2,2,4,4,7-pentamethyl-6-aminothiochromane | 551938-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫铬烷
• 英文名称: 2,2,4,4,7-pentamethyl-6-aminothiochromane
• 英文别名: 2,2,4,4,7-pentamethyl-3H-thiochromen-6-amine
• CAS: 551938-86-4
• 化学式: C₁₄H₂₁NS
• 分子量: 235.393
• InChiKey: FTHDKZSXLFYBDU-UHFFFAOYSA-N

物化性质

• 沸点：
  353.7±42.0 °C(Predicted)
• 密度：
  1.018±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-乙氧羰基苯基硫代异氰酸酯 、 2,2,4,4,7-pentamethyl-6-aminothiochromane 以 四氢呋喃 为溶剂， 反应 24.0h， 以66%的产率得到ethyl 4-[(2,2,4,4,7-pentamethyl-3H-thiochromen-6-yl)carbamothioylamino]benzoate
  参考文献：
  名称：

  Synthesis of Flexible Sulfur-Containing Heteroarotinoids That Induce Apoptosis and Reactive Oxygen Species with Discrimination between Malignant and Benign Cells

  摘要：

  Regulation of growth, differentiation, and apoptosis by synthetic retinoids can occur through mechanisms that are dependent and independent of their ability to bind and activate nuclear retinoic acid receptors. The objective of this study was to determine if increasing flexibility of the heteroarotinoid structure would affect the specificity of the synthetic retinoids for the receptors and for their regulation of cancerous and nonmalignant cells. Methods were developed to produce the first examples of heteroarotinoids 15a-15h, which contain urea and/or thiourea linking groups between two aryl rings. Substituents at the para position of the single phenyl ring were either an ester, a nitro group, or a sulfonamide group. Ovarian cancer cell lines Caov-3, OVCAR-3, SK-OV-3, UCI-101, and 222 were utilized, and the inhibitory prowess of the heteroarotinoids was referenced to that of 4-HPR (25). Similar to 4-HPR (25), the heteroarotinoids inhibited growth of all cell lines at micromolar concentrations. Although the heteroarotinoids did not activate retinoic acid receptors, the agents induced potent growth inhibition against the cancer cells with weak activity against normal and benign cells. The growth inhibition was associated with cell loss and induction of reactive oxygen species.

  DOI：

  10.1021/jm030346v
• 作为产物：
  描述：

  2,2,4,4,7-pentamethylthiochromane 在 硝酸 、 乙酸酐 、 铁粉 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 13.5h， 生成 2,2,4,4,7-pentamethyl-6-aminothiochromane
  参考文献：
  名称：

  Synthesis of Flexible Sulfur-Containing Heteroarotinoids That Induce Apoptosis and Reactive Oxygen Species with Discrimination between Malignant and Benign Cells

  摘要：

  Regulation of growth, differentiation, and apoptosis by synthetic retinoids can occur through mechanisms that are dependent and independent of their ability to bind and activate nuclear retinoic acid receptors. The objective of this study was to determine if increasing flexibility of the heteroarotinoid structure would affect the specificity of the synthetic retinoids for the receptors and for their regulation of cancerous and nonmalignant cells. Methods were developed to produce the first examples of heteroarotinoids 15a-15h, which contain urea and/or thiourea linking groups between two aryl rings. Substituents at the para position of the single phenyl ring were either an ester, a nitro group, or a sulfonamide group. Ovarian cancer cell lines Caov-3, OVCAR-3, SK-OV-3, UCI-101, and 222 were utilized, and the inhibitory prowess of the heteroarotinoids was referenced to that of 4-HPR (25). Similar to 4-HPR (25), the heteroarotinoids inhibited growth of all cell lines at micromolar concentrations. Although the heteroarotinoids did not activate retinoic acid receptors, the agents induced potent growth inhibition against the cancer cells with weak activity against normal and benign cells. The growth inhibition was associated with cell loss and induction of reactive oxygen species.

  DOI：

  10.1021/jm030346v

文献信息

• US5498755A
  申请人：——

  公开号：US5498755A

  公开（公告）日：1996-03-12
• US6586460B1
  申请人：——

  公开号：US6586460B1

  公开（公告）日：2003-07-01
• [EN] DISUBSTITUTED ARYL AND HETEROARYL IMINES HAVING RETINOID-LIKE BIOLOGICAL ACTIVITY<br/>[FR] IMINES D'ARYLE ET D'HETEROARYLE DISUBSTITUEES AYANT UNE ACTIVITE BIOLOGIQUE ANALOGUE A CELLE DE LA RETINOÏDE
  申请人：ALLERGAN

  公开号：WO1996006070A1

  公开（公告）日：1996-02-29

  (EN) Compounds of formula (1) wherein the R1 groups independently are hydrogen, lower alkyl of 1 to 6 carbons, or two geminal R1 groups jointly represent an oxo (=O) or a thio (=S) group; R2 is hydrogen or lower alkyl of 1 to 6 carbons, or halogen; M is or -N=CR4- or -R4C=N- where R4 is hydrogen or lower alkyl of 1 - 6 carbons; X is C(R1)2, O, S, or NR1; Y is a phenyl group, or heteroaryl selected from a group consisting of pyridyl, thienyl, furyl, pyridazinyl, pirimidinyl, pyrazinyl, thiazolyl, imidazolyl and oxazolyl, said phenyl group or said heteroaryl groups being optionally substituted with an R3 group which is lower alkyl of 1 to 6 carbons or halogen; A is (CH2)n where n is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds; B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, -CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, -COR7, CR7(OR12)2, or CR7OR13O, where R7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R8 is phenyl or lower alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R11 is lower alkyl, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons have retinoid-like biological activity.(FR) L'invention se rapporte à des composés de la formule (1) dans laquelle les groupes R1 représentent indépendamment hydrogène, alkyle inférieur ayant de 1 à 6 atomes de carbone ou bien deux groupes appariés R1 représentent conjointement un groupe oxo (=o) ou un groupe thio (=S); R2 représente hydrogène ou alkyle inférieur ayant de 1 à 6 atomes de carbone ou halogène; M représente -N=CR4- ou -R4C=N- où R4 représente hydrogène ou alkyle inférieur ayant de 1 à 6 atomes de carbone; X représente C(R1)2, O, S, ou NR1; Y représente un groupe phényle ou hétéroaryle constitué par pyridyle, thiényle, furyle, pyridazinyle, pirimidinyle, pyrazinyle, thiazolyle, imidazolyle et oxazolyle, ce groupe phényle ou ces groupes hétéroaryle étant éventuellement substitués par un groupe R3 qui représente alkyle inférieur ayant de 1 à 6 atomes de carbone ou halogène; A représente (CH2)n où n vaut de 0 à 5, alkyle inférieur à chaîne ramifiée ayant de 3 à 6 atomes de carbone, cycloalkyle ayant de 3 à 6 atomes de carbone, alcényle ayant de 2 à 6 atomes de carbone et 1 ou 2 doubles liaisons ou alcynyle ayant de 2 à 6 atomes de carbone et 1 ou 2 triples liaisons; B représente hydrogène, COOH ou un sel de celui-ci pharmaceutiqement acceptable, COOR8, CONR9R10, -CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, -COR7, CR7(OR12)2, ou CR7OR13O, où R7 représente un groupe alkyle, cycloalkyle ou alcényle contenant de 1 à 5 atomes de carbone, R8 représente un groupe alkyle ayant de 1 à 10 atomes de carbone ou un groupe cycloalkyle ayant de 5 à 10 atomes de carbone, ou bien R8 représente phényle ou alkylphényle inférieur; R9 et R10 représentent indépendamment hydrogène, un groupe alkyle de 1 à 10 atomes de carbone ou un groupe cycloalkyle de 5 à 10 atomes de carbone, ou phényle ou alkylphényle inférieur, R11 représente alkyle inférieur, phényle ou alkylphényle inférieur, R12 représente alkyle inférieur et R13 est un radical alkyle divalent de 2 à 5 atomes de carbone. Ces composés ont une activité biologique analogue à celle de la rétinoïde.
• Synthesis of Flexible Sulfur-Containing Heteroarotinoids That Induce Apoptosis and Reactive Oxygen Species with Discrimination between Malignant and Benign Cells
  作者：Shengquan Liu、Chad W. Brown、K. Darrell Berlin、Aridam Dhar、Suresh Guruswamy、David Brown、Ginger J. Gardner、Michael J. Birrer、Doris M. Benbrook

  DOI：10.1021/jm030346v

  日期：2004.2.1

  Regulation of growth, differentiation, and apoptosis by synthetic retinoids can occur through mechanisms that are dependent and independent of their ability to bind and activate nuclear retinoic acid receptors. The objective of this study was to determine if increasing flexibility of the heteroarotinoid structure would affect the specificity of the synthetic retinoids for the receptors and for their regulation of cancerous and nonmalignant cells. Methods were developed to produce the first examples of heteroarotinoids 15a-15h, which contain urea and/or thiourea linking groups between two aryl rings. Substituents at the para position of the single phenyl ring were either an ester, a nitro group, or a sulfonamide group. Ovarian cancer cell lines Caov-3, OVCAR-3, SK-OV-3, UCI-101, and 222 were utilized, and the inhibitory prowess of the heteroarotinoids was referenced to that of 4-HPR (25). Similar to 4-HPR (25), the heteroarotinoids inhibited growth of all cell lines at micromolar concentrations. Although the heteroarotinoids did not activate retinoic acid receptors, the agents induced potent growth inhibition against the cancer cells with weak activity against normal and benign cells. The growth inhibition was associated with cell loss and induction of reactive oxygen species.