194720-19-9

Upstream product

• 32981-86-5 10-deacetylbaccatin III 
• 994-30-9 triethylsilyl chloride 

Downstream Products

• 259522-65-1 7,10,13-tri(triethylsilyl)-2-debenzoyl-2-(3-methoxybenzoyl)-10-deacetylbaccatin III 
• 930785-77-6 C₆₇H₉₁NO₁₅Si₂ 
• 930786-00-8 C₆₅H₉₅NO₁₆Si₂ 
• 930786-02-0 C₆₃H₉₁NO₁₆Si₂ 
• 941672-26-0 C₅₁H₈₆O₁₁Si₄ 
• 941672-24-8 C₅₀H₈₆O₁₁Si₄ 
• 930785-81-2 C₅₀H₅₃NO₁₅ 
• 930785-79-8 C₅₀H₅₃NO₁₅ 
• 941672-25-9 C₄₈H₈₄O₁₀Si₄ 
• 930786-04-2 C₄₈H₅₇NO₁₆ 
• 930785-76-5 C₃₉H₅₄O₁₂Si 
• 941672-28-2 C₃₃H₄₀O₁₂ 
• 941672-27-1 C₃₁H₃₈O₁₁ 
• 925211-29-6 2-debenzoyl-2-(p-fluorobenzoyl)-4-deacetyl-4-(d3-acetyl)-10-deacetylbaccatin 

Relevant academic research and scientific papers

Synthesis and biological evaluation of novel 3′-difluorovinyl taxoids

A series of 3′-difluorovinyl taxoids with C10 modifications, as well as those with C2 and C10 modifications, were strategically designed to block the metabolism by cytochrome P-450 3A4 enzyme and synthesized. These novel difluorovinyl taxoids were evaluated for their cytotoxicity against drug-sensitive human breast (MCF7), multidrug-resistant (MDR) human ovarian (NCI/ADR), human colon (HT-29) and human pancreatic (PANC-1) cancer cell lines. 3′-Difluorovinyl taxoids exhibit several to 16 times better activity against MCF7, HT-29 and PANC-1 cell lines and up to three orders of magnitude higher potency against NCI/ADR cell line as compared to paclitaxel. Structure-activity relationship study shows the critical importance of the C2 modifications on the activity against MDR cancer cell line, while the C10 modifications have a rather minor effect on the potency with some exceptions. The effect of the C2 modifications on potency against MCF7 cell line increases in the following order: H 3. Among the twenty five 3′-difluorovinyl taxoids evaluated, eight taxoids exhibited less than 100 pM IC50 values against MCF7 cell line. Difluorovinyl taxoids induced GTP-independent tubulin polymerization much faster than paclitaxel. Then, the resulting microtubules were stable to Ca2+-induced depolymerization, indicating strong stabilization of microtubules. Molecular modeling study indicated that a difluorovinyl taxoid binds to β-tubulin in a manner that is consistent with the REDOR-Taxol structure. The difluorovinyl group appears to mimic the isobutenyl group to some extent, but with very different electronic property, which may account for the unique activities of difluorovinyl taxoids.

Design, synthesis and biological evaluation of novel fluorinated docetaxel analogues

A series of novel fluorinated docetaxel analogues have been synthesized and evaluated in vitro and in vivo. Incorporated one, two or three fluorine atom(s) either at both meta position on C-2 benzolate and 3′-N-tert-butyloxyl group or only at 3′-N-tert-butyloxyl group has resulted in potent analogues which have comparable or superior in vitro and in vivo cytotoxicity to docetaxel. Among them, compounds 14d and 14e have displayed more potent cytotoxicity than docetaxel both in human cancer cell line SK-OV-3 in vitro and in human non-small cell lung cancer A549 xenografts in vivo. Preliminary data show that compound 14a has reduced acute animal toxicity in mice compared with docetaxel.

Syntheses and structure-activity relationships of novel 3′-difluoromethyl and 3′-trifluoromethyl-taxoids

A series of novel 3′-difluoromethyl-taxoids and 3′-trifluoromethyl-taxoids with modifications at the C2 and C10 positions were synthesized and evaluated for their in vitro cytotoxicities against human breast carcinoma (MCF7-S, MCF7-R, LCC6-WT, LCC6-MDR),

Design, synthesis, and biological evaluation of new-generation taxoids

Novel second-generation taxoids with systematic modifications at the C2, C10, and C3′N positions were synthesized and their structure-activity relationships studied. A number of these taxoids exhibited exceptionally high potency against multidrug-resistan

Rotational-echo double-resonance NMR distance measurements for the tubulin-bound paclitaxel conformation

The important anticancer drug Taxol (paclitaxel, PTX) owes its unique activity to its ability to bind to tubulin in a stoichiometric ratio and promote its assembly into microtubules. The conformation of the microtubule-bound drug has been the focus of num

Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents

A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure - activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

Synthesis and biological evaluation of novel taxoids designed for targeted delivery to tumors

The use of drug-antibody conjugates affords a method for the targeted delivery of anticancer drugs specifically to cancer cells. Monoclonal antibodies alone usually do not possess high therapeutic efficacy, however, they are capable of targeting tumor mar

Structure-activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

A series of new taxoids modified at the C-3′, C-3′N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mφ) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mφ-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mφ. Positions C-3′ and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3′N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN Mφ and the cytotoxicity against Mφ-like cells.

Macrocycle formation by ring-closing metathesis. Application to the syntheses of novel macrocyclic taxoids

A series of novel macrocyclic taxoids 6 and 6′ bearing 16-, 17-, and 18-membered rings connecting the substituants at the C-2 and C-3′ positions were designed and synthesized. The syntheses of these macrocycles 6 and 6′ were accomplished using the highly

Synthesis of paclitaxel (docetaxel) / 2-deacetoxytaxinine J dimers

Starting from taxanes available in multigram amounts from widespread ornamental yews (10-deacetylbaccatin III (4) and 2'-deacetoxyaustrospicatine (5)), two dimeric taxoids (3a, 3b) with potential dual target specificity (β-tubulin and P-gp) were synthesised. Both compounds lacked significant cytotoxicity, though 3b retained a strong activity in the tubulin depolimerisation assay.