4-(4-methylnaphthalen-1-yl)thiazol-2-amine | 332064-25-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(4-methylnaphthalen-1-yl)thiazol-2-amine
• 英文别名: 4-(4-methyl-naphthalen-1-yl)-thiazol-2-ylamine；4-(4-methylnaphthalen-1-yl)-1,3-thiazol-2-amine
• CAS: 332064-25-2
• 化学式: C₁₄H₁₂N₂S
• 分子量: 240.329
• InChiKey: ILUMXAZUDODMRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-methylnaphthalen-1-yl)thiazol-2-amine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 18.08h， 以34%的产率得到(1S,8R)-16-methyl-16-N-[4-(4-methylnaphthalen-1-yl)-1,3-thiazol-2-yl]tetracyclo[6.6.2.02,7.09,14]hexadeca-2(7),3,5,9,11,13-hexaene-3,16-dicarboxamide
  参考文献：
  名称：

  Heterocyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-kB activity and use thereof

  摘要：

  该发明涉及一类新型非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括肥胖、糖尿病、炎症和免疫性疾病，并具有如下结构的化学式(I)或其立体异构体、前药、溶剂合物或药用可接受盐，其中Z、R、R4、R5、Ra、Rb、Rc和Rd在此处定义。还提供了包含所述化合物的药物组合物和治疗肥胖、糖尿病以及炎症或免疫相关疾病的方法。

  公开号：

  US20060154962A1
• 作为产物：
  描述：

  甲基萘 在 aluminum (III) chloride 、 phenyltrimethylammonium tribromide 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 22.0h， 生成 4-(4-methylnaphthalen-1-yl)thiazol-2-amine
  参考文献：
  名称：

  [EN] NEUROPROTECTIVE COMPOSITIONS AND METHODS OF USING THE SAME
  [FR] COMPOSITIONS NEUROPROTECTRICES ET LEURS MÉTHODES D'UTILISATION

  摘要：

  这项发明涉及神经保护性组合物和使用这些组合物治疗神经退行性疾病的方法。

  公开号：

  WO2019222393A1

文献信息

• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Weinstein David S.

  公开号：US20090075995A1

  公开（公告）日：2009-03-19

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R 5 , R 6 , R 7 , and R 8 ; J 1 , J 2 , and J 3 are at each occurrence the same or different and are independently -A 1 QA 2 -; Q is a bond, O, S, S(O), or S(O) 2 ; A 1 and A 2 are the same or different and are at each occurrence independently selected from a bond, C 1-3 alkylene, substituted C 1-3 alkylene, C 2-4 alkenylene, and substituted C 2-4 alkenylene, provided that A 1 and A 2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R 1 to R 11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

  提供了一系列新颖的非甾体化合物，这些化合物在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病中很有用，包括炎性和免疫疾病，具有以下结构式（I）： 其对应的光学异构体、对映异构体或互变异构体，或其前药酯，或其药用可接受盐，其中： Z是杂环或杂芳基； A是一个5至8成员的碳环或一个5至8成员的杂环； B是一个环烷基、环烯基、芳基、杂环或杂芳基环，其中每个环都与A环上的相邻原子融合，并且可以选择性地被一个到四个独立选自R5、R6、R7和R8的相同或不同的组取代； J1、J2和J3每次出现时相同或不同，独立地选自-A1QA2-；Q是键、O、S、S(O)或S(O)2；A1和A2相同或不同，每次出现时独立地选自键、C1-3烷基、取代的C1-3烷基、C2-4烯基和取代的C2-4烯基，前提是A1和A2的选择使得环A是一个5至8成员的碳环或杂环； R1至R11如本文所述定义。 还提供了使用这些化合物的药物组合物和治疗炎性疾病、免疫相关疾病、肥胖和糖尿病的方法。
• Tricyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-kB activity and use thereof
  申请人：Weinstein S. David

  公开号：US20050187242A1

  公开（公告）日：2005-08-25

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein B, J, K, Z, R, R a , R b , R c , R d , R q , R w , m and n are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

  提供了一种新型的非甾体化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括肥胖、糖尿病、炎症和免疫性疾病，并具有以下结构的化学式（I）或其立体异构体或前药或其药用可接受盐，其中B、J、K、Z、R、Ra、Rb、Rc、Rd、Rq、Rw、m和n在此处被定义。还提供了包含所述化合物的药物组合物和治疗肥胖、糖尿病以及炎症或免疫相关疾病的方法。
• [EN] MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF<br/>[FR] MODULATEURS DU RECEPTEUR DES GLUCOCORTICOIDES AP-1, ET/OU DE L'ACTIVITE DU NF-KB ET UTILISATION ASSOCIEE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2005072729A1

  公开（公告）日：2005-08-11

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF­ KB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I), its stereoisomers thereof, or a solvate thereof, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, where Z is CONR1R2 or CH2 NR1R2 and where R, R', Ra, Rb, Rc, Rd, Z, A and B are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF­ KB活性调节相关的疾病，包括肥胖、糖尿病、炎症和免疫性疾病，其结构如下式（I），其立体异构体，或其溶剂化物，或其前药，或其药用可接受的盐，其中Z为CONR1R2或CH2 NR1R2，其中R、R'、Ra、Rb、Rc、Rd、Z、A和B在此处定义。还提供了含有该化合物的药物组合物和治疗肥胖、糖尿病以及炎症或免疫相关疾病的方法。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KAPPABETA ACTIVITY AND USE THEREOF
  申请人：Yang Bingwei Vera

  公开号：US20100004219A1

  公开（公告）日：2010-01-07

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory or immune associated diseases or disorders having the structure of formula I or an enantiomer, diastereomer, tautomer, or a pharmaceutically-acceptable salt, thereof, wherein: A is a 5-, 6-, or 7-membered heterocyclo or heteroaryl, each containing 1, 2, or 3 heteroatoms selected from N, O, and S and substituted with one to four groups, R 1 , R 2 , R 3 , and/or R 4 , provided that (i) A is not tetrazole or (ii) if A is thienyl or furanyl then Z is selected from a group other than succinimido or thalimido; M is selected from alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl; Ma is a linker between C and M and is selected from a bond and C 1 -C 3 alkylene; Q is selected from (i) hydrogen, halogen, nitro, cyano, hydroxy, C 1 -4alkyl, and substituted C 1 -4 alkyl; or (ii) Q is combined with R6 and with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and M are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO 2 , and N which ring may be optionally substituted with 0-2 R 5 groups or carbonyl; and Z is selected from alkyl, CF 3 , OH, cycloalkyl, heterocyclo, aryl, heteroaryl, —C(═O)NR 8 R 9 , —C(═O)R 8 , —C(NCN)NR 8 R 9 , —C(═O)OR 8 , —SO 2 R 8 , and —SO2NR8R9. M a , Z a , R 1 , R 2 , R 3 , R5 a , R 6 , R 7 , R 8 , R 9 and R 22 are as defined herein. Also provided are pharmaceutical compositions, combinations and methods of treating metabolic and inflammatory or immune associated diseases or disorders using said compounds.

  本发明提供了一些新型非甾体化合物，其可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括代谢和炎症或免疫相关疾病或障碍。该化合物具有公式I或其对映异构体、顺反异构体、互变异构体或药学上可接受的盐，其中：A是5、6或7元杂环或杂环芳基，每个都含有1、2或3个从N、O和S中选择的杂原子，并取代有1至4个基团R1、R2、R3和/或R4，但（i）A不是四氮唑或（ii）如果A是噻吩基或呋喃基，则Z是选择自除琥珀酰亚胺或萘酰亚胺之外的一组；M选择自烷基、环烷基、芳基、杂环烷和杂环芳基；Ma是C和M之间的连接器，选择自键和C1-C3烷基；Q选择自（i）氢、卤素、硝基、氰基、羟基、C1-4烷基和取代的C1-4烷基；或（ii）Q与R6以及它们附着的碳原子结合形成3-至6元环烷基；或（iii）Q和M与它们附着的碳原子结合形成3-至7元环，其中包含1-2个杂原子，这些杂原子独立地选择自O、S、SO2和N的群，该环可以选择性地取代0-2个R5基团或羰基；Z选择自烷基、CF3、OH、环烷基、杂环烷基、芳基、杂环芳基、-C（=O）NR8R9、-C（=O）R8、-C（NCN）NR8R9、-C（=O）OR8、-SO2R8和-SO2NR8R9。Ma、Za、R1、R2、R3、R5a、R6、R7、R8、R9和R22的定义如本文所述。还提供了使用所述化合物的制药组合物和治疗代谢和炎症或免疫相关疾病或障碍的方法。
• Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
  申请人：Bristol-Myers Squibb Company

  公开号：US07968577B2

  公开（公告）日：2011-06-28

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I) an enantiomer, diastereomer, tautomer, solvate (e.g. a hydrate), or a pharmaceutically-acceptable salt, thereof, wherein: M is selected from alkyl, substituted alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl, provided that if M is alkyl then R6 and R7 taken together with the carbon atom to which they are both attached are selected from a group other than cycloalkyl; Q is selected from (i) hydrogen, C1-C4 alkyl, and substituted C1-C4 alkyl; or (ii) Q and R6 are combined with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and MaM are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO2, and N which ring may be optionally substituted with 0-2 R5 groups or carbonyl; Z is selected from cycloalkyl, heterocyclo, aryl, or heteroaryl; and Ma, Za, R1, R2, R3, R4, R6, R7, and R22 are as defined herein. Also provided are pharmaceutical compositions and methods of treating metabolic and inflammatory- or immune-associated diseases or disorders using said compounds.

  提供了一种新型的非类固醇化合物，其在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病方面具有用途，包括炎症和免疫性疾病、肥胖症和糖尿病，其结构式（I）的对映体、顺反异构体、互变异构体、溶剂化物（例如水合物）或其药学上可接受的盐，其中：M选自烷基、取代烷基、环烷基、芳基、杂环烷基和杂环芳基，但如果M是烷基，则R6和R7与它们都附着的碳原子一起选自不是环烷基的一组；Q选自（i）氢、C1-C4烷基和取代的C1-C4烷基；或（ii）Q和R6与它们附着的碳原子结合形成3-至6-环环烷基；或（iii）Q和MaM与它们附着的碳原子结合形成3-至7-环环，其中包含1-2个杂原子，这些杂原子独立地选自O、S、SO2和N的一组，并且该环可以选择性地用0-2个R5基团或羰基取代；Z选自环烷基、杂环烷基、芳基或杂环芳基；Ma、Za、R1、R2、R3、R4、R6、R7和R22如本文所定义。还提供了药物组合物和使用所述化合物治疗代谢和炎症或免疫相关疾病或疾病的方法。