CN101133030A - 具有清凉性质的薄荷烷甲酰胺衍生物 - Google Patents
具有清凉性质的薄荷烷甲酰胺衍生物 Download PDFInfo
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/42—Amides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- 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
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
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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
- C07D295/04—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 substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/24—Thermal properties
- A61K2800/244—Endothermic; Cooling; Cooling sensation
Abstract
式(I)化合物,其中X和Y选自说明书中定义的基团。该化合物具有清凉性质并且可以用于例如食物、洁齿剂和化妆用品中。
Description
本发明涉及具有清凉性质的杂环化合物。
清凉化合物,即赋予身体皮肤或黏膜清凉感觉的化学化合物,已经为本领域所公知,而且其广泛用于各种产品,例如食物、烟草制品、饮料、洁齿剂、漱口剂和化妆用品中。
一类相当成功的清凉化合物包括N-取代的对-薄荷烷甲酰胺。这些化合物的例子在例如英国专利GB 1,351,761-2和美国专利US4,150,052中进行了描述。
现已发现,从这种化合物中特别选择出来的化合物显示出出人意料地强烈且长效的清凉作用。因此,本发明提供式I的化合物:
其中X和Y选自:
(i)X为H,Y选自下列基团:
或者
(ii)X和Y一起形成二价基团,所述二价基团选自-O-CH2-O-、-N=CH-O-和-N=CH-S-,从而和与其相连的碳原子一起形成5-元环(分别为1,3-二氧戊环、1,3-唑环或1,3-噻唑环)。
式I化合物的具体例子如下所示:
该化合物可以采用本领域公知的方法容易地制备和分离。
它们与现有技术中类似化合物的区别在于,其具有出人意料地高的清凉效果(最多可以比类似的已知化合物高100倍),并且该清凉效果具有长效性,因此增加了其在大量产品中的吸引力。
例如,请一小组调查对象品尝清凉化合物的各种溶液并且指出哪些溶液具有与2ppm薄荷醇溶液类似或略高的清凉强度。结果示于表1中。
表1关于清凉强度的试验
化学物质 | 浓度 |
1-薄荷醇 | 2.0ppm |
N-4-(吡唑-1-基)-苯基-3-对-薄荷烷甲酰胺 | 0.02ppm |
N-4-([1,2,4]三唑-1-基)-苯基-3-对-薄荷烷甲酰胺 | 0.02ppm |
N-3-(唑-5-基)-苯基-3-对-薄荷烷甲酰胺 | 0.1ppm |
N-4-(吗啉-4-基)-苯基-3-对-薄荷烷甲酰胺 | 0.2ppm |
N-4-(唑-5-基)-苯基-3-对-薄荷烷甲酰胺 | 0.5ppm |
N-苯并唑-4-基-3-对-薄荷烷甲酰胺 | 0.02ppm |
N-苯并[1,3]二氧戊环-5-基-3-对-薄荷烷甲酰胺 | 0.02ppm |
N-苯并噻唑-6-基薄荷烷甲酰胺 | 0.3ppm |
从表1中可以看出,式I化合物比对照清凉化合物薄荷醇的清凉作用强烈达100倍。式I清凉化合物还比WS-3的清凉作用强得多并且持续时间长,而WS-3是现有技术中最好的清凉化合物。
本发明的化合物可以在施用于口腔或皮肤的产品中使用,以便得到清凉感。“施用”是指任何形式的接触,例如口服摄取,或者对于烟草制品而言是指吸入。当施用于皮肤时,可以例如在乳霜或软膏或者在可喷式组合物中包含该化合物。因此,本发明还提供一种给口腔或皮肤提供清凉作用的方法,包括向其施用含有上述化合物的产品。本发明还提供一种给皮肤或口腔提供清凉感觉的组合物,其含有上面定义的化合物。
下面将借助以下的非限定性实施例对发明作进一步的描述,这些实施例描述了优选的实施方案。
实施例1
N-苯并唑-4-基3-对-薄荷烷甲酰胺的制备
向烧瓶中加入0.5g(3.7mmol)苯并唑-4-基胺,0.7mL三乙胺和10mL二氯甲烷。将混合物冷却至0℃并用5分钟时间滴加0.71g3-对-薄荷烷羧基氯。将反应混合物搅拌过夜。向反应混合物中加入10mL水。分离混合物。用EtOAc(3×5mL)洗涤水层。用5mL水洗涤结合起来的有机层。在Na2SO4上干燥有机层。真空蒸发溶剂得到粗产物,其经硅胶纯化得到0.46g所需产物,该产物具有下列光谱性质:
MS:300([M+]),133,97,83
1H NMR(300MHz;CDCl3)δ:8.35(s,1H),8.14(d,1H),7.68(d,1H),7.54(br.s,1H),7.18(dd,1H),2.25(t,1H),1.91-1.61(m,5H),1.5-1.23(m,2H),1.17-0.9(m,2H),0.94(d,3H),0.93(d,3H),0.85(d,3H)
实施例2
N-苯并唑-6-基3-对-薄荷烷甲酰胺的制备:
按照类似于实施例1中描述的方法进行制备,得到所需产物,其具有下列光谱性质:
MS:300([M+]),133,97,83
1H NMR(300MHz;CD3OD)δ:8.33(s,1H),8.02(m,2H),7.23(dd,1H),2.4(ddd,1H),1.88-1.54(m,5H),1.37(m,1H),1.0-1.3(m,3H),0.98(d,3H),0.86(d,3H),0.82(d,3H)
实施例3
N-苯并噻唑-6-基薄荷烷甲酰胺的制备:
按照类似于实施例1中描述的方法进行制备,得到所需产物,其具有下列光谱性质:
MS:316([M+]),150,97,83
1H NMR(300MHz;CD3OD)δ:9.12(s,1H),8.49(d,1H),7.91(d,1H),7.54(d,1H),2.2(ddd,1H),1.88-1.54(m,5H),1.21-1.47(m,4H),0.99(d,3H),0.93(d,3H),0.85(d,3H)
实施例4
N-4-([1,2,4]三唑-1-基)-苯基-3-对-薄荷烷甲酰胺的制备:
按照类似于实施例1中描述的方法进行制备,得到所需产物,其具有下列光谱性质:
MS:326([M+]),160,97,83
1H NMR(300MHz;CD3OD)δ:8.98(s,1H),8.07(s,1H),7.84(s,4H),2.26(t,1H),1.9-1.5(m,5H),1.45-1.3(m,1H),1.25-1(m,3H),0.94(d,3H),0.86(d,3H),0.8(d,3H)
实施例5
N-4-(唑-5-基)-苯基-3-对-薄荷烷甲酰胺的制备:
按照类似于实施例1中描述的方法进行制备,得到所需产物,其具有下列光谱性质:
MS:326([M+]),160,139,97,83
1H NMR(300MHz;CD3OD)δ:8.19(s,1H),7.66(s,4H),7.42(s,1H),2.35(ddd,1H),1.88-1.54(m,5H),1.4-1.35(m,1H),1.0-1.3(m,3H),0.95(d,3H),0.91(d,3H),0.84(d,3H)
实施例6
N-3-(唑-5-基)-苯基-3-对-薄荷烷甲酰胺的制备:
按照类似于实施例1中描述的方法进行制备,得到所需产物,其具有下列光谱性质:
MS:326([M+]),160,139,97,83
实施例7
在漱口剂中的应用
乙醇95% 177mL
山梨糖醇70% 290g
实施例1的化合物,其为在乙醇中形成的1%溶液 10mL
无萜薄荷油 0.300g
水杨酸甲酯 0.640g
桉油精 0.922g
百里酚 0.639g
苯甲酸 1.500g
Pluronic F127 5.000g
糖精钠 0.600g
柠檬酸钠 0.300g
柠檬酸 0.100g
水 适量至1升
混合所有成分。将30mL所得溶液放入口腔中,来回搅动、漱口并吐出。口腔的每一区域及嘴唇都感到非常清凉。清凉感觉持续数小时。
实施例8
在牙膏中的应用
不透明牙凝胶 98.000g
实施例6的化合物,其为在PG中的2%溶液 1.500g
无萜薄荷油 0.500g
将化合物混合在牙凝胶中,将一条牙凝胶放于牙刷上并且让调查对象用于刷牙。用水漱口并且将水吐出。调查对象口腔中的每一区域都感觉到强烈的清凉感。清凉感持续数小时。
Claims (4)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65756205P | 2005-03-01 | 2005-03-01 | |
US60/657,562 | 2005-03-01 | ||
PCT/CH2006/000116 WO2006092074A1 (en) | 2005-03-01 | 2006-02-23 | Menthane carboxamide derivatives having cooling properties |
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Publication Number | Publication Date |
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CN101133030A true CN101133030A (zh) | 2008-02-27 |
CN101133030B CN101133030B (zh) | 2010-07-28 |
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CN200680006684XA Expired - Fee Related CN101133030B (zh) | 2005-03-01 | 2006-02-23 | 具有清凉性质的薄荷烷甲酰胺衍生物 |
Country Status (12)
Country | Link |
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US (1) | US7868004B2 (zh) |
EP (1) | EP1853565B1 (zh) |
JP (1) | JP2008531606A (zh) |
KR (1) | KR20070107083A (zh) |
CN (1) | CN101133030B (zh) |
AT (1) | ATE482199T1 (zh) |
BR (1) | BRPI0607407A2 (zh) |
CA (1) | CA2597415A1 (zh) |
DE (1) | DE602006017038D1 (zh) |
ES (1) | ES2352563T3 (zh) |
MX (1) | MX2007010040A (zh) |
WO (1) | WO2006092074A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102325749A (zh) * | 2009-02-19 | 2012-01-18 | 奇华顿股份有限公司 | 作为风味剂的香叶基胺衍生物 |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
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CN100582089C (zh) | 2003-11-21 | 2010-01-20 | 吉万奥丹股份有限公司 | N-取代的对-薄荷烷甲酰胺 |
ATE443046T1 (de) * | 2005-10-25 | 2009-10-15 | Givaudan Sa | Organische verbindungen |
US20100056636A1 (en) * | 2006-12-20 | 2010-03-04 | Stefan Michael Furrer | N-Substituted-P-Menthane-3-Carboxamide and Uses Thereof |
WO2009076792A1 (en) * | 2007-12-19 | 2009-06-25 | Givaudan Sa | Cooling compounds |
EP2250154A1 (en) * | 2008-01-17 | 2010-11-17 | Givaudan SA | Benzimidazole derivatives and their use as cooling agents |
GB201103103D0 (en) | 2011-02-23 | 2011-04-06 | Givaudan Sa | Organic compounds |
EP2497458A1 (en) | 2011-03-08 | 2012-09-12 | B.R.A.I.N. Biotechnology Research And Information Network AG | Small molecule modulators of the cold and menthol receptor TRPM8 |
EP3134080A1 (en) | 2014-04-23 | 2017-03-01 | The Procter & Gamble Company | Cyclohexanecarboxamide with cooling properties |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
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GB1351761A (en) * | 1971-02-04 | 1974-05-01 | Wilkinson Sword Ltd | Substituted p-menthane carboxamides and compositions containing them |
US5918309A (en) * | 1997-10-14 | 1999-07-06 | Second Chance Body Armor, Inc. | Blunt force resistant structure for a protective garment |
BR0315686B1 (pt) * | 2002-10-28 | 2014-04-29 | Givaudan Sa | Soluções consistindo em lactato de mentila e mentol carboxamida,seu método de preparação, composição alimentícia, de cuidado bucal ou cosmética, bem como método para melhorar a solubilidade de lactato de mentila |
AU2004253582B2 (en) * | 2003-07-02 | 2011-02-10 | Genentech, Inc. | TRP-P8 active compounds and therapeutic treatment methods |
JP5335191B2 (ja) | 2003-08-22 | 2013-11-06 | デンドレオン コーポレイション | Trp−p8発現に関連する疾患の処置をするための組成物および方法 |
CN100582089C (zh) * | 2003-11-21 | 2010-01-20 | 吉万奥丹股份有限公司 | N-取代的对-薄荷烷甲酰胺 |
GB0425661D0 (en) | 2004-11-23 | 2004-12-22 | Givaudan Sa | Organic compounds |
US8673198B2 (en) * | 2006-02-18 | 2014-03-18 | Honeywell International Inc | Method of making improved ballistic products |
-
2006
- 2006-02-23 WO PCT/CH2006/000116 patent/WO2006092074A1/en active Application Filing
- 2006-02-23 MX MX2007010040A patent/MX2007010040A/es not_active Application Discontinuation
- 2006-02-23 KR KR1020077019793A patent/KR20070107083A/ko not_active Application Discontinuation
- 2006-02-23 DE DE602006017038T patent/DE602006017038D1/de active Active
- 2006-02-23 ES ES06705356T patent/ES2352563T3/es active Active
- 2006-02-23 AT AT06705356T patent/ATE482199T1/de not_active IP Right Cessation
- 2006-02-23 EP EP06705356A patent/EP1853565B1/en not_active Not-in-force
- 2006-02-23 CA CA002597415A patent/CA2597415A1/en not_active Abandoned
- 2006-02-23 CN CN200680006684XA patent/CN101133030B/zh not_active Expired - Fee Related
- 2006-02-23 JP JP2007557307A patent/JP2008531606A/ja active Pending
- 2006-02-23 US US11/884,479 patent/US7868004B2/en not_active Expired - Fee Related
- 2006-02-23 BR BRPI0607407-3A patent/BRPI0607407A2/pt not_active Application Discontinuation
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102325749A (zh) * | 2009-02-19 | 2012-01-18 | 奇华顿股份有限公司 | 作为风味剂的香叶基胺衍生物 |
CN102325749B (zh) * | 2009-02-19 | 2014-11-12 | 奇华顿股份有限公司 | 作为风味剂的香叶基胺衍生物 |
Also Published As
Publication number | Publication date |
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ES2352563T3 (es) | 2011-02-21 |
EP1853565A1 (en) | 2007-11-14 |
DE602006017038D1 (de) | 2010-11-04 |
CN101133030B (zh) | 2010-07-28 |
ATE482199T1 (de) | 2010-10-15 |
BRPI0607407A2 (pt) | 2009-09-01 |
US7868004B2 (en) | 2011-01-11 |
CA2597415A1 (en) | 2006-09-08 |
MX2007010040A (es) | 2007-09-21 |
EP1853565B1 (en) | 2010-09-22 |
WO2006092074A1 (en) | 2006-09-08 |
JP2008531606A (ja) | 2008-08-14 |
KR20070107083A (ko) | 2007-11-06 |
US20080305051A1 (en) | 2008-12-11 |
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