4-[2-(5,5,8,8-四甲基-5,6,7,8-四氢萘-2-基)-1,3-二噻戊环-2-基]苯甲酸 | 146670-37-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 4-[2-(5,5,8,8-四甲基-5,6,7,8-四氢萘-2-基)-1,3-二噻戊环-2-基]苯甲酸
• 英文名称: 4-(2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,3-dithiolan-2-yl)benzoic acid
• 英文别名: NMP0305；SR11234；[2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-2-(4-carboxyphenyl)]-1,3-dithiolane；4-(2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-(1,3)dithiolan-2-yl)benzoic acid；4-[2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)-1,3-dithiolan-2-yl]benzoic acid
• CAS: 146670-37-3
• 化学式: C₂₄H₂₈O₂S₂
• 分子量: 412.617
• InChiKey: NWFLPURWUQNLIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  87.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氯甲酰基苯甲酸甲酯 在 氢氧化钾 、 三氯化铝 、 三氟化硼乙醚 作用下， 以 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 4-[2-(5,5,8,8-四甲基-5,6,7,8-四氢萘-2-基)-1,3-二噻戊环-2-基]苯甲酸
  参考文献：
  名称：

  Conformational Effects on Retinoid Receptor Selectivity. 2. Effects of Retinoid Bridging Group on Retinoid X Receptor Activity and Selectivity

  摘要：

  The natural retinoid 9-cis-retinoic acid is an activating ligand for both the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are members of the retinoid/thyroid hormone/steroid hormone family of nuclear receptor proteins that activate gene transcription through specific response elements. The pharmacophoric groups necessary to confer RXR selectivity were established by evaluating the ability of 21 conformationally restricted retinoids to activate, the TREpal retinoic acid receptor response element for gene transcription in the presence of one of the three RAR subtypes or RXR alpha. In contrast to those retinoids selective for the RARs, these RXR-selective retinoids have one less atom in the bridge linking the hydrophobic and carboxylic acid termini of the retinoid skeleton. Therefore, a one-carbon bridge replaces the 19-methyl group and SE-double bond of S-cis-retinoic acid and is further functionalized by inclusion in an isopropylidene group, a dioxolane ring, or a cyclopropane ring for optimal RXR alpha activity and selectivity. In addition, the beta-geranylidene and 20-methyl-(11E,13E)-dienoic acid groups of g-cis-retinoic acid are replaced by a 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphthalenyl ring and a 4-carboxylphenyl ring, respectively, for optimal activation and selectivity. RXR alpha; selectivity is reduced on replacement of the 4-carboxylphenyl group by a 2-carboxyl-5-thienyl group or the S-cis-retinoic acid methylpentadienoic acid terminus.

  DOI：

  10.1021/jm00017a021

文献信息

• Development and Characterization of Novel and Selective Inhibitors of Cytochrome P450 CYP26A1, the Human Liver Retinoic Acid Hydroxylase
  作者：Philippe Diaz、Weize Huang、Charles M. Keyari、Brian Buttrick、Lauren Price、Nicolas Guilloteau、Sasmita Tripathy、Vanessa G. Sperandio、Frank R. Fronczek、Fanny Astruc-Diaz、Nina Isoherranen

  DOI：10.1021/acs.jmedchem.5b01780

  日期：2016.3.24

  and CYP26B1 is unknown, and no selective CYP26A1 or CYP26B1 inhibitors have been developed. Here the synthesis and potent inhibitory activity of the first CYP26A1 selective inhibitors is reported. A series of nonazole CYP26A1 selective inhibitors was identified with low nM potency. The lead compound 3-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,3-dioxolan-2-yl] phenyl}4-propanoic

  细胞色素P450 CYP26酶负责全反式维甲酸（t RA）的清除。抑制CYP26酶会增加内源性t RA浓度，并且是有吸引力的治疗靶标。但是，尚不存在现有的t RA代谢抑制剂对CYP26A1和CYP26B1的选择性和效力，因此尚未开发出选择性的CYP26A1或CYP26B1抑制剂。此处报道了首批CYP26A1选择性抑制剂的合成和强抑制活性。鉴定出一系列的nazole CYP26A1选择性抑制剂具有低nM效能。铅化合物3- 4- [2-（5,5,8,8-四甲基-5,6,7,8-四氢萘-2-基）-1,3-二氧戊环-2-基]苯基} 4 -丙酸（24）对CYP26A1有43倍的选择性，IC 50为340 nM。化合物24及其两个结构类似物也抑制了HepG2细胞中的t RA代谢，导致t RA增强RAR激活的能力。所鉴定的化合物具有成为旨在提高内源性t RA浓度的新型治疗方法的潜力，并且可用作与t RA共同治疗以抵抗治疗耐药性的方法。
• NOVEL AND SPECIFIC INHIBITORS OF CYTOCHROME P450 26 RETINOIC ACID HYDROXYLASE
  申请人：UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION

  公开号：US20160200703A1

  公开（公告）日：2016-07-14

  The present disclosure is generally directed to compositions and methods for treating diseases that are ameliorated by the inhibition of CYP26 mediated retinoic acid metabolism. The compositions comprise compounds of formula (I). A repreid50000060307390 IB/345 nullsents aryl optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —OH, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy; X is a bond, —CH 2 —, —CHR 5 —, —C═CHR 4 —, —NR 4 —, —N═O—R 4 —, —O—, —S—, —SO—, —SO 2 —, —C(O)—, or —C(NR 4 )—, or X is of formula (a), (b) or (c), wherein each n is independently 1, 2, or 3; each R 4 is independently hydrogen or C 1-6 alkyl; R 5 is independently hydrogen, C 1-6 alkyl, or —OR 6 , where R 6 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyL C 3-12 cycloalkyl, heterocyclyl, aryl, arylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6 alkyl; Y is C 1-6 alkylene, C 2-6 alkenylene, or C 2-6 alkylylene moiety.

  本公开涉及的是组合物和治疗方法，用于治疗通过抑制CYP26介导的视黄酸代谢而改善的疾病。这些组合物包括公式（I）的化合物。其中，芳基可选地取代为一个、两个、三个或四个基团，每个基团独立地为卤素、氰基、硝基、C1-6烷基、C1-6卤代烷基、-NH2、-NH（C1-C6烷基）、-N（C1-C6烷基）2、-OH、C1-C6烷氧基和C1-C6卤代烷氧基；X为键，-CH2-，-CHR5-，-C═CHR4-，-NR4-，-N═O-R4-，-O-，-S-，-SO-，-SO2-，-C（O）-或-C（NR4）-，或X为公式（a）、（b）或（c），其中每个n独立地为1、2或3；每个R4独立地为氢或C1-6烷基；每个R5独立地为氢、C1-6烷基或-OR6，其中R6选自由氢基、C1-6烷基、C2-6烯基、C2-6炔基、C3-12环烷基、杂环基、芳基、芳基C1-6烷基、杂芳基或杂芳基C1-6烷基；Y为C1-6烷基、C2-6烯基或C2-6烷基亚基。
• SYSTEMS AND METHODS FOR ENHANCING VACCINE EFFICACY
  申请人：Phipps Richard P.

  公开号：US20110300129A1

  公开（公告）日：2011-12-08

  Pharmaceutical compositions of the invention include an antigen or a nucleic acid molecule encoding the antigen; one or both of a PPAR ligand and an RxR ligand; and a pharmaceutically suitable carrier. The pharmaceutical composition can optionally include a mitogen or other additives. Also disclosed are methods of inducing B cell differentiation and promoting an immune response against an antigen.
• US5837725A
  申请人：——

  公开号：US5837725A

  公开（公告）日：1998-11-17
• US9963439B2
  申请人：——

  公开号：US9963439B2

  公开（公告）日：2018-05-08