Deltasonamide 2 (TFA)
目录号 : GC35837
Deltasonamide 2 TFA 是一种竞争性的，高亲和力的 PDEδ 抑制剂，Kd 值约为 385 pM。
Cas No.:2235358-74-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Deltasonamide 2 TFA is competitive, high affinity PDEδ inhibitor with a Kd of ~385 pM[1]. Kd: ~385 pM (PDEδ)[1]
[1]. Klein CH, et al. PDEδ inhibition impedes the proliferation and survival of human colorectal cancer cell linesharboring oncogenic KRas. Int J Cancer. 2019 Feb 15;144(4):767-776.
| Cas No. | 2235358-74-2 | SDF | |
| Canonical SMILES | O=S(C1=CC=C(S(=O)(N(CC2=CC=C(Cl)C=C2)C3CCCC3)=O)C=C1)(N([C@H]4CC[C@H](N)CC4)CC5=NC(NC)=NC=C5)=O.O=C(O)C(F)(F)F | ||
| 分子式 | C32H40ClF3N6O6S2 | 分子量 | 761.27 |
| 溶解度 | DMSO: 125 mg/mL (164.20 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3136 mL | 6.568 mL | 13.1359 mL |
| 5 mM | 0.2627 mL | 1.3136 mL | 2.6272 mL |
| 10 mM | 0.1314 mL | 0.6568 mL | 1.3136 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Halogenated D-xylono-δ-lactams: synthesis and enzyme inhibition study
Carbohydr Res 2015 Jan 30;402:215-24.PMID:25498022DOI:10.1016/j.carres.2014.10.023.
A concise synthesis of four C-3 fluoro/chloro-D-xylono-δ-lactams 3/4 has been reported. The methodology involves Corey-Link approach with suitably protected 3-oxo-D-gluco-furanose to introduce F/Cl as well as ester/amide functionalities at C-3 of glucose. In next steps, 5,6-O-isopropylidene group was converted to the 5-azido xylosugars that on opening of 1,2-acetonide group, and intramolecular Schmidt-Boyer reaction with TFA/H2O, in one pot, afforded lactams 3/4. Conformational aspect of δ-lactams was studied by the 1H NMR spectroscopy. The halogenated δ-lactams 3/4 showed no inhibition against different glycosidase enzymes.
Histone Deacetylases Regulation by δ-Opioids in Human Optic Nerve Head Astrocytes
Invest Ophthalmol Vis Sci 2020 Sep 1;61(11):17.PMID:32915982DOI:10.1167/iovs.61.11.17.
Purpose: We determined whether δ-opioid receptor agonist (SNC-121) regulates acetylation homeostasis via controlling histone deacetylases (HDACs) activity and expression in optic nerve head (ONH) astrocytes. Methods: ONH astrocytes were treated with SNC-121 (1 µM) for 24 hours. The HDAC activity was measured using HDAC-specific fluorophore-conjugated synthetic substrates, Boc-Lys(Ac)-AMC and (Boc-Lys(TFA)-AMC). Protein and mRNA expression of each HDAC was determined by Western blotting and quantitative real-time PCR. IOP in rats was elevated by injecting 2.0 M hypertonic saline into the limbal veins. Results: Delta opioid receptor agonist, SNC-121 (1 µM), treatment increased acetylation of histone H3, H2B, and H4 by 128 ± 3%, 45 ± 1%, and 68 ± 2%, respectively. The addition of Garcinol, a histone-acetyltransferase inhibitor, fully blocked SNC-121-induced histone H3 acetylation. SNC-121 reduced the activities of class I and IIb HDACs activities significantly (17 ± 3%) and this decrease in HDACs activities was fully blocked by a selective δ-opioid receptors antagonist, naltrindole. SNC-121 also decrease the mRNA expression of HDAC-3 and HDAC-6 by 19% and 18%, respectively. Furthermore, protein expression of HDAC 1, 2, 3, and 6 was significantly (P < 0.05) decreased by SNC-121 treatment. SNC-121 treatment also reduced lipopolysaccharide-induced TNF-α production from ONH astrocytes and glial fibrillary acidic protein immunostaining in the optic nerve of ocular hypertensive animals. Conclusions: We provided evidence that δ-opioid receptor agonist activation increased histone acetylation, decrease HDACs class I and class IIb activities, mRNA, and protein expression, lipopolysaccharide-induced TNF-α production in ONH astrocytes. Our data also demonstrate that SNC-121 treatment decrease glial fibrillary acidic protein immunostaining in the optic nerves of animals with ocular hypertension.
Cyclic enkephalin-deltorphin hybrids containing a carbonyl bridge: structure and opioid activity
Acta Biochim Pol 2011;58(2):225-30.PMID:21584287doi
Six hybrid N-ureidoethylamides of octapeptides in which an N-terminal cyclic structure related to enkephalin was elongated by a C-terminal fragment of deltorphin were synthesized on MBHA resin. The synthetic procedure involved deprotection of Boc groups with HCl/dioxane and cleavage of the peptide resin with 45 % TFA in DCM. d-Lys and d-Orn were incorporated in position 2, and Lys, Orn, Dab, or Dap in position 5. The side chains of the dibasic amino function were protected with the Fmoc group. This protection was removed by treatment with 55 % piperidine in DMF, and cyclization was achieved by treatment with bis-(4-nitrophenyl)carbonate. Using various combinations of dibasic amino acids, peptides containing a 17-, 18-, 19- or 20-membered ring structure were obtained. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse opioid activities were observed, depending on the size of the ring. Extension of the enkephalin sequence at the C-terminus by a deltorphin fragment resulted in a change of receptor selectivity in favor of the δ receptor. The conformational propensities of selected peptides were determined using the EDMC method in conjunction with data derived from NMR experiments carried out in water. This approach allowed proper examination of the dynamical behavior of these small peptides. The results were compared with those obtained earlier with corresponding N-(ureidoethyl)pentapeptide amides.
1,3,5-Tri- and 1,3,4,5-tetra-substituted 1,4-diazepin-2-one solid-phase synthesis
J Comb Chem 2008 Sep-Oct;10(5):691-9.PMID:18687008DOI:10.1021/cc8001052.
Solid-phase syntheses of 1,3,5-tri-substituted and 1,3,4,5-tetra-substituted 1,4-diazepin-2-ones 15-18 have been accomplished by employing inexpensive commercially available alpha- and beta-amino acids on Wang resin. Reductive amination of the imine formed by condensation of Wang aldehyde resin respectively with beta-alaninate 2 and beta-homophenylalaninate 3, followed by aminoacylation with a set of alpha-N-Boc amino acids (Phe epsilon-( Z)-Lys, and Leu) gave tertiary amide resins 7 and 8. Exposure of resins 7 and 8 to an excess of vinyl magnesium bromide in the presence of copper cyanide gave the corresponding gamma,delta-unsaturated ketone resins 9 and 10 by way of a cascade addition. Diazepinones were made by Boc deprotection and intramolecular reductive amination. To diversify the heterocycle, N-alkylation was performed using a series of alkyl halides. Alternatively, diazepinones 15e-g were obtained from treatment of methyl beta-alaninate resins 4 and 20 under similar copper-catalyzed cascade conditions to afford the gamma,delta-unsaturated ketone 21, which was acylated using alpha-N-Fmoc-amino acids (Phe, Trp, gamma-(t-Bu)-Glu). Formation of diazepinones 15 followed a similar protocol, after Fmoc removal with piperidine. Cleavage of the heterocycles with TFA/TES 95:5 gave the N1-p-hydroxybenzyl diazepinones 15-18 in overall isolated yields from 6 to 24% after purification in purities ranging from 81 to 100% according to LCMS analysis.
Organophosphorus reagents in organocatalysis: synthesis of optically active α-methylene-δ-lactones and δ-lactams
Chemistry 2012 Aug 13;18(33):10348-54.PMID:22706879DOI:10.1002/chem.201201325.
In this paper we describe new asymmetric, catalytic strategies for the synthesis of biologically important α-methylene-δ-lactones and δ-lactams. The elaborated protocols utilize iminium-ion-mediated Michael addition of trimethyl phosphonoacetate to α,β-unsaturated aldehydes catalyzed by (S)-(-)-α,α-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether as the key step. Enantiomerically enriched Michael adducts are employed in three different reaction pathways. Transformation into α-methylene-δ-lactones is realized by a sequence of reactions involving chemoselective reduction of the aldehyde, followed by a trifluoroacetic acid (TFA)-mediated cyclization and Horner-Wadsworth-Emmons olefination of formaldehyde. On the other hand, indolo[2,3-a]quinolizine-framework-containing products can be accessed when enantiomerically enriched Michael adducts are employed in a Pictet-Spengler reaction with tryptamine, followed by Horner-Wadsworth-Emmons olefination. Finally, reductive amination of the Michael adducts by using methylamine and Horner-Wadsworth-Emmons olefination of formaldehyde is demonstrated to give α-methylene-δ-lactams. The developed strategies can be realized without the purification of intermediates, thus greatly increasing their practicality.