25488-54-4

Upstream product

• 53900-05-3 dihydrobetulin-3β-O-acetate 
• 38736-78-6 dihydrobetulinic acid 
• 64-19-7 acetic acid 
• 75-36-5 acetyl chloride 
• 43124-92-1 (?)-3β,28-diacetoxydihydrobetulin 
• 1721-69-3 betulin diacetate 
• 473-98-3 betulin 
• 472-15-1 Betulinic acid 
• 10376-50-8 3-O-acetylbetulinic acid 

Downstream Products

• 38736-78-6 dihydrobetulinic acid 
• 4550-88-3 dihydromethylbetulinate 
• 619292-61-4 benzyl 3,O-didehydro-20,29-dihydrobetulinate 
• 203576-62-9 benzyl (3β)-3-hydroxylupan-28-oate 
• 1616704-97-2 5-(((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-1-isopropyl-3a-((S)-2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-3,3-dimethyl-5-oxopentanoic acid 
• 1616704-96-1 4-(((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-1-isopropyl-3a-((S)-2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid 
• 1616704-95-0 (1R,3S)-3-((((1S,3aS,5aR,5bR,7aR,9S,1aR,11bR,13aR,13bR)-1 isopropyl-3a-((S)-2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid 
• 1616705-58-8 1-benzyl 3-((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-1-isopropyl-3a-((S)-2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl) (1R,3S)-2,2-dimethylcyclobutane-1,3-dicarboxylate 
• 1616705-57-7 ((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-3aH-cyclopenta[a]chrysen-3a-yl)((S)-2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)methanone 
• 1616705-56-6 (1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-1-isopropyl-3a-((S)-2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl acetate 
• 1616704-94-9 (1R,3S)-3-((((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(4-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid 
• 1616704-92-7 (1R,3S)-3-((((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(4-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid 
• 1616705-55-5 1-benzyl 3-((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2 (5-(4-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)(1R,3S)-2,2-dimethylcyclobutane-1,3-dicarboxylate 
• 1616705-54-4 ((S)-2-(5-(4-fluorophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)((1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-3aH-cyclopenta[a]chrysen-3a-yl)methanone 

Relevant academic research and scientific papers

Synthesis and evaluation of anticancer activities of novel C-28 guanidine-functionalized triterpene acid derivatives

Triterpene acids, namely, 20,29-dihydrobetulinic acid (BA), ursolic acid (UA) and oleanolic acid (OA) were converted into C-28-amino-functionalized triterpenoids 4–7, 8a, 15, 18 and 20. These compounds served as precursors for the synthesis of novel guani

NOVEL TRITERPENE DERIVATIVES AS HIV INHIBITORS

The present invention relates to novel triterpene derivatives of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, n, and ring (II) are as defined in formula (I). The invention also relates to novel triterpene derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

Antimicrobial properties of amine- and guanidine-functionalized derivatives of betulinic, ursolic and oleanolic acids: Synthesis and structure/activity evaluation

A series of 34 new amine- and guanidine-functionalized derivatives of betulinic, ursolic, and oleanolic acids were synthesized and tested for their antimicrobial activity against the growth of four bacterial strains (Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus (MRSA)) and two fungal strains (Candida albicans and Cryptococcus neoformans). The obtained compounds were also tested for the cytotoxic effect against HEK293 human embryonic kidney cell line and hemolytic activity against human red blood cells. Most of the prepared amino and guanidinium derivatives of betulinic, ursolic, and oleanolic acids showed a considerably higher bacteriostatic activity against methicillin-resistant S. aureus than the parent compounds. The most active compounds (MICs ≤ 0.25 μg/ml or 0.4–0.5 μM) were superior over the clinically used antibiotic vancomycin in the antibacterial effect (MIC of 1 μg/ml or 0.7 μM). Apart from antibacterial activity, new triterpene acid derivatives exhibited excellent antifungal activity against Cryptococcus neoformans, with MICs values being as low as 0.25 μg/ml (0.4 μM), and were approximately 65 times as active as fluconazole, a known antifungal agent. Four most promising compounds we identified (7, 13, 24, and 33) showed not only high bacteriostatic effect, but also low cytotoxicity against mammalian HEK293 cells and high hemolytic selectivity.

NOVEL BETULINIC SUBSTITUTED AMIDE DERIVATIVES AS HIV INHIBITORS

The present invention relates to novel betulinic substituted amide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and are Formula (II) as defined herein. The invention novel betulinic substituted amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

Synthesis of cytotoxic 2,2-difluoroderivatives of dihydrobetulinic acid and allobetulin and study of their impact on cancer cells

In this article, we describe the preparation and cytotoxic properties of a small focused library of lupane and 18plusmn;-oleanane triterpenoids that contain a combination of two structural motifs known to enhance the biological activities. First, we introduced two fluorine atoms to position 2 of the skeleton. Second, we synthesized a set of hemiester prodrugs, which were intended to increase the solubility and activity. Starting from betulin, we obtained two hydroxyketones (derivatives of dihydrobetulinic acid and allobetulin) and their fluorination using DAST provided 2,2-difluoro-3-oxo-compounds as the main products. Then the 3-oxo group in each derivative was reduced by NaBH4 to obtain 32-hydroxy compounds suitable for modifying by various hemiesters. We prepared 21 compounds, 11 of them new, their cytotoxicity was tested on T lymphoblastic leukemia CCRF-CEM cells first and the most active derivatives were selected for screening on another six tumor and two non-tumor cell lines. All of them showed selectivity against cancer lines with therapeutic index between 2 and 8. All hemiesters had activity in the same range as the free hydroxyl derivatives and they would be suitable prodrugs for future in vivo experiments. Interestingly, all hemiesters of 2,2-difluorodihydrobetulonic acid had higher activity against p53 knock-out p53g'/g' cancer cell line than against the non-mutated analog. In active derivatives, the cell cycle was analyzed by flow cytometry and several compounds slowed down cell cycle progression through G0/G1 or S-phase.

NOVEL BETULINIC ACID PROLINE DERIVATIVES AS HIV INHIBITORS

The invention relates to novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases. These compounds are esterified in position 3 and are substituted in position 17 of the betulinic acid structure, via a linking group W, by a saturated 5-7 membered nitrogen-heterocycle.

Synthesis and cytotoxic activity of heterocyclic ring-substituted betulinic acid derivatives

A new series of betulinic acid derivatives have been synthesized by introducing heterocyclic ring between C-2 and C-3 positions of betulinic acid. Further modifications were also carried out by reduction of C-20(29) unsaturated bond and substitution of C-28 carboxyl group by ester and amide linkage to enhance the selectivity. Compound 11 resulted in IC50 of 2.44, 2.5, and 2.7 μg/ml on MIAPaCa, PA-1, and SW620 cancer cell lines, respectively. Compound 38 resulted in IC50 of 0.67 μg/ml on MIAPaCa cell line.

Synthesis and cytotoxic activity of 3-O-acyl/3-hydrazine/2-bromo/20,29- dibromo betulinic acid derivatives

A series of 3-O-acyl, 3-hydrazine, 2-bromo, and 20,29-dibromo betulinic acid derivatives (1-27) have been synthesized and screened for in vitro cytotoxic activity on human cancer cell lines MOLT-4, JurkatE6.1, CEM.CM3, BRISTOL8, U937, DU145, PA-1, A549, and L132. A number of compounds have shown ED501μg/mL against the cancer cell lines tested and have shown better cytotoxicity than betulinic acid. Compounds 13, 19, 20, 23, and 27 were the best derivatives and were selected as lead molecules for further development. The structure-activity relationship has been described.

Triterpenoid derivatives

The present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt, crystal form, complex, hydrate, or hydrolysable ester thereof, in the preparation of a medicament for treating a patient suffering from leukaemia, cancer or other proliferative disorder. A further embodiment relates to the use a compound of formula (I) in an assay for detecting the phosphorylation state of cellular substrates. The present invention also relates to novel compounds of formula (I), and the chemical synthesis thereof.

Synthesis of glycosides of lupane-type triterpene acids

A preparative synthesis of glucosides of the lupane-type triterpene acids betulinic, dihydrobetulinic, betulonic, dihydrobetulonic, and 3,20-dioxo-30-norlupan-28-oic was proposed. Glycosylation of 3-hydroxyacids by α-acetobromoglucose (ABG) with Ag2O was performed in pyridine (Py) to form glycosides at C-28, repeated glycosylation of which by these same reagents but in CH2Cl2 generated a glycoside bond at C-3 to form bisglucosides. 28-Glucosides of ketoacids were formed in high yields in both Py and CH2Cl2.