JP3711131B2 - 新規のシクロヘキシルスルホン - Google Patents
新規のシクロヘキシルスルホン Download PDFInfo
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- JP3711131B2 JP3711131B2 JP2003523207A JP2003523207A JP3711131B2 JP 3711131 B2 JP3711131 B2 JP 3711131B2 JP 2003523207 A JP2003523207 A JP 2003523207A JP 2003523207 A JP2003523207 A JP 2003523207A JP 3711131 B2 JP3711131 B2 JP 3711131B2
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- 0 C=*c(cc1)c(C(CC2)(CCC2=O)S(=O)=O)cc1F Chemical compound C=*c(cc1)c(C(CC2)(CCC2=O)S(=O)=O)cc1F 0.000 description 2
- UYAWPFMDLYTQME-UHFFFAOYSA-N O=S(C1C=CC(Cl)=CC1)=O Chemical compound O=S(C1C=CC(Cl)=CC1)=O UYAWPFMDLYTQME-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/20—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- 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
- C07D213/24—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
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- 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
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Description
mは0または1であり、
ZはCN、OR2a、CO2R2aまたはCON(R2a)2を表し、
R1bはH、C1〜4アルキルまたはOHを表し、
R1cはHまたはC1〜4アルキルを表し、
Ar1はフェニルまたはピリジルを表し、そのどちらもが、ハロゲン、CN、NO2、CF3、OH、OCF3、C1〜4アルコキシまたはC1〜4アルキル(ハロゲン、CN、NO2、CF3、OHおよびC1〜4アルコキシから選択された置換基を場合によっては有する)から独立して選択された0〜3個の置換基を有し、
Ar2はハロゲンにより2位および5位で置換されているフェニルを表し、
R2aは、H、C1〜6アルキル、C3〜6シクロアルキル、C3〜6シクロアルキルC1〜6アルキル、C2〜6アルケニルを表し、それらのうち任意のものが、ハロゲン、CN、NO2、CF3、OR2b、CO2R2b、N(R2b)2、CON(R2b)2、ArおよびCOArから選択された置換基を場合によっては有しているか;あるいは、R2aはArを表すか;あるいは、2個のR2a基は、それらが共通して結合している窒素原子と一緒になって、=O、=S、ハロゲン、C1〜4アルキル、CN、NO2、CF3、OH、C1〜4アルコキシ、C1〜4アルコキシカルボニル、CO2H、アミノ、C1〜4アルキルアミノ、ジ(C1〜4アルキル)アミノ、カルバモイル、ArおよびCOArから独立して選択された0〜4個の置換基を有するN−複素環基を完成してもよく、
R2bは、H、C1〜6アルキル、C3〜6シクロアルキル、C3〜6シクロアルキルC1〜6アルキル、C2〜6アルケニルを表し、それらのうち任意のものが、ハロゲン、CN、NO2、CF3、OH、C1〜4アルコキシ、C1〜4アルコキシカルボニル、CO2H、アミノ、C1〜4アルキルアミノ、ジ(C1〜4アルキル)アミノ、カルバモイル、ArおよびCOArから選択された置換基を場合によっては有するか;あるいは、R2bはArを表すか;あるいは、2個のR2b基は、それらが共通して結合している窒素原子と一緒になって、=O、=S、ハロゲン、C1〜4アルキル、CN、NO2、CF3、OH、C1〜4アルコキシ、C1〜4アルコキシカルボニル、CO2H、アミノ、C1〜4アルキルアミノ、ジ(C1〜4アルキル)アミノ、カルバモイル、ArおよびCOArから独立して選択された0〜4個の置換基を有するN−複素環基を完成してもよく、
Arは、ハロゲン、C1〜4アルキル、CN、NO2、CF3、OH、C1〜4アルコキシ、C1〜4アルコキシカルボニル、アミノ、C1〜4アルキルアミノ、ジ(C1〜4アルキル)アミノ、カルバモイル、C1〜4アルキルカルバモイルおよびジ(C1〜4アルキル)カルバモイルから選択された0〜3個の置換基を有するフェニルまたはヘテロアリールを表す]で表される化合物、またはその製薬上許容される塩を提供する。
また、油状物として、流出の遅いトランス異性体を得た(200mg、5.3%)。
モルホリンの代わりに適当なアミンを用いて、実施例3の方法に従って以下の化合物を調製した。
DCM(50ml)および酢酸エチル(30ml)に溶解させた実施例2の酸(1g)の溶液にペンタフルオロフェノール(1.5当量)およびDCC(1.5当量)を添加し、1時間室温で撹拌した。この反応混合物を真空で蒸発させ、酢酸エチルに加え、濾過した。濾液を真空内で蒸発させ、後続の反応で用いるのに十分な精製のペンタフルオロフェノールエステルを得た。
窒素下、DMF(3ml)に溶解させたステップ(1)で調製したペンタフルオロフェノールエステル(155mg、0.25 mmol)にグリシンメチルエステル塩酸塩(125mg、1.0mmol)およびトリエチルアミン(0.15ml)を添加した。2時間後、この反応物を水で希釈し、酢酸エチルで抽出し(×3)、水、ブラインで洗浄し、乾燥させ(MgSO4)、濾過し、蒸発させた。フラッシュカラムクロマトグラフイー(1:1=iヘキサン/酢酸エチルから9:1=酢酸エチル/メタノール)によって精製し、白色固形物(55mg)を得た。1H NMR(CDCl3)1.08〜1.16(1H,m)、1.30〜1.37(1H,m)、1.67〜1.71(1H,m)、1.75〜1.79(2H,m)、1.91〜1.95(1H,m)、2.20〜2.26(1H,m)、2.41(4H,d,J=7.8Hz)、3.77(3H,s)、4.05(2H,d,J=5.1Hz)、6.19(1H,br)、6.79〜6.85(1H,m)、7.00〜7.07(2H,m)、7.30〜7.37(4H,m)。
MS(EI+)477(MH+)。
Claims (7)
- mが1であり、Ar1が4−クロロフェニルを表し、R1cがHを表し、ZがCO2Hを表す請求項1に記載の化合物、あるいはその製薬上許容される塩。
- mが1であり、Ar1が4−トリフルオロメチルフェニルを表し、R1cがHを表し、ZがCO2Hを表す請求項1に記載の化合物、あるいはその製薬上許容される塩。
- ナトリウム塩の形態である請求項2または3に記載の化合物。
- 請求項1から3のいずれか一項に記載の化合物、またはその製薬上許容される塩、および製薬上許容される担体を含む医薬組成物。
- 人体の治療方法で使用するための請求項1から3のいずれか一項に記載の化合物、またはその製薬上許容される塩。
- アルツハイマー病を治療または予防するための薬剤の製造における請求項1から3のいずれか一項に記載の化合物、またはその製薬上許容される塩の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/GB2001/003741 WO2002081435A1 (en) | 2001-04-05 | 2001-08-21 | Sulphones which modulate the action of gamma secretase |
GBGB0120347.0A GB0120347D0 (en) | 2001-08-21 | 2001-08-21 | Therapeutic agents |
PCT/GB2002/003806 WO2003018543A1 (en) | 2001-08-21 | 2002-08-16 | Novel cyclohexyl sulphones |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2005501120A JP2005501120A (ja) | 2005-01-13 |
JP3711131B2 true JP3711131B2 (ja) | 2005-10-26 |
JP2005501120A5 JP2005501120A5 (ja) | 2005-12-22 |
Family
ID=26245715
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003523207A Expired - Lifetime JP3711131B2 (ja) | 2001-08-21 | 2002-08-16 | 新規のシクロヘキシルスルホン |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP1421062B1 (ja) |
JP (1) | JP3711131B2 (ja) |
AU (1) | AU2002324123B2 (ja) |
CA (1) | CA2456420A1 (ja) |
DK (1) | DK1421062T3 (ja) |
EA (1) | EA006225B1 (ja) |
HK (1) | HK1061838A1 (ja) |
HR (1) | HRP20040075B1 (ja) |
HU (1) | HUP0401241A3 (ja) |
IS (1) | IS2497B (ja) |
MX (1) | MXPA04001607A (ja) |
WO (1) | WO2003018543A1 (ja) |
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GB0218041D0 (en) * | 2002-08-02 | 2002-09-11 | Merck Sharp & Dohme | Chemical process |
GB0223039D0 (en) | 2002-10-04 | 2002-11-13 | Merck Sharp & Dohme | Therapeutic compounds |
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TW200920362A (en) | 2007-09-11 | 2009-05-16 | Daiichi Sankyo Co Ltd | Alkylsulfone derivatives |
EP2222636B1 (en) | 2007-12-21 | 2013-04-10 | Ligand Pharmaceuticals Inc. | Selective androgen receptor modulators (sarms) and uses thereof |
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US8461389B2 (en) | 2008-04-18 | 2013-06-11 | University College Dublin, National University Of Ireland, Dublin | Psycho-pharmaceuticals |
EP2413932A4 (en) | 2009-04-01 | 2012-09-19 | Merck Sharp & Dohme | INHIBITORS OF AKT ACTIVITY |
BR112012008849A2 (pt) | 2009-10-14 | 2015-09-22 | Schering Corp | composto, composição farmacêutica, e, uso de um composto |
EP2584903B1 (en) | 2010-06-24 | 2018-10-24 | Merck Sharp & Dohme Corp. | Novel heterocyclic compounds as erk inhibitors |
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HK1061838A1 (en) | 2004-10-08 |
HUP0401241A3 (en) | 2008-03-28 |
IS7125A (is) | 2004-01-26 |
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AU2002324123B2 (en) | 2007-07-12 |
IS2497B (is) | 2009-02-15 |
HRP20040075A2 (en) | 2004-08-31 |
MXPA04001607A (es) | 2004-07-08 |
WO2003018543A1 (en) | 2003-03-06 |
EA200400331A1 (ru) | 2004-08-26 |
JP2005501120A (ja) | 2005-01-13 |
EP1421062B1 (en) | 2007-11-21 |
CA2456420A1 (en) | 2003-03-06 |
DK1421062T3 (da) | 2008-02-18 |
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