alkylamines non imidazole comme antagonistes des recepteurs h3 de l'histamine, preparation et applications therapeutiques |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1379493A2 (fr) |
| JP (1) | JP2004532834A (fr) |
| AU (1) | AU2002254114A1 (fr) |
| CA (1) | CA2441080A1 (fr) |
| WO (1) | WO2002076925A2 (fr) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002357775A1 (en) | 2001-12-10 | 2003-06-23 | Ortho-Mcneil Pharmaceutical, Inc. | Phenylalkynes |
| US20040002604A1 (en) | 2001-12-10 | 2004-01-01 | Richard Apodaca | Phenylalkynes |
| DE10235312A1 (de) | 2002-08-01 | 2004-02-12 | Basf Ag | Verfahren zur Herstellung von Aminoalkoxybenzylaminen und Aminoalkoxybenzonitrilen als Zwischenprodukte |
| GB0224083D0 (en) * | 2002-10-16 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| GB0224084D0 (en) | 2002-10-16 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| AU2003274053A1 (en) * | 2002-10-22 | 2004-05-13 | Glaxo Group Limited | Aryloxyalkylamine derivates as h3 receptor ligands |
| GB0224557D0 (en) | 2002-10-22 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| PT1558595E (pt) | 2002-10-23 | 2010-01-15 | Janssen Pharmaceutica Nv | Piperazinil e diazepanil benzamidas e benzotioamidas |
| CA2504272A1 (fr) | 2002-10-23 | 2004-05-06 | Janssen Pharmaceutica, N.V. | Phenylpiperidines et phenylpyrrolidines utilisees comme modulateurs du recepteur h3 de l'histamine |
| ATE402165T1 (de) | 2003-04-23 | 2008-08-15 | Glaxo Group Ltd | Piperazin derivate und ihre verwendung für die behandlung von neurologischen und psychiatrischen krankheiten. |
| DE10325258B4 (de) | 2003-06-03 | 2008-08-21 | Diehl Aerospace Gmbh | Luftfahrzeugkabinengerätesteuerung |
| JP4765627B2 (ja) | 2003-09-22 | 2011-09-07 | Msd株式会社 | 新規ピペリジン誘導体 |
| EP1720861A2 (fr) | 2004-02-25 | 2006-11-15 | Eli Lilly And Company | Antagonistes du recepteur d'histamine h3, leur preparation et leurs utilisations therapeutiques |
| CN1960969B (zh) | 2004-04-01 | 2012-03-28 | 伊莱利利公司 | 组胺h3受体药物、其制备方法及治疗用途 |
| JP2007532638A (ja) * | 2004-04-14 | 2007-11-15 | アストラゼネカ・アクチエボラーグ | Nk1アンタゴニスト及びセロトニン再取り込み阻害剤としてのアリールグリシンアミド誘導体及びその使用 |
| US7456164B2 (en) | 2004-05-07 | 2008-11-25 | Pfizer, Inc | 3- or 4-monosubtituted phenol and thiophenol derivatives useful as H3 ligands |
| AU2005243153A1 (en) | 2004-05-07 | 2005-11-24 | Janssen Pharmaceutica N.V. | Scalable synthesis of imidazole derivatives |
| CA2565852C (fr) * | 2004-05-07 | 2010-08-10 | Warner-Lambert Company Llc | Derives de phenol et de thiophenol 3- ou 4-monosubstitues utiles en tant que ligands h3 |
| EP1593679A1 (fr) * | 2004-05-07 | 2005-11-09 | Warner-Lambert Company LLC | Dérivés de phénol 3- ou 4-monosubstitués utiles comme ligands de H3 |
| US7205316B2 (en) | 2004-05-12 | 2007-04-17 | Abbott Laboratories | Tri- and bi-cyclic heteroaryl histamine-3 receptor ligands |
| EP1595881A1 (fr) | 2004-05-12 | 2005-11-16 | Pfizer Limited | Dérivés de tetrahydronaphthyridine en tant que ligands de récepteur H3 d'histamine |
| US20050256309A1 (en) * | 2004-05-12 | 2005-11-17 | Altenbach Robert J | Tri-and bi-cyclic heteroaryl histamine-3 receptor ligands |
| FR2870846B1 (fr) * | 2004-05-25 | 2006-08-04 | Sanofi Synthelabo | Derives de tetrahydroisoquinolylsulfonamides, leur preparation et leur utilisation en therapeutique |
| DK1755593T3 (da) * | 2004-06-02 | 2008-05-19 | Hoffmann La Roche | Naphtalenderivater der er nyttige som histamin-3-receptorligander |
| US7696234B2 (en) | 2004-06-02 | 2010-04-13 | Eli Lilly And Company | Histamine H3 receptor agents, preparation and therapeutic uses |
| US20060014733A1 (en) * | 2004-07-19 | 2006-01-19 | Pfizer Inc | Histamine-3 agonists and antagonists |
| ES2325865T3 (es) | 2004-07-26 | 2009-09-22 | Eli Lilly And Company | Derivados de oxazol como agentes receptores de histamina h3, preparacion y usos terapeuticos. |
| JP4942654B2 (ja) * | 2004-08-23 | 2012-05-30 | イーライ リリー アンド カンパニー | ヒスタミンh3受容体薬剤、製剤及び治療的使用 |
| US7846950B2 (en) | 2004-10-18 | 2010-12-07 | Eli Lilly And Company | Histamine H3 receptor inhibitors, preparation and therapeutic uses |
| MX2007004465A (es) * | 2004-10-19 | 2007-05-07 | Hoffmann La Roche | Derivados de quinolina. |
| CN101142180B (zh) | 2005-03-17 | 2011-05-04 | 伊莱利利公司 | 作为组胺h3受体拮抗剂的吡咯烷衍生物 |
| EP1707204A1 (fr) * | 2005-04-01 | 2006-10-04 | Bioprojet | Utilization des allkylamines sans imidazoles comme ligandes du recepteur histamine H3 pour le traitement de l'epilepsie |
| CA2602234C (fr) * | 2005-04-01 | 2014-01-14 | Eli Lilly And Company | Agents agissant sur le recepteur h3 de l'histamine, leur preparation et leurs utilisations therapeutiques |
| EP1717235A3 (fr) * | 2005-04-29 | 2007-02-28 | Bioprojet | Phenoxypropylpiperidines and -pyrrolidines et leur utilisation comme ligands du récepteur histaminique H3 |
| EP1717233A1 (fr) * | 2005-04-29 | 2006-11-02 | Bioprojet | Ligands du récepteur histaminique H3 et leur application thérapeutique |
| WO2007005503A1 (fr) | 2005-07-01 | 2007-01-11 | Eli Lilly And Company | Agents recepteurs de l'histamine h3, preparation et utilisations therapeutiques |
| ME01181B (fr) | 2005-09-16 | 2013-03-20 | Janssen Pharmaceutica Nv | Cyclopropylamines en tant que modulateurs du récepteur de l'histamine h3 |
| US8158673B2 (en) | 2005-10-27 | 2012-04-17 | Pfizer Inc. | Histamine-3 receptor antagonists |
| WO2007052124A1 (fr) * | 2005-11-04 | 2007-05-10 | Pfizer Limited | Dérivé de tétrahydronaphtyridine |
| EP1790646A1 (fr) | 2005-11-24 | 2007-05-30 | Sanofi-Aventis | Derives de Isoquinoline et Benzo[h]Isoquinoline, leur preparation et leur utilisation en thérapeutique en tant qu'antagonistes du recepteur de l'histamine H3. |
| WO2007069053A1 (fr) * | 2005-12-14 | 2007-06-21 | Pfizer Products Inc. | Antagonistes benzimidazoliques du récepteur h-3 |
| WO2007099423A1 (fr) * | 2006-03-02 | 2007-09-07 | Pfizer Products Inc. | Dérivés de 1-pyrrolidine indane en tant qu'antagonistes du récepteur d'histamine 3 |
| US20080186971A1 (en) * | 2007-02-02 | 2008-08-07 | Tarari, Inc. | Systems and methods for processing access control lists (acls) in network switches using regular expression matching logic |
| WO2008109336A1 (fr) | 2007-03-01 | 2008-09-12 | Janssen Pharmaceutica N.V. | Composés de tétrahydroisoquinoline en tant que modulateurs du récepteur histamine h3 |
| EA201000316A1 (ru) | 2007-09-12 | 2010-10-29 | ВАЙЕТ ЭлЭлСи | Производные изохинолинила и изоиндолинила в качестве антагонистов гистаминовых рецепторов 3 подтипа |
| WO2010026113A1 (fr) * | 2008-09-03 | 2010-03-11 | Evotec Neurosciences Gmbh | Acyl- et sufonyl-tétrahydronaphtyridines et dérivés aza de celles-ci en tant qu’antagonistes de récepteur d’histamine h3 |
| WO2010052222A1 (fr) * | 2008-11-07 | 2010-05-14 | Evotec Neurosciences Gmbh | Dérivés (dihydro)naphthyridinone comme antagonistes du récepteur h3 de l’histamine |
| AR080375A1 (es) | 2010-03-05 | 2012-04-04 | Sanofi Aventis | Procedimiento para la preparacion de 2-(cicloheximetil)-n-{2-[(2s)-1-metilpirrolidin-2-il] etil}-1,2,3,4-tetrahidroisoquinolina- 7-sulfonamida |
| US9079888B2 (en) * | 2011-02-23 | 2015-07-14 | Suven Life Sciences Limited | Compounds as histamine H3 receptor ligands |
| WO2013151982A1 (fr) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Méthodes et composés utiles pour traiter le prurit, et procédés d'identification desdits composés |
| EP2647377A1 (fr) | 2012-04-06 | 2013-10-09 | Sanofi | Utilisation d'un antagoniste du récepteur h3 pour le traitement de la maladie d'Alzheimer |
| EP2745876A1 (fr) * | 2012-12-21 | 2014-06-25 | Prous Institute for Biomedical Research, S.A. | Dérivés d'éther d'aminoalkyle de phenyle substitués par substituents hydroxy aliphatique |
| WO2015112806A2 (fr) | 2014-01-24 | 2015-07-30 | Tp Therapeutics, Inc. | Macrocycles de diaryle en tant que modulateurs de protéines kinases |
| ES2864839T3 (es) | 2015-07-02 | 2021-10-14 | Turning Point Therapeutics Inc | Macrociclos de diarilo quirales como moduladores de proteína quinasas |
| ES2979111T3 (es) | 2015-07-06 | 2024-09-24 | Turning Point Therapeutics Inc | Polimorfo de macrociclo de diarilo |
| CN106995410B (zh) * | 2016-01-26 | 2021-03-02 | 江苏恩华药业股份有限公司 | 一种内酰胺类衍生物及其应用 |
| US10730830B2 (en) * | 2016-01-29 | 2020-08-04 | Ono Pharmaceutical Co., Ltd. | Tetrahydronaphthalene derivative |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2810719A (en) * | 1954-10-19 | 1957-10-22 | Abbott Lab | Morpholino alkyl ethers of hydroxybenzoic acid esters |
| HU187208B (en) * | 1982-12-28 | 1985-11-28 | Richter Gedeon Vegyeszet | Process for production of new dialcil-amino-alcoxi-benzoalcohole derivates, their acid additional and quaterner soils and medical preparates consisting of them |
| US5585492A (en) * | 1994-10-11 | 1996-12-17 | G. D. Searle & Co. | LTA4 Hydrolase inhibitors |
| ATE355264T1 (de) * | 1997-10-15 | 2006-03-15 | Wyeth Corp | Neue aryloxy-alkyl-dialkylamine |
| EP0982300A3 (fr) * | 1998-07-29 | 2000-03-08 | Societe Civile Bioprojet | Non-imidazole alkylamines comme antagonistes du recepteur histamine H3 et leur application thérapeutique |
| KR100852362B1 (ko) * | 2000-08-08 | 2008-08-14 | 오르토-맥네일 파마슈티칼, 인코퍼레이티드 | 비-이미다졸 아릴옥시피페리딘 |
| KR100846339B1 (ko) * | 2000-11-20 | 2008-07-15 | 바이오비트럼 에이비(피유비엘) | 세로토닌 5ht-2 수용체의 아고니스트 또는안타고니스트로서의 피페라지닐피라진 화합물 |
-
2002
- 2002-03-21 WO PCT/US2002/006644 patent/WO2002076925A2/fr not_active Ceased
- 2002-03-21 CA CA002441080A patent/CA2441080A1/fr not_active Abandoned
- 2002-03-21 JP JP2002576188A patent/JP2004532834A/ja not_active Withdrawn
- 2002-03-21 EP EP02723329A patent/EP1379493A2/fr not_active Withdrawn
- 2002-03-21 AU AU2002254114A patent/AU2002254114A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002076925A3 (fr) | 2003-09-18 |
| AU2002254114A1 (en) | 2002-10-08 |
| WO2002076925A2 (fr) | 2002-10-03 |
| EP1379493A2 (fr) | 2004-01-14 |
| JP2004532834A (ja) | 2004-10-28 |
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