BARDOXOLONE METHYL

• Molecular FormulaC₃₂H₄₃NO₄
• Average mass505.688 Da

Methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate

methyl 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oate

2-Cyano-3,12-dioxoolean-1,9(11)-dien-28-oic acid methyl ester
(6aR,6bS,8aR,12aS,14aR,14bS)-11-Cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-hexadecahydropicene-4a(2H)-carboxylic acid methyl ester

BARD
CDDO-Me
Methyl-CDDO
NSC-713200
RTA-402
TP-155C

218600-53-4  ^CAS

218600-44-3 (free acid)

Compounds were synthesized as below:

Scheme 1

Scheme 2

a: HCO₂Et/MeONa/THF,b: PhSeCl/AcOEt; 30%H₂0₂/THF,c: NH₂OH-HCI EtOH/H₂O, d: MeONa/MeOH/Et₂O,e: KOH/MeOH,f: Jones,g:HCO₂Et/MeONa/PhH,h: Lil/DMF Compound 10 was prepared by formylation of OA (Compound 9) (Simonsen and Ross, 1957) with ethyl formate in the presence of sodium methoxide in THF (Clinton et al., 1961). Compound 7 was obtained by introduction of a double bond at C-l of Compound 10 with phenylselenenyl chloride in ethyl acetate and sequential addition of 30%) hydrogen peroxide (Sharpless et al, 1973). Compound 11 was synthesized from Compound 10 by addition of hydroxylamine in aqueous ethanol; cleavage of Compound 11 with sodium methoxide gave Compound 12 (Johnson and Shelberg, 1945). Compound 14 was prepared from Compound 13 (Picard et al, 1939) by alkali hydrolysis followed by Jones oxidation. Compound 15 was prepared by formylation of Compound 14 with ethyl formate in the presence of sodium methoxide in benzene. Compound 16 was synthesized from Compound 15 by addition of hydroxylamine. Cleavage of 16 with sodium methoxide gave Compound 17. Compound 6 (CDDO) was prepared by introduction of a double bond at C-l of Compound 17 with phenylselenenyl chloride in ethyl acetate and sequential addition of 30% hydrogen peroxide, followed by halogenolysis with lithium iodide in DMF (Dean, P.D.G., 1965).

Bardoxolone methyl (also known as “RTA 402” and “CDDO-methyl ester”) is an orally-available first-in-class synthetic triterpenoid. It is an inducer of the Nrf2 pathway, which can suppress oxidative stress and inflammation, and is undergoing clinical development for the treatment of advanced chronic kidney disease (CKD) in type 2 diabetes mellitus patients.

Bardoxolone methyl was previously being investigated by Reata Pharmaceuticals, Inc. in partnership with Abbott Laboratories and Kyowa Hakko Kirin, as an experimental therapy for advanced chronic kidney disease (CKD) in type 2 diabetes mellitus patients. Reata, in consultation with the BEACON Steering Committee, has decided to terminate the Phase 3 BEACON trial of bardoxolone methyl in patients with stage 4 chronic kidney disease and type 2 diabetes. This decision was made based upon a recommendation of the Independent Data Monitoring Committee (IDMC) to stop the trial “for safety concerns due to excess serious adverse events and mortality in the bardoxolone methyl arm.” ^[1][2][3][4]

RTA-402 is a triterpenoid anti-inflammatory agent in phase II trials at Reata Pharmaceuticals for the treatment of pulmonary arterial hypertension.

This company and M.D. Anderson Cancer Center had been evaluating clinically the product for the treatment of lymphoma. Reata had been evaluating the compound in combination with gemcitabine in patients with unresectable pancreatic cancer and melanoma. Preclinical studies were also being conducted by Reata for the treatment of inflammatory bowel disease (IBD) and autoimmune disease. Reata Pharmaceuticals and Kyowa Hakko Kirin had been conducting phase II clinical studies for the treatment of diabetic nephropathy. Reata and Abbott also had been conducting phase III clinical trials for delaying progression to end-stage renal disease in patients with chronic kidney disease and type 2 diabetes; however, in 2012 these trials were discontinued due to serious adverse events and mortality. Phase II clinical trials for this indication were discontinued by Kyowa Hakko Kirin in Japan. The compound had been in early clinical studies for the treatment of multiple myeloma; however, no recent development has been reported for this indication. Phase I clinical trials for the treatment of solid tumors have been completed.

RTA-402 has demonstrated a wide variety of potentially therapeutic mechanisms, including inhibition of inducible nitric oxide synthase and cyclooxygenase expression, stimulation of expression of cytoprotective enzymes such as NAD(P)H quinine oxidoreductase and hemeoxygenase-1, and reduction in pSTAT3 levels. In cancer patients, the drug candidate exploits fundamental physiological differences between cancerous and non-cancerous cells by modulating oxidative stress response pathways. Due to this mechanism, RTA-402 is toxic to cancer cells, but induces protective antioxidant and anti-inflammatory responses in normal cells. In previous studies, the compound was shown to inhibit growth and cause regression of cancerous tumors as a single agent and, in combination with radiation and chemotherapy, to suppress radiation and chemotherapy-induced toxicities in normal tissues and cause minimal toxicity in non-human primates when dosed orally at very high doses for 28 consecutive days.

An analog of RTA-401, RTA-402 is a compound found in medicinal plants with a greater potency than the natural product.

RTA-401 was originally developed at Dartmouth College and M.D. Anderson Cancer Center. In November 2004, Reata completed a license agreement with these organizations, and was granted exclusive worldwide rights to this new class of anticancer compounds. In 2008, orphan drug designation was assigned by the FDA for the treatment of pancreatic cancer. In 2010, the compound was licensed to Kyowa Hakko Kirin by Reata Pharmaceuticals in China, Japan, Korea, Thailand and Southeast Asian countries for the treatment of chronic kidney disease. Abbott acquired rights to develop and commercialize the drug outside US, excluding certain Asian markets.

Phase 1

Bardoxolone methyl was first advanced into the clinic to assess its anticancer properties. In two Phase 1 trials that included 81 oncology patients, bardoxolone methyl reduced serum creatinine levels, with a corresponding improvement in estimated glomerular filtration rate (eGFR). Improvements were more pronounced in a subset of patients with established CKD and were maintained over time in patients who continued on bardoxolone methyl therapy for 5 months. Based on these observed effects and the well-described role of oxidative stress and inflammation in CKD, especially in type 2 diabetes, it was hypothesized that bardoxolone methyl could improve renal function in CKD patients with type 2 diabetes.^[5]

Phase 2

A multi-center, double-blind, placebo-controlled Phase 2b clinical trial (BEAM) conducted in the US studied 227 patients with moderate to severe CKD (eGFR 20 – 45 ml/min/1.73m²) and type 2 diabetes. The primary endpoint was change in estimated GFR following 24 weeks of treatment. Following 24 weeks, patients treated with bardoxolone methyl experienced a mean increase in estimated GFR of over 10 ml/min/1.73m², compared with no change in the placebo group. Approximately three-quarters of bardoxolone methyl treated patients experienced an improvement in eGFR of 10 percent or more, including one-quarter who saw a significant improvement of 50% or more compared to less than 2% of patients on placebo. Adverse events were generally manageable and mild to moderate in severity. The most frequently reported adverse event in the bardoxolone methyl group was muscle spasm. Final data was published in The New England Journal of Medicine.

Concerns have been raised whether there is a true improvement in kidney function because of the significant weight loss of the patients in the active-treatment-group that ranged from 7.7-10.1 kg (7-10% of the initial body weight) and whether this weight loss in patients receiving bardoxolone included muscle wasting with a commensurate decrease in the serum creatinine level. In that case the decrease in creatinine would not necessarily be a true improvement in kidney function.^{[6][7][8][9][10]}

Phase 3

A multinational, double-blind, placebo-controlled Phase 3 outcomes study (BEACON) was started in June 2011, testing bardoxolone methyl’s impact on progression to ESRD or cardiovascular death in 1600 patients with Stage 4 CKD (eGFR 15 – 30 ml/min/1.73m²) and type 2 diabetes. This phase 3 trail was halted in October 2012 because of adverse effects (namely a higher cardiovascular mortality in the treatment arm).^[11]

Mechanism of action

Bardoxolone methyl is an inducer of the KEAP1–Nrf2 pathway.

PAPER

http://modernsteroid.blogspot.com/2012/04/synthetic-oleane-triterpenoids-as.html

Click to access ol400399x_si_001.pdf

1. To a stirred solution of oleanolic acid (22.8 grams, 0.05 mol, 1.0 equiv) in dimethyl formamide (200 mL) was
added powdered K2CO3 (20.7 grams, 0.15 mol, 3.0 equiv) slowly upon stirring, and the reaction mixture was allowed to
cool to 0 o
C. To the stirred suspension was added iodomethane (3.4 mL, 0.055 mol, 1.1 equiv) slowly, and after the
completion of addition, the reaction was allowed to warm to room temperature overnight. After the completion of the
reaction, dimethyl formamide was removed by distillation. The resulting solid mixture was dissolved in methylene
chloride (1 L) and washed with water (4 x 100 mL) and brine (1 x 100 mL). The organics was dried over Na2SO4 and the
solvent was removed to give the crude product 8 as a white solid, which was used directly for the next step without
further purifications.
2. To a stirred suspension of ester 8 (11.8 grams, 0.025 mol, 1.0 equiv) obtained above in anhydrous dimethyl
sulfoxide (250 mL) was added iodoxybenzoic acid (21.0 grams, 0.075 mol, 3.0 equiv) and fluorobenzene (5 mL). The
resulting suspension was heated to 85 o
C under nitrogen for 24 hours. After the completion of the reaction, it was
quenched with 20% aqueous sodium thiosulfate (200 mL). The resulting mixture was extracted with methylene chloride
(4 x 150 mL), the combined organic extracts were washed with saturated NaHCO3 (100 mL) and brine (100 mL), and
dried over Na2SO4. The solvent was removed to give the crude product 14 as yellowish solid, which was used directly for
the next step without further purifications.
3. To a stirred solution of 14 (9.32 grams, 0.02 mol, 1.0 equiv) in methylene chloride (100 mL) was slowly added mchloroperbenzoic
acid (6.4 grams, ~70% purity, 0.026 mol, 1.3 equiv) at 0 o
C. After the completion of addition, the
reaction was allowed to warm to room temperature and kept stirring for 24 hours. After the completion of the reaction,
the reaction mixture was diluted with methylene chloride (300 mL), and the resulting mixture was washed with 20%
aqueous sodium thiosulfate (3 x 100 mL), 10% potassium carbonate (2 x 100 mL), and brine (100 mL). The organics were
dried over Na2SO4 and the solvent was removed to give crude mixture of 15 and 16 as yellowish solid, which was used
directly for the next step without purifications.
4. To the resulting solution of 15 and 16 obtained above in acetic acid (50 mL) was added dropwise hydrobromic
acid (1.0 mL, 0.009 mol, 0.44 equiv) at room temperature. The reaction mixture was then heated to 35 o
C, and bromine
(5.8 mL, 0.05 mol, 2.4 equiv) was thus added dropwise. The resulting reaction mixture was kept stirring for another 24 h.
After completion of the reaction, the acid was removed under vacuum. And the residue was then quenched with 20%
aqueous sodium thiosulfate (100 mL), and extracted with methylene chloride (4 x 100 mL). The combined organic
extracts were washed with saturated sodium bicarbonate (2 x 50 mL), brine (1 x 50 mL), and dried over Na2SO4. The
solvent was removed to give crude bromo enone 17 as yellowish to yellow solid, which can be used directly for the next
step without further purification or subjected to flash column chromatography to give pure bromo enone 17 as a
yellowish solid.
5. To a stirred solution of bromo enone 17 (5.8 grams, 10.0 mmol, 1.0 equiv) in anhydrous dimethyl formamide (80
mL) was added copper (I) cyanide (1.0 grams, 11.0 mmol, 1.1 equiv) and potassium iodide (328 mg, 2.0 mmol, 0.20
equiv), and the resulting reaction mixture was heated to 120 o
C for 24 h. After the completion of reaction, it was cooled
to room temperature, quenched with water (200 mL), and diluted with ethyl acetate (500 mL). The organic phase was
washed with saturated NaHCO3 (2 x 80 mL), brine (80 mL), and dried over Na2SO4. Removal of solvent and flash column
chromatography over silica gel using hexanes:EtOAc (2:1) to give bardoxolone methyl (1) as a yellowish solid.

After the completion of the reaction, it was cooled to room temperature and
quenched with 20% aqueous sodium thiosulfate (20 mL). It was extracted with methylene chloride (3 x 20 mL), the
combined organic extracts were washed with saturated aqueous NaHCO3 (10 mL), brine (10 mL), and dried over Na2SO4.
Removal of solvent and flash column chromatography over silica gel using hexanes:EtOAc (4:1 & 2:1) to give iodo enone
18 (509 mg, 84%) as a yellowish solid. 1H NMR (500 MHz, CDCl3) δ 8.12 (s, 1H), 6.00 (s, 1H), 3.70 (s, 3H), 3.04 (dd, 1H, J1 =
10.0 Hz, J2 = 3.7 Hz), 2.92 (d, 1H, J = 4.6 Hz), 1.63-1.94 (m, 9H), 1.46-1.62 (m, 3H), 1.43 (s, 3H), 1.18-1.36 (m, 3H), 1.30 (s,
3H), 1.23 (s, 3H), 1.17 (s, 3H), 1.02 (s, 3H), 1.00 (s, 3H), 0.90 (s, 3H); 13C NMR (500 MHz, CDCl3) δ 199.6, 196.9, 178.4,
170.3, 163.5, 124.1, 102.3, 52.1, 49.9, 48.4, 47.4, 46.4, 45.9, 45.4, 42.3, 36.0, 34.7, 33.5, 33.0, 32.1, 31.7, 30.9, 28.3, 28.2,
27.3, 24.8, 23.3, 22.9, 22.4, 21.9, 18.8; FT-IR (solution, CDCl3, cm-1): 2952, 2869, 2253, 1717, 1659, 1469, 1386, 907, 732,
651, 623, 443; HRMS-ESI (calcd. for C31H44IO4 [M+H]+
) 607.2284, found 607.2280.

CLIP

PATENT

WO1999065478A1

In a preferred embodiment, such compounds include derivatives of ursolic acid and oleanoic acid. In a particularly preferred embodiment, derivatives of OA, e.g., 2-cyano-3,12-dioxoolean-l,9-dien-28oic acid (CDDO):

have been found to be effective in suppression of human breast cancer cell growth, and highly potent in many vitro assay systems such as: suppression of nitric oxide and prostaglandin production in macrophages, inhibition of growth of human breast cancer cells, suppression of nitric oxide formation in rat prostate cells, and suppression of prostaglandin formation in human colon fibroblasts, as detailed in the Figures.

Compounds were synthesized as below:

Scheme 1

Scheme 2

a: HCO₂Et/MeONa/THF,b: PhSeCl/AcOEt; 30%H₂0₂/THF,c: NH₂OH-HCI EtOH/H₂O, d: MeONa/MeOH/Et₂O,e: KOH/MeOH,f: Jones,g:HCO₂Et/MeONa/PhH,h: Lil/DMF Compound 10 was prepared by formylation of OA (Compound 9) (Simonsen and Ross, 1957) with ethyl formate in the presence of sodium methoxide in THF (Clinton et al., 1961). Compound 7 was obtained by introduction of a double bond at C-l of Compound 10 with phenylselenenyl chloride in ethyl acetate and sequential addition of 30%) hydrogen peroxide (Sharpless et al, 1973). Compound 11 was synthesized from Compound 10 by addition of hydroxylamine in aqueous ethanol; cleavage of Compound 11 with sodium methoxide gave Compound 12 (Johnson and Shelberg, 1945). Compound 14 was prepared from Compound 13 (Picard et al, 1939) by alkali hydrolysis followed by Jones oxidation. Compound 15 was prepared by formylation of Compound 14 with ethyl formate in the presence of sodium methoxide in benzene. Compound 16 was synthesized from Compound 15 by addition of hydroxylamine. Cleavage of 16 with sodium methoxide gave Compound 17. Compound 6 (CDDO) was prepared by introduction of a double bond at C-l of Compound 17 with phenylselenenyl chloride in ethyl acetate and sequential addition of 30% hydrogen peroxide, followed by halogenolysis with lithium iodide in DMF (Dean, P.D.G., 1965).

PATENT

WO2009/146216 A2,

Compounds 401, 402, 404, 402-04, 402-35 and 402-56 can be prepared according to the methods taught by Honda et al. (1998), Honda et al. (2000b), Honda et al. (2002), Yates et al. (2007), and U.S. Patent 6,974,801, which are all incorporated herein by reference. The synthesis of the other compounds are disclosed in the following applications, each of which is incorporated herein by reference: U.S. Application Nos. 61/046,332, 61/046,342, 61/046,363, 61/046,366, 61/111,333, 61/111,269, and 61/111,294. The synthesis of the other compounds are also disclosed in the following separate applications filed concurrently herewith, each of which is incorporated herein by reference in their entireties: U.S. Patent Application by Eric Anderson, Xin Jiang, Xiaofeng Liu; Melean Visnick, entitled “Antioxidant Inflammation Modulators: Oleanolic Acid Derivatives With Saturation in the C- Ring,” filed April 20, 2009; U.S. Patent Application by Eric Anderson, Xin Jiang and Melean Visnick, entitled “Antioxidant Inflammation Modulators: Oleanolic Acid Derivatives with Amino and Other Modifications At C-17,” filed April 20, 2009; U.S. Patent Application by Xin Jiang, Xioafeng Liu, Jack Greiner, Stephen S. Szucs, Melean Visnick entitled, “Antioxidant Inflammation Modulators: C-17 Homologated Oleanolic Acid Derivatives,” filed April 20, 2009.

PAPER

Chemical Communications, 2011 ,  vol. 47,   33  p. 9495 – 9497

http://pubs.rsc.org/en/Content/ArticleLanding/2011/CC/c1cc11633a#!divAbstract

http://www.rsc.org/suppdata/cc/c1/c1cc11633a/c1cc11633a.pdf NMR GIVEN

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO)
A mixture of 1 (0.25 g, 0.51 mmol) and DDQ (0.12 g, 0.51 mmol) in anhydrous benzene (20 mL) was
refluxed for 15 min. After filtration, the filtrate was evaporated in vacuo to give a residue, which was
subjected to flash column chromatography (petroleum ether/EtOAc) to give CDDO as an amorphous
solid (0.23 g, 91%). The title compound was known as CAS 218600-44-3

m.p. 180-182 °C;
ESI-MS: 490 [M-H]-, 492 [M+H]+;

1H NMR (300M Hz, CDCl3, 25 °C, TMS): δ 8.05 (1H, s), 5.99 (1H, s), 3.03-2.98 (2H, m), 1.55,1.38,
1.34, 1.22, 1.00, 0.91, 0.85 (each 3H,s ,CH3) ppm.

PAPER

SYNTHESIS

Journal of Medicinal Chemistry, 2000 ,  vol. 43,   22  p. 4233 – 4246

http://pubs.acs.org/doi/full/10.1021/jm0002230

Bioorganic and Medicinal Chemistry Letters, 1998 ,  vol. 8,   19  p. 2711 – 2714

http://www.sciencedirect.com/science/article/pii/S0960894X9800479X

PAPER

Bioorganic and Medicinal Chemistry Letters, 2005 ,  vol. 15,  # 9  p. 2215 – 2219

http://www.sciencedirect.com/science/article/pii/S0960894X05003306

PATENT

WO2002047611A2

Method of synthesis of CDDO. CDDO may be synthesized by the scheme outlined below.

Methyl-CDDO. Methyl-CDDO (CDDO-Me), the C-28 methyl ester of CDDO, also exerts strong antiproliferative and apoptotic effects on leukemic cell lines and in primary AML samples in vitro as well as induces monocytic differentiation of leukemic cell lines and some primary AMLs. Thus, CDDO-Me provides chemotherapy for the treatment of leukemias. The present invention demonstrates that this effect is profoundly increased by combination of CDDO-Me with other chemotherapeutic agents. These include retinoids such as ATRA, 9-cis retinoic acid, , LG100268, LGD1069 (Targretin, bexarotene), fenretinide [N-(4- hydroxyphenyl)retinamide, 4-HPR], CD437 and other RXR and RAR-specific ligands. This combination also increases ara-C cytotoxicity, further reduces AML colony formation, inhibits ERK phosphorylation and promotes Bcl-2 dephosphorylation, and inhibits in vitro angiogenesis. The ability of CDDO-Me in combination with retinoids to induce differentiation in leukemic cells in vitro show that these compounds may have similar in vivo effects. The anti-angiogenic properties of CDDO-Me further increase its potent anti-leukemia activity in combination with retinoids. Furthermore, CDDO-Me was found to be more potent at lower concentrations than CDDO.

Method of synthesis of CDDO-Me.

CDDO-Me may be synthesized by the scheme outlined below.

The present invention provides combinations of CDDO-compounds and chemotherapeutic agents that are useful as treatments for cancers and hematological malignancies. In one embodiment, the chemotherapeutics are retinoids. As CDDO- compounds are PPARγ ligands and PPARγ is known to be altered in many types of cancers, the inventors contemplate, that ligation of PPARγ in combination with retinoids such as, RXR-specific ligands, provides a mechanistic basis for maximal increase in transcriptional activity of the target genes that control apoptosis and differentiation. The CDDO-compounds and retinoids in combination demonstrate an increased ability to induce differentiation, induce cytotoxicity, induce apoptosis, induce cell killing, reduce colony formation and inhibit the growth of several types of leukemic cells.

PAPER

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.

References

• Reata Pharmaceuticals, Inc. – bardoxolone methyl
• Bardoxolone Methyl and Kidney Function in CKD with Type 2 Diabetes
• Effect of Bardoxolone Methyl on Kidney Function in Patients with T2D and Stage 3b – 4 CKD
• American Diabetes Association presentation

Professor Honda received his B.S. degree in Chemistry in 1974, his M.S. degree in Organic Chemistry in 1976, and his Ph.D. in Organic Chemistry in 1979 from the University of Tokyo. In 1979, he joined the Department of Drug Discovery Chemistry at Suntory Institute for Biomedical Research in Japan and worked there as a drug synthetic chemist (finally senior researcher) for 13 years. In 1991, he joined the Central Pharmaceutical Research Institute at Japan Tobacco Inc. and worked as a chief senior researcher for 3 years. In 1995, he joined Dr. Gribble’s laboratory at Dartmouth College as a research associate. In 1998, he joined the research faculty of Dartmouth College. In 2005, he was promoted to Research Associate Professor. http://www.dartmouth.edu/~chem/faculty/th.html

Dr. Honda and his collaborators have further explored new structures based on CDDO and different five-ringed triterpenoids.

During the course of these investigations, Dr. Honda has designed three-ringed compounds with similar enone functionalities in rings A and C to those of CDDO, but having a much simpler structure than five-ringed triterpenoids. He and his collaborators have found that they are also a novel class of potent anti-inflammatory, cytoprotective, growth suppressive, and pro-apoptotic compounds. Amongst such three-ringed compounds, TBE-31 with the C-8a ethynyl group is much more potent than CDDO in various bioassays in vitro and in vivo. Thus, further investigation (design, synthesis, biological evaluation, etc.) of new TBE-31 analogues is currently being performed in order to discover analogues having different and/or better features than TBE-31, for example, higher potency and lower toxicity, better bioavailability and different distributions in organs, high water-solubility and so on.

Mechanism studies suggest that CDDO regulates various molecules regarding inflammation, differentiation, apoptosis, and proliferation by reversible Michael addition between the cyano enone functionality of CDDO and the sulfhydryl groups of cysteine moieties on these molecules. Based on this fact and the structure of TBE-31, Dr. Honda has designed single-ringed compounds, which represent the ideal simple structure. The synthesis of these new compounds is currently in progress.

Bardoxolone methyl

Clinical data
Routes of administration	Oral
ATC code	none
Legal status
Legal status	Investigational
Identifiers
IUPAC name[show]
CAS Number	218600-53-4
PubChem CID	400769
IUPHAR/BPS	3443
ChemSpider	355161
ChEMBL	CHEMBL1762621
ECHA InfoCard	100.132.153
Chemical and physical data
Formula	C32H43NO4
Molar mass	505.69 g/mol
3D model (JSmol)	Interactive image
SMILES

///////////////Bardoxolone Methyl, CDDO-Me; CDDO methyl ester; 218600-53-4; Bardoxolone (methyl); RTA 402 CDDO-Me, CDDO methyl ester, 218600-53-4, Bardoxolone (methyl), RTA 402 , PHASE 3,NSC 713200

CC1(CCC2(CCC3(C(C2C1)C(=O)C=C4C3(CCC5C4(C=C(C(=O)C5(C)C)C#N)C)C)C)C(=O)OC)C