218600-50-1

Usage

Uses

Used in Pharmaceutical Industry:
Olean-9(11)-en-28-oic acid, 3,12-dioxo-, methyl ester (9CI) is used as a pharmaceutical compound for its potential therapeutic applications. Its unique structure and properties make it a candidate for the development of new drugs, particularly in the area of steroid-based medications.
Used in Chemical Research:
In the field of chemical research, Olean-9(11)-en-28-oic acid, 3,12-dioxo-, methyl ester (9CI) serves as a subject of study for understanding the properties and behavior of steroidal compounds. Its complex structure provides insights into the chemistry of organic molecules and their potential applications in various industries.
Used in Industrial Applications:
Olean-9(11)-en-28-oic acid, 3,12-dioxo-, methyl ester (9CI) is utilized in industrial applications where its specific chemical properties are required. Its presence in specialized settings suggests that it may be used in the synthesis of other compounds or as an intermediate in the production of various products.

InChI:InChI=1/C31H46O4/c1-26(2)13-15-31(25(34)35-8)16-14-30(7)24(19(31)18-26)20(32)17-22-28(5)11-10-23(33)27(3,4)21(28)9-12-29(22,30)6/h17,19,21,24H,9-16,18H2,1-8H3/t19-,21-,24-,28-,29+,30+,31-/m0/s1

Upstream product

• 65023-19-0 methyl 3β-hydroxy-12-oxoolean-9(11)-en-28-oate 
• 4339-72-4 oleanolic acid 3-acetate 
• 25493-69-0 (4aS,6aS,6bR,10S,12aR)-methyl 10-acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylate 
• 508-02-1 Oleanolic acid 
• 1724-17-0 oleanolic acid methyl ester 
• 25493-94-1 methyl 3-O-β-acetyl-11-dehydro-12-oxo-18β-oleanolate 
• 65023-20-3 methyl 3β-acetoxy-12-oxoolean-9(11)-en-28-oate 

Downstream Products

• 305818-40-0 1,2-dihydro-2-cyano-3,12-dioxooleana-1,9⁽¹¹⁾-dien-28-oic acid methyl ester 
• 218600-53-4 bardoxolone methyl 
• 218600-44-3 bardoxolone 
• 218600-52-3 methyl 12-oxoisoxazolo[4,5-b]olean-9⁽¹¹⁾-en-28-oate 
• 305818-39-7 methyl 2-hydroxymethylene-3,12-dioxoolean-9⁽¹¹⁾-en-28-oate 

Relevant academic research and scientific papers

Design and Synthesis of Irreversible Analogues of Bardoxolone Methyl for the Identification of Pharmacologically Relevant Targets and Interaction Sites

Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro. We show that one of these analogues, CDDO-epoxide (13), is comparable to 4 in terms of cytotoxicity and potency toward Nrf2 in rat hepatoma cells and stably modifies specific cysteine residues (namely, Cys-257, -273, -288, -434, -489, and -613) within Keap1, the major repressor of Nrf2, both in vitro and in living cells. Supported by molecular modeling, these data demonstrate the value of 13 for identifying site(s) of interaction with pharmacologically relevant targets and informing the continuing development of triterpenoids as novel drug candidates.

Therapeutic compounds and methods of use

Compounds and methods useful for chemopreventative treatment of diseases such as cancer, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, and multiple sclerosis.

Efficient and scalable synthesis of bardoxolone methyl (CDDO-methyl ester)

Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti-inflammatory activity (levels below 1 nM), has completed a successful phase I clinical trial for the treatment of cancer and a successful phase II trial for the treatment of chronic kidney disease in type 2 diabetes patients. Our synthesis of bardoxolone methyl (1) proceeds in ～50% overall yield in five steps from oleanolic acid (2), requires only one to two chromatographic purifications, and can provide gram quantities of 1.

Synthetic oleanane and ursane triterpenoids with modified rings A and C: A series of highly active inhibitors of nitric oxide production in mouse macrophages

We have designed and synthesized 16 new olean- and urs-1-en-3-one triterpenoids with various modified rings C as potential antiinflammatory and cancer chemopreventive agents and evaluated their inhibitory activities against production of nitric oxide induced by interferon-γ in mouse macrophages. This investigation revealed that 9(11)-en-12-one and 12-en-11-one functionalities in ring C increase the potency by about 2-10 times compared with the original 12-ene. Subsequently, we have designed and synthesized novel olean- and urs-1-en-3-one derivatives with nitrile and carboxyl groups at C-2 in ring A and with 9(11)-en-12-one and 12-en-11-one functionalities in ring C. Among them, we have found that methyl 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oate (25), 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) (26), and methyl 2-carboxy-3,12-dioxooleana-1,9(11)-dien-28-oate (29) have extremely high potency (IC50 = 0.1 nM level). Their potency is similar to that of dexamethasone although they do not act through the glucocorticoid receptor. Overall, the combination of modified rings A and C increases the potency by about 10 000 times compared with the lead compound, 3-oxooleana-1,12-dien-28-oic acid (8) (IC50 = 1 μM level). The selected oleanane triterpenoid, CDDO (26), was found to be a potent, multifunctional agent in various in vitro assays and to show antiinflammatory activity against thioglycollate-interferon-γ-induced mouse peritonitis.

Design and synthesis of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, a novel and highly active inhibitor of nitric oxide production in mouse macrophages

New derivatives with electron-withdrawing substituents at the C-2 position of 3-oxoolean-1-en-28-oic acid were synthesized. Among them, 2- cyano-3,12-dioxoleam-1,9-dien-28-oic acid (CDDO) was 400 times more potent than previous compounds we have made as an inhibitor of production of nitric oxide induced by interferon γ in mouse macrophages (IC50, 0.4 nM). The potency of CDDO was similar to that of dexamethasone, although CDDO does not act through the glucocorticoid receptor.

New enone derivatives of oleanolic acid and ursolic acid as inhibitors of nitric oxide production in mouse macrophages

New derivatives of 3-oxoolean-1-en-28-oic acid and 3-oxours-1-en-28-oic acid were synthesized. Nine of them showed significant inhibitory activity against interferon-γ-induced nitric oxide production in mouse macrophages when assayed at the 1 μM level. 3,12-Dioxoolean-1,9-dien-28-oic acid (3) had the highest activity (IC50, 0.9 μM).