JP4627987B2 - 低分子侵入阻害剤 - Google Patents
低分子侵入阻害剤 Download PDFInfo
- Publication number
- JP4627987B2 JP4627987B2 JP2003574182A JP2003574182A JP4627987B2 JP 4627987 B2 JP4627987 B2 JP 4627987B2 JP 2003574182 A JP2003574182 A JP 2003574182A JP 2003574182 A JP2003574182 A JP 2003574182A JP 4627987 B2 JP4627987 B2 JP 4627987B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- compounds
- alkanediyl
- amino
- acid
- 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 - Fee Related
Links
Classifications
-
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
- C07C229/58—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/53—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/55—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C233/81—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 carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/56—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C237/42—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 nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—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 a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/46—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/14—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/72—4,7-Endo-alkylene-iso-indoles
- C07D209/76—4,7-Endo-alkylene-iso-indoles with oxygen atoms in positions 1 and 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—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
- 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
-
- 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
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Description
本発明の化合物はHIVウイルスが宿主細胞に侵入する過程を阻害する阻害剤であることを見いだした。前記化合物は式(I)
Aは、アリール、ヘテロアリールまたはヘテロシクロアルキルであり、
R1は、水素、ハロゲン、ヒドロキシ、アミノ、ニトロ、アルキル、アルキルオキシまたは式(II)
R2は、アルキル、アルケニル、アルキニル、ヒドロキシ、ハロゲン、ニトロ、シアノ、アミノ、ハロアルキル、シクロアルキル、アリール、ヘテロアリール、ヘテロシクロアルキル、R8−O−、R8−S−、R8−S(=O)2−、R8−C(=O)−、R8−C(=S)−、R8−C(=NH)−、R8−C(=NCN)−、R8−NH−、(R8)2−N−、HO−C(=O)−、NH2−C(=O)−、NH2−S(=O)2−、NH2−C(=S)−、NH2−C(=NH)−、NH2−C(=NCN)−、R8−NR4−C(=O)−、R8−NR4−S(=O)2−、R8−O−C(=O)−、R8−C(=O)−NR4−、R8−S(=O)2−NR4−、R8−C(=O)−O−、R8−S−CH2−またはR8−O−CH2−C(=O)−を表し、
R3は、ヒドロキシ、アミノ、アルキルオキシ、シクロアルキルオキシまたは一置換もしくは二置換アミノ[ここで、置換基はアルキルおよびシクロアルキルから選択可能である]を表し、
R4は、水素、アルキルまたはシクロアルキルを表し、
R6は、水素、アミノ、R7−C(=O)−、R8−S(=O)2−NH−、R8−C(=O)−NH−、R8−C(=S)−NH−、R8−C(=NH)−NH−、R8−C(=NCN)−NH−、R8−O−C(=O)−NH−、R8−O−アルカンジイル−C(=O)−NH−、R8−アルカンジイル−S(=O)2−NH−、アリール−アルカンジイル−C(=O)−NH−、アリール−アルケンジイル−C(=O)−NH−、ヘテロアリール−アルカンジイル−C(=O)−NH−、シクロアルキル−アルカンジイル−C(=O)−NH−、ヘテロシクロアルキル−アルカンジイル−C(=O)−NH−または置換アルキル[ここで、置換基はアミノ、R7−C(=O)−、R8−S(=O)2−NH−、R8−C(=O)−NH−、R8−C(=S)−NH−、R8−C(=NH)−NH−、R8−C(=NCN)−NH−、R8−O−C(=O)−NH−、R8−O−アルカンジイル−C(=O)−NH−、R8−アルカンジイル−S(=O)2−NH−、アリール−アルカンジイル−C(=O)−NH−、ヘテロアリール−アルカンジイル−C(=O)−NH−、シクロアルキル−アルカンジイル−C(=O)−NH−およびヘテロシクロアルキル−アルカンジイル−C(=O)−NH−から選択可能である]であり、
R7は、ヒドロキシ、アミノ、アルキルオキシ、シクロアルキルオキシまたは一置換もしくは二置換アミノ[ここで、置換基はアルキルおよびシクロアルキルから選択可能である]を表し、
R8は、アルキル、ハロアルキル、シクロアルキル、アリール、ヘテロアリールまたはヘテロシクロアルキルを表し、
Yは、アルカンジイル、−C(=O)−、−C(=S)−、−C(=NH)−、−C(=NCN)−、−S(=O)−、−S(=O)2−、−C(=O)−CH2−O−、−C(=O)−O−、−C(=O)−(CH2)p−、−C(=O)−NH−またはアルケンジイル−C(=O)−を表し、
Xは、直接結合、−O−、−S−、−S(=O)2−、−O−S(=O)2−、−S(=O)2−O−、−NH−S(=O)2−、−S(=O)2−NH−、−C(=O)−、−C(=S)−、−C(=NH)−、−C(=NCN)−、−O−C(=O)−、−C(=O)−O−、−NH−C(=O)−、−C(=O)−NH−またはアルカンジイルであり、
mおよびnは、各々独立して、ゼロ、1または2であり、
pは、1から4の整数である}
で表される化合物、これらのN−オキサイド形態、立体化学異性体、ラセミ混合物、塩、プロドラッグ、エステルおよび代謝産物である。
R1は、水素、ハロゲンまたは式(II)
R2は、アルキル、アルケニル、アルキニル、ヒドロキシ、ハロゲン、ニトロ、シアノ、アミノ、ハロアルキル、シクロアルキル、アリール、ヘテロアリール、ヘテロシクロアルキル、R8−O−、R8−S−、R8−S(=O)2−、R8−C(=O)−、R8−C(=S)−、R8−C(=NH)−、R8−C(=NCN)−、R8−NH−、(R8)2−N−、HO−C(=O)−、NH2−C(=O)−、NH2−S(=O)2−、NH2−C(=S)−、NH2−C(=NH)−、NH2−C(=NCN)−、R8−NR4−C(=O)−、R8−NR4−S(=O)2−、R8−O−C(=O)−、R8−C(=O)−NR4−、R8−S(=O)2−NR4−またはR8−C(=O)−O−を表し、
R3は、ヒドロキシ、アミノ、アルキルオキシ、シクロアルキルオキシまたは一置換もしくは二置換アミノ[ここで、置換基はアルキルおよびシクロアルキルから選択可能である]を表し、
R4は、水素、アルキルまたはシクロアルキルを表し、
R6は、水素、アミノ、R7−C(=O)−、R8−S(=O)2−NH−、R8−C(=O)−NH−、R8−C(=S)−NH−、R8−C(=NH)−NH−、R8−C(=NCN)−NH−、R8−O−C(=O)−NH−、R8−O−アルカンジイル−C(=O)−NH−、R8−アルカンジイル−S(=O)2−NH−、アリール−アルカンジイル−C(=O)−NH−、ヘテロアリール−アルカンジイル−C(=O)−NH−、シクロアルキル−アルカンジイル−C(=O)−NH−、ヘテロシクロアルキル−アルカンジイル−C(=O)−NH−または置換アルキル[ここで、置換基はアミノ、R7−C(=O)−、R8−S(=O)2−NH−、R8−C(=O)−NH−、R8−C(=S)−NH−、R8−C(=NH)−NH−、R8−C(=NCN)−NH−、R8−O−C(=O)−NH−、R8−O−アルカンジイル−C(=O)−NH−、R8−アルカンジイル−S(=O)2−NH−、アリール−アルカンジイル−C(=O)−NH−、ヘテロアリール−アルカンジイル−C(=O)−NH−、シクロアルキル−アルカンジイル−C(=O)−NH−およびヘテロシクロアルキル−アルカンジイル−C(=O)−NH−から選択可能である]であり、
R7は、ヒドロキシ、アミノ、アルキルオキシ、シクロアルキルオキシまたは一置換もしくは二置換アミノ[ここで、置換基はアルキルおよびシクロアルキルから選択可能である]を表し、
R8は、アルキル、シクロアルキル、アリール、ヘテロアリールまたはヘテロシクロアルキルを表し、
Yは、アルカンジイル、−C(=O)−、−C(=S)−、−C(=NH)−、−C(=NCN)−、−S(=O)−、−S(=O)2−、−C(=O)−CH2−O−、−C(=O)−O−、−C(=O)−(CH2)p−を表し、
Xは、直接結合、−O−、−S−、−S(=O)2−、−O−S(=O)2−、−S(=O)2−O−、−NH−S(=O)2−、−S(=O)2−NH−、−C(=O)−、−C(=S)−、−C(=NH)−、−C(=NCN)−、−O−C(=O)−、−C(=O)−O−、−NH−C(=O)−、−C(=O)−NH−またはアルカンジイルであり、
mおよびnは、各々独立して、ゼロ、1または2であり、
pは、1から4の整数である}
で表される化合物、これらのN−オキサイド形態、立体化学異性体、ラセミ混合物、塩、プロドラッグ、エステルおよび代謝産物も包含する。
・ Yが−C(=O)−または−S(=O)2−であり、
・ R1が式(II)であり、
・ R2がハロゲン、ブロモ、クロロ、アルキル、ハロアルキル、アルキルオキシ、アルケニルまたはアルキニルであり、前記R2基が式(III)で表される化合物の中に部分Yからそれぞれメタ、パラ、およびメタとパラ位に位置しており、
・ nが1であり、
・ Xが−CH2−、−NH−S(=O)2−、−S(=O)2−NH−、−NH−C(=O)−または−C(=O)−NH−であり、
・ R6がR7−C(=O)−、R8−S(=O)2−NH−またはR8−C(=O)−NH−であり、前記R6基が式(II)で表される化合物の中に互いに隣接して位置、即ち部分Xからそれぞれメタとパラ位またはオルソとメタ位に位置し、
・ mが2であり、
・ R7がヒドロキシまたはアルキルオキシであり、
・ R8がハロゲン、ブロモ、クロロ、アルキル、アルキルオキシ、ハロアルキル、アルケニル、アルキニルで置換されているアリールであり、前記アリール基上の前記置換基が前記アリール基の結合点からそれぞれメタもしくはパラ位に位置する。
スキーム1
種類1−Aの化合物、例えばアントラニル酸などをTHFの如き溶媒および水に溶解させておいた塩基、例えばK2CO3またはNa2CO3などと混合した後、前記混合物に化合物1−Bを添加する。撹拌を室温で数時間行うと化合物1−Cが生じる。高純度の化合物1−Cをその溶液から得る目的で、前記混合物を酸性にした後、溶媒、例えば酢酸エチルなどを用いた抽出を適用する。次に、化合物1−Cに還元を例えばPd/Cと水素を用いて溶媒、例えばアルコールであるエタノールまたはメタノールなど中で受けさせる。その後、混合を室温で行いそして濾過を行った後に溶媒を除去することで、化合物1−Dを得る。化合物1−Eを添加し、そして1番目の段階と同様にしてTHF、K2CO3またはNa2CO3および水を用いることで、化合物1−Fを最終的に得る。
0.5gの化合物5−Aを25mlのTHFに入れることで生じさせた室温の混合物に水を5mlおよび炭酸ナトリウムを745mg加えた。この混合物を30分間撹拌した後、2.2当量の化合物5−BをTHF(5ml)に入れて滴下した。この反応混合物を3時間撹拌した後、濾過することで、化合物5−Cを得た。化合物5−Cを水に溶解させ、この溶液を濃塩酸溶液でpH=3になるまで酸性にした後、酢酸エチルで抽出した。その有機層を分離し、MgSO4で乾燥させた後、蒸発させることで、化合物5−Dを514mg(54%)得た。
1gの化合物6−Aを30mlのTHFに入れることで生じさせた室温の混合物に水を10mlおよび炭酸カリウムを1.57g加えた。この混合物を30分間撹拌した後、1.1当量の化合物6−Bを滴下した。この反応混合物を3時間撹拌した後、濃塩酸溶液でpH=3になるまで酸性にした。その結果として生じた溶液を酢酸エチルで抽出した。その有機層を分離し、MgSO4で乾燥させた後、蒸発させることで、化合物6−Cを503mg(32%)得た。
1.5gの化合物7−A(R1=−CN)を25mlのDMFに入れることで生じさせた室温の混合物に炭酸カリウムを5.2g(3当量)加えた。この混合物を80℃で30分間撹拌した後、化合物7−Bを2.33g加えた。この反応混合物を140℃で12時間撹拌した。反応をTLCで監視し、出発材料が消費された時点で、その混合物を室温になるまで温めた後、水を加えた。塩酸溶液をpH=3になるまで添加することでその溶液を酸性にした。生成物を酢酸エチルで抽出した。その有機層を分離し、MgSO4で乾燥させた後、蒸発させることで、化合物7−Cを3g(83%)得た。
Claims (2)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02075998 | 2002-03-11 | ||
PCT/EP2003/050055 WO2003075907A2 (en) | 2002-03-11 | 2003-03-11 | Small molecule entry inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2005526062A JP2005526062A (ja) | 2005-09-02 |
JP4627987B2 true JP4627987B2 (ja) | 2011-02-09 |
Family
ID=27798869
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003574182A Expired - Fee Related JP4627987B2 (ja) | 2002-03-11 | 2003-03-11 | 低分子侵入阻害剤 |
Country Status (18)
Country | Link |
---|---|
US (1) | US7429677B2 (ja) |
EP (1) | EP1485079B1 (ja) |
JP (1) | JP4627987B2 (ja) |
KR (1) | KR20040091722A (ja) |
CN (2) | CN1652759A (ja) |
AU (1) | AU2003219158C1 (ja) |
BR (1) | BR0308588A (ja) |
CA (1) | CA2477851C (ja) |
HR (1) | HRP20040937A2 (ja) |
IL (2) | IL163959A0 (ja) |
MX (1) | MX263097B (ja) |
NO (1) | NO20044269L (ja) |
NZ (1) | NZ535614A (ja) |
PH (1) | PH12004501358B1 (ja) |
PL (1) | PL373030A1 (ja) |
RU (1) | RU2395491C2 (ja) |
WO (1) | WO2003075907A2 (ja) |
ZA (1) | ZA200406986B (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003027255A2 (en) * | 2001-09-27 | 2003-04-03 | Tibotec Pharmaceuticals Ltd. | Anti-fusion assay |
AU2004269930B2 (en) | 2003-09-11 | 2011-08-04 | Tibotec Pharmaceuticals Ltd. | Entry inhibitors of the HIV virus |
CN1946680B (zh) * | 2004-04-23 | 2011-04-06 | 弗·哈夫曼-拉罗切有限公司 | 非核苷逆转录酶抑制剂 |
US20060025480A1 (en) | 2004-08-02 | 2006-02-02 | Boehringer Ingelheim International Gmbh | Benzoic acid derivatives as non nucleoside reverse transcriptase inhibitors |
US7569725B2 (en) | 2004-10-21 | 2009-08-04 | Britsol-Myers Squibb Company | Anthranilic acid derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase 3 |
US20100144872A1 (en) * | 2007-03-05 | 2010-06-10 | Biolipox Ab | New Methylenebisphenyl Compounds Useful in the Treatment of Inflammation |
US20110294853A1 (en) * | 2008-09-12 | 2011-12-01 | Benjamin Pelcman | Bis Aromatic Compounds for Use in the Treatment of Inflammation |
US20100109871A1 (en) * | 2008-10-31 | 2010-05-06 | General Electric Company | Rfid system and method for the same |
EP2332529A1 (de) * | 2009-12-14 | 2011-06-15 | Grünenthal GmbH | Substituierte aromatische Diamine als Liganden der vesikulären Glutamat-Transporter 1 und 2 (vGLUT1 und vGLUT2) |
CN106905184B (zh) * | 2017-03-05 | 2019-03-29 | 北京化工大学 | 含有苯甲酰胺基团的氮芥类化合物及其制备方法和用途 |
SG11202000230VA (en) | 2017-07-11 | 2020-02-27 | Vertex Pharma | Carboxamides as modulators of sodium channels |
KR102234745B1 (ko) | 2018-01-31 | 2021-04-01 | 국민대학교 산학협력단 | 메르스 코로나바이러스 헬리케이즈 nsP13의 활성을 억제하는 화합물 및 이의 용도 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR1557887A (ja) | 1968-01-05 | 1969-02-21 | ||
US3903146A (en) * | 1970-06-18 | 1975-09-02 | Leo Pharm Prod Ltd | Benzoic acid derivatives |
JPS5025003B2 (ja) * | 1971-10-26 | 1975-08-20 | ||
US5268389A (en) * | 1989-10-16 | 1993-12-07 | Uniroyal Chemical Company, Inc. | Thiocarboxylate ester compounds compositions containing the same |
DE4319039A1 (de) * | 1993-06-08 | 1994-12-15 | Bayer Ag | Substituierte (2-Oxo-1-benzimidazolinyl)-piperidine, Verfahren zu ihrer Herstellung und Verwendung als anti-retrovirale Mittel |
WO1995005170A1 (en) | 1993-08-13 | 1995-02-23 | Warner-Lambert Company | Methods of inhibiting hiv and inhibiting the activation of hiv |
WO2003005025A1 (en) * | 2001-07-03 | 2003-01-16 | Biovitrum Ab | Methods for identifying compounds modulating the activity of ppar-gamma |
-
2003
- 2003-03-11 MX MXPA04008926 patent/MX263097B/es active IP Right Grant
- 2003-03-11 AU AU2003219158A patent/AU2003219158C1/en not_active Ceased
- 2003-03-11 US US10/507,180 patent/US7429677B2/en not_active Expired - Fee Related
- 2003-03-11 NZ NZ535614A patent/NZ535614A/en unknown
- 2003-03-11 WO PCT/EP2003/050055 patent/WO2003075907A2/en active Application Filing
- 2003-03-11 IL IL16395903A patent/IL163959A0/xx unknown
- 2003-03-11 RU RU2004130295/04A patent/RU2395491C2/ru not_active IP Right Cessation
- 2003-03-11 CN CNA038102471A patent/CN1652759A/zh active Pending
- 2003-03-11 EP EP03714952.3A patent/EP1485079B1/en not_active Expired - Lifetime
- 2003-03-11 KR KR10-2004-7014257A patent/KR20040091722A/ko not_active Application Discontinuation
- 2003-03-11 BR BR0308588-0A patent/BR0308588A/pt not_active IP Right Cessation
- 2003-03-11 CN CNA2009100039975A patent/CN101519368A/zh active Pending
- 2003-03-11 JP JP2003574182A patent/JP4627987B2/ja not_active Expired - Fee Related
- 2003-03-11 CA CA002477851A patent/CA2477851C/en not_active Expired - Fee Related
- 2003-03-11 PL PL03373030A patent/PL373030A1/xx unknown
-
2004
- 2004-09-01 ZA ZA200406986A patent/ZA200406986B/en unknown
- 2004-09-03 PH PH12004501358A patent/PH12004501358B1/en unknown
- 2004-09-08 IL IL163959A patent/IL163959A/en not_active IP Right Cessation
- 2004-10-07 HR HR20040937A patent/HRP20040937A2/hr not_active Application Discontinuation
- 2004-10-08 NO NO20044269A patent/NO20044269L/no unknown
Also Published As
Publication number | Publication date |
---|---|
NZ535614A (en) | 2006-10-27 |
WO2003075907A2 (en) | 2003-09-18 |
RU2004130295A (ru) | 2005-10-27 |
HRP20040937A2 (en) | 2005-10-31 |
RU2395491C2 (ru) | 2010-07-27 |
AU2003219158A1 (en) | 2003-09-22 |
CA2477851C (en) | 2009-12-29 |
CN101519368A (zh) | 2009-09-02 |
EP1485079B1 (en) | 2014-04-02 |
KR20040091722A (ko) | 2004-10-28 |
MXPA04008926A (es) | 2004-12-13 |
PH12004501358B1 (en) | 2010-02-08 |
US20060025594A1 (en) | 2006-02-02 |
US7429677B2 (en) | 2008-09-30 |
CN1652759A (zh) | 2005-08-10 |
MX263097B (es) | 2008-12-15 |
AU2003219158B2 (en) | 2008-09-11 |
JP2005526062A (ja) | 2005-09-02 |
EP1485079A2 (en) | 2004-12-15 |
NO20044269L (no) | 2004-10-08 |
AU2003219158C1 (en) | 2009-04-02 |
CA2477851A1 (en) | 2003-09-18 |
BR0308588A (pt) | 2005-02-15 |
ZA200406986B (en) | 2005-09-22 |
IL163959A (en) | 2010-12-30 |
IL163959A0 (en) | 2005-12-18 |
PL373030A1 (en) | 2005-08-08 |
WO2003075907A3 (en) | 2004-03-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI671298B (zh) | 經取代之多環性吡啶酮衍生物及其前體藥物 | |
JP4627987B2 (ja) | 低分子侵入阻害剤 | |
BRPI0406427B1 (pt) | Processo para a preparação de roflumilast | |
TW200911817A (en) | Polycyclic guanine derivatives and methods of use thereof | |
JP2011051999A (ja) | 広域スペクトルの置換ベンズイソキサゾールスルホンアミドhivプロテアーゼ阻害剤 | |
KR20030077017A (ko) | 광범위 2-(치환된-아미노)-벤조티아졸 설폰아미드 hiv프로티아제 억제제 | |
RU2382789C2 (ru) | ПРОИЗВОДНЫЕ 1,10b-ДИГИДРО-2-(АМИНОКАРБОНИЛФЕНИЛ)-5Н-ПИРАЗОЛО[1,5-c][1,3]БЕНЗОКСАЗИН-5-ИЛ)ФЕНИЛМЕТАНОНА В КАЧЕСТВЕ ИНГИБИТОРОВ РЕПЛИКАЦИИ ВИЧ ВИРУСА | |
JP4823063B2 (ja) | Hivウイルス侵入阻害剤 | |
CN101481323A (zh) | 苯并环庚烯类衍生物、其制备方法及医药用途 | |
TW200820970A (en) | Compounds for the treatment of metabolic disorders | |
JP4578101B2 (ja) | 幅広いスペクトルのhivプロテアーゼ阻害剤である複素環置換フェニル含有スルホンアミド | |
KR20030090719A (ko) | 광범위 2-(치환된-아미노)-벤즈옥사졸 설폰아미드 hiv프로테아제 저해제 | |
JP2022519764A (ja) | 二環式スルホンアミド | |
JP4557552B2 (ja) | 広範囲置換ベンズイミダゾールスルホンアミドhivプロテアーゼ阻害剤 | |
KR20060054319A (ko) | Hiv 바이러스 침투 저해제 | |
TW202342453A (zh) | Glp-1r調節化合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20051109 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20081115 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20090128 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090224 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090522 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090529 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090818 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090915 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091215 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091222 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100304 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100406 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100728 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20100816 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20101102 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20101109 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131119 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |