JP5143558B2 - ヘッジホッグシグナル伝達のピリジルインヒビター - Google Patents
ヘッジホッグシグナル伝達のピリジルインヒビター Download PDFInfo
- Publication number
- JP5143558B2 JP5143558B2 JP2007530390A JP2007530390A JP5143558B2 JP 5143558 B2 JP5143558 B2 JP 5143558B2 JP 2007530390 A JP2007530390 A JP 2007530390A JP 2007530390 A JP2007530390 A JP 2007530390A JP 5143558 B2 JP5143558 B2 JP 5143558B2
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- alkyl
- pyridin
- phenyl
- heterocycle
- 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.)
- Expired - Lifetime
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- 0 C*1=NC(c2cc([*+2])ccc2Cl)=CC1 Chemical compound C*1=NC(c2cc([*+2])ccc2Cl)=CC1 0.000 description 18
- XRDAOUSTUIGOSY-IMOMWIHDSA-N C/C=C\C=C/C([C@@H](C1)NC=C1NC(C1=CCC(CNCC2OCCC2)CC1)=O)=C Chemical compound C/C=C\C=C/C([C@@H](C1)NC=C1NC(C1=CCC(CNCC2OCCC2)CC1)=O)=C XRDAOUSTUIGOSY-IMOMWIHDSA-N 0.000 description 1
- KWLBFEZSHQMNEK-UHFFFAOYSA-N CC(C1)NC(C)CN1c(cc1)ncc1C(Nc(cc1)cc(-c2ncccc2)c1Cl)=O Chemical compound CC(C1)NC(C)CN1c(cc1)ncc1C(Nc(cc1)cc(-c2ncccc2)c1Cl)=O KWLBFEZSHQMNEK-UHFFFAOYSA-N 0.000 description 1
- ZZTNADBLUGPGRF-UHFFFAOYSA-N CCOc1cc(C(Nc(cc2)cc(-c3ncccc3)c2Cl)=O)ccc1CS(C)(=O)=O Chemical compound CCOc1cc(C(Nc(cc2)cc(-c3ncccc3)c2Cl)=O)ccc1CS(C)(=O)=O ZZTNADBLUGPGRF-UHFFFAOYSA-N 0.000 description 1
- WEHFAGNOWLYNSI-UHFFFAOYSA-N CS(c1ccc(C(Nc(cc2)cc(-c3ccccn3)c2Cl)=O)[s]1)(=O)=O Chemical compound CS(c1ccc(C(Nc(cc2)cc(-c3ccccn3)c2Cl)=O)[s]1)(=O)=O WEHFAGNOWLYNSI-UHFFFAOYSA-N 0.000 description 1
- IPACATJLCJFHRS-UHFFFAOYSA-N C[N+](C)(c(cc1I)ccc1[ClH+])[O-] Chemical compound C[N+](C)(c(cc1I)ccc1[ClH+])[O-] IPACATJLCJFHRS-UHFFFAOYSA-N 0.000 description 1
- GEEGVMIQHGOMES-UHFFFAOYSA-N C[n]1c(S(Cc(cc2)ccc2C(Nc(cc2)cc(-c3ncccc3)c2Cl)=O)(=O)=O)nnc1 Chemical compound C[n]1c(S(Cc(cc2)ccc2C(Nc(cc2)cc(-c3ncccc3)c2Cl)=O)(=O)=O)nnc1 GEEGVMIQHGOMES-UHFFFAOYSA-N 0.000 description 1
- OVBHFSVVLGFDRH-UHFFFAOYSA-N C[n]1c(S(Cc(cc2)ccc2C(Nc(cc2)cc(-c3ncccc3)c2Cl)=O)=O)nnc1 Chemical compound C[n]1c(S(Cc(cc2)ccc2C(Nc(cc2)cc(-c3ncccc3)c2Cl)=O)=O)nnc1 OVBHFSVVLGFDRH-UHFFFAOYSA-N 0.000 description 1
- HYZSWKVNMKNZCL-UHFFFAOYSA-N Nc(cc1)cc(C2=CC=C[I]=N2)c1Cl Chemical compound Nc(cc1)cc(C2=CC=C[I]=N2)c1Cl HYZSWKVNMKNZCL-UHFFFAOYSA-N 0.000 description 1
- QBMVQQABRBAZQB-UHFFFAOYSA-N O=C(c(cc1)ccc1S(N1CCOCC1)(=O)=O)NC(C=C1c2ccccn2)=CCC1Cl Chemical compound O=C(c(cc1)ccc1S(N1CCOCC1)(=O)=O)NC(C=C1c2ccccn2)=CCC1Cl QBMVQQABRBAZQB-UHFFFAOYSA-N 0.000 description 1
- DBQKBBCUHQDTGT-UHFFFAOYSA-N O=C(c(ccc(Cl)n1)c1Cl)Nc(cc1-c2ncccc2)ccc1Cl Chemical compound O=C(c(ccc(Cl)n1)c1Cl)Nc(cc1-c2ncccc2)ccc1Cl DBQKBBCUHQDTGT-UHFFFAOYSA-N 0.000 description 1
- KVZHDUPKKMGIPA-UHFFFAOYSA-N O=C(c1ccc(CC2CCNCC2)cc1)Nc(cc1)cc(-c2ccccn2)c1Cl Chemical compound O=C(c1ccc(CC2CCNCC2)cc1)Nc(cc1)cc(-c2ccccn2)c1Cl KVZHDUPKKMGIPA-UHFFFAOYSA-N 0.000 description 1
- MPEPYTIRGWQYRH-UHFFFAOYSA-O [NH3+]S(c(cc1)ccc1C(Nc(cc1-c2ncccc2)ccc1Cl)=O)(=O)=O Chemical compound [NH3+]S(c(cc1)ccc1C(Nc(cc1-c2ncccc2)ccc1Cl)=O)(=O)=O MPEPYTIRGWQYRH-UHFFFAOYSA-O 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/06—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07D213/02—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
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- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
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- C07D213/54—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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- C07D213/02—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
- 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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
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- C07D213/02—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
- 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
- C07D213/60—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 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/60—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 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
- C07D213/78—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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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/60—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 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
- C07D213/78—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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- C07D213/82—Amides; Imides in position 3
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- 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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- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/141—Esters of phosphorous acids
- C07F9/142—Esters of phosphorous acids with hydroxyalkyl compounds without further substituents on alkyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
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