40283-05-4

Upstream product

• 1693-05-6 ethyl 4-(4'-fluorophenyl)butanoate 
• 589-06-0 4-(4-fluorophenyl)butanoic acid 
• 20637-05-2 methyl 4-(4-fluorophenyl)butanoate 
• 70250-73-6 4-(4-fluorophenyl)but-3-yn-1-ol 
• 366-77-8 4-(4-fluorophenyl)-4-oxopropionic acid 
• 1736-67-0 4-fluorophenylacetaldehyde 

Downstream Products

• 89326-70-5 1-bromo-4-(4-fluorophenyl)-butane 
• 30087-09-3 Phosphoric acid 2,2-dichloro-vinyl ester 4-(4-fluoro-phenyl)-butyl ester methyl ester 
• 925442-73-5 4-(4-fluorophenyl)butan-1-al 
• 1281859-78-6 6-benzyl-1-(4-(4-fluorophenyl)butoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1281859-81-1 6-benzyl-1-(4-(4-fluorophenyl)butoxymethyl)-3-hydroxy-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1281859-86-6 6-benzyl-1-(4-(4-fluorophenyl)butyl)-5-isopropyl-3-(2-oxo-2-phenylethyl)pyrimidine-2,4(1H,3H)-dione 
• 1281859-89-9 6-benzyl-1-(4-(4-fluorophenyl)butyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1281859-92-4 6-benzyl-1-(4-(4-fluorophenyl)butyl)-3-hydroxy-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 220728-25-6 2-[4-(4-fluorophenyl)butyl]isoindoline-1,3-dione 
• 1089672-20-7 4-(4-fluorophenyl)butyl methanesulfonate 
• 89347-14-8 6-(4-Fluoro-phenyl)-hexanoic acid (8R,9S,10R,13S,14S,17R)-17-ethynyl-13-methyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester 
• 89326-71-6 ethyl 2-ethoxycarbonyl-6-(4'-fluorophenyl)hexanoate 
• 89326-76-1 6-(4-Fluoro-phenyl)-hexanoyl chloride 

Relevant academic research and scientific papers

Discovery and evaluation of nNav1.5 sodium channel blockers with potent cell invasion inhibitory activity in breast cancer cells

Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and the important roles that they play in excitable cells. Recently, their presence has been recognized in non-excitable cells such as cancer cells and their overexpression has been shown to be associated with metastatic behavior in a variety of human cancers. The neonatal isoform of the VGSC subtype, Nav1.5 (nNav1.5) is overexpressed in the highly aggressive human breast cancer cell line, MDA-MB-231. The activity of nNav1.5 is known to promote the breast cancer cell invasion in vitro and metastasis in vivo, and its expression in primary mammary tumors has been associated with metastasis and patient death. Metastasis development is responsible for the high mortality of breast cancer and currently there is no treatment available to specifically prevent or inhibit breast cancer metastasis. In the present study, a 3D-QSAR model is used to assist the development of low micromolar small molecule VGSC blockers. Using this model, we have designed, synthesized and evaluated five small molecule compounds as blockers of nNav1.5-dependent inward currents in whole-cell patch-clamp experiments in MDA-MB-231 cells. The most active compound identified from these studies blocked sodium currents by 34.9 ± 6.6% at 1 μM. This compound also inhibited the invasion of MDA-MB-231 cells by 30.3 ± 4.5% at 1 μM concentration without affecting the cell viability. The potent small molecule compounds presented here have the potential to be developed as drugs for breast cancer metastasis treatment.

Enantioselective Intermolecular C-H Amination Directed by a Chiral Cation

The enantioselective amination of C(sp3)-H bonds is a powerful synthetic transformation yet highly challenging to achieve in an intermolecular sense. We have developed a family of anionic variants of the best-in-class catalyst for Rh-catalyzed C-H amination, Rh2(esp)2, with which we have associated chiral cations derived from quaternized cinchona alkaloids. These ion-paired catalysts enable high levels of enantioselectivity to be achieved in the benzylic C-H amination of substrates bearing pendant hydroxyl groups. Additionally, the quinoline of the chiral cation appears to engage in axial ligation to the rhodium complex, providing improved yields of product versus Rh2(esp)2 and highlighting the dual role that the cation is playing. These results underline the potential of using chiral cations to control enantioselectivity in challenging transition-metal-catalyzed transformations.

GLYCOSIDE COMPOUND AND PREPARATION METHOD THEREFOR, COMPOSITION, APPLICATION, AND INTERMEDIATE

The present invention discloses a glycoside compound represented by Formula III, and a preparation method, a composition, use and an intermediate thereof. The glycoside compound provided in the present invention has simple preparation method, can significantly increase the expression of VEGF-A mRNA, and is effective in promoting the angiogenesis. This provides a reliable guarantee for the development of drugs with pro-angiogenic activity for treating cerebral infarction cerebral stroke, myocardial infarction, and ischemic microcirculatory disturbance of lower limbs.

Targeting an Aromatic Hotspot in Plasmodium falciparum 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase with β-Arylpropyl Analogues of Fosmidomycin

Blocking the 2-C-methyl-d-erythrithol-4-phosphate pathway for isoprenoid biosynthesis offers new ways to inhibit the growth of Plasmodium spp. Fosmidomycin [(3-(N-hydroxyformamido)propyl)phosphonic acid, 1] and its acetyl homologue FR-900098 [(3-(N-hydroxyacetamido)propyl)phosphonic acid, 2] potently inhibit 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in this biosynthetic pathway. Arylpropyl substituents were introduced at the β-position of the hydroxamate analogue of 2 to study changes in lipophilicity, as well as electronic and steric properties. The potency of several new compounds on the P. falciparum enzyme approaches that of 1 and 2. Activities against the enzyme and parasite correlate well, supporting the mode of action. Seven X-ray structures show that all of the new arylpropyl substituents displace a key tryptophan residue of the active-site flap, which had made favorable interactions with 1 and 2. Plasticity of the flap allows substituents to be accommodated in many ways; in most cases, the flap is largely disordered. Compounds can be separated into two classes based on whether the substituent on the aromatic ring is at the meta or para position. Generally, meta-substituted compounds are better inhibitors, and in both classes, smaller size is linked to better potency.

Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies

Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads.

BENZOXAZOLONE DERIVATIVES AS ACID CERAMIDASE INHIBITORS, AND THEIR USE AS MEDICAMENTS

The present invention relates to benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides benzoxazolone derivatives for use as a medicament in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.

3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase

Integrase (IN) represents a clinically validated target for the development of antivirals against human immunodeficiency virus (HIV). Inhibitors with a novel structure core are essential for combating resistance associated with known IN inhibitors (INIs). We have previously disclosed a novel dual inhibitor scaffold of HIV IN and reverse transcriptase (RT). Here we report the complete structure-activity relationship (SAR), molecular modeling, and resistance profile of this inhibitor type on IN inhibition. These studies support an antiviral mechanism of dual inhibition against both IN and RT and validate 3-hydroxypyrimidine-2,4-diones as an IN inhibitor scaffold.

Discovery of a highly orally bioavailable c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carbo xylic acid as a potent hypoglycemic and hypolipidemic agent

A series of novel 1,3-dioxane-2-carboxylic acid derivatives containing alkyl chain tether and substituted phenyl group as a lipophilic tail have been prepared as agonists of PPARα and γ. c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carbo xylic acid 13c exhibited potent hypoglycemic and lipid lowering activity with high oral bioavailability in animal models.

CHEMICAL COMPOUNDS

The invention provides compounds formula I, their preparation, and their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, a