Fudapirine

It's only fair to share...

Fudapirine

CAS 1859978-72-5

MFC34H33ClN2O2 MW537.1 g/mol

(1R,2S)-1-[5-(4-chlorophenyl)-2-methoxy-3-pyridinyl]-4-(dimethylamino)-2-naphthalen-1-yl-1-phenylbutan-2-ol

(1R,2S)-1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol
antibacterial, Sudapyridine, WX-081, WX 081, 7X86XPE5TG,

A Phase III Study of Oral Sudapyridine (WX-081) Tablets in Rifampicin-Resistant Pulmonary Tuberculosis PatientsCTID: NCT05824871Phase: Phase 3Status: RecruitingDate: 2025-06-29
Drug-Drug Interaction and Food Effect of Sudapyridine(WX-081) With Itraconazole and Rifampin in Healthy Chinese AdultsCTID: NCT06701136Phase: Phase 1Status: Not yet recruitingDate: 2025-02-12
Sudapyridine (WX-081) in Healthy VolunteersCTID: NCT06117514Phase: Phase 1Status: CompletedDate: 2023-11-07
Evaluation of Early Bactericidal Activity and Safety in Pulmonary Tuberculosis With WX-081CTID: NCT04608955Phase: Phase 2Status: CompletedDate: 2023-09-11

Fudapirine (also known as sudapyridine or WX-081) is a novel, next-generation antimycobacterial drug primarily being developed to treat tuberculosis (TB). It belongs to a chemical class called diarylquinolines, making it a close analogue of bedaquiline, an already established drug used for drug-resistant tuberculosis.Key Facts About FudapirinePrimary Function: It displays powerful anti-mycobacterial activity against Mycobacterium tuberculosis strains.

Mechanism: As a diarylquinoline, it selectively inhibits bacterial ATP synthase, effectively cutting off the energy supply that the tuberculosis bacteria need to survive and replicate.Development Stage: According to pharmacology databases like the IUPHAR/BPS Guide to PHARMACOLOGY, the drug has advanced into Phase III clinical evaluation.Official Naming: While initially designated as WX-081, the World Health Organization (WHO) assigned it the International Nonproprietary Name (INN) fudapirine in early 2025.Other Applications: Beyond standard TB, researchers are investigating its therapeutic potential against non-tuberculous mycobacterial (NTM) infections.

PAT

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=6D72E4125E9DD99079BEE19ECCE38CED.wapp2nC?docId=WO2017121323&_cid=P22-MPT687-41395-1

Step 5:
Synthesis of
1-(5-(4-chlorophenyl)-2-methoxypyridin-3-yl)-4-(dimethylamino)-2-(naphth-1-yl)-1-phenylbut-2-ol

Titration of n-butyllithium : Under nitrogen protection, 1.00 g

of diphenylacetic acid (Alfa, 4.71 mmol) was added to 10 mL of tetrahydrofuran to form a colorless and transparent solution. A hexane solution of

n-butyllithium was slowly added dropwise to this solution using a syringe. The solution was observed to turn yellow locally during the addition, but the yellow color quickly disappeared. The endpoint was reached when a yellow solution formed after one drop and did not fade within half a minute. The volumes of

n-butyllithium were recorded (1.927 mL and 1.985 mL, with an average volume of 1.95 mL). Therefore, the concentration of

the n-butyllithium hexane solution used was 2.42 mol/L.

[0171]TMP (2.74 kg, 19.3 mol) was dissolved in anhydrous tetrahydrofuran (12 L). The reaction temperature was cooled to -65°C using a dry ice-acetone bath, and then

n-butyllithium (8 L, 19.3 mol, 2.42 mol/L n-hexane solution) was added dropwise. The temperature was controlled between -20°C and -78°C. The reaction system was observed to gradually change color from light yellow to red to deep red, eventually forming a yellow suspension. Stirring was continued at this temperature for 30 minutes. Then, the reaction temperature was lowered to -75°C to -80°C, and over 4–6 hours, a solution of

3-benzyl-5-(4-chlorophenyl)-2-methoxypyridine (4.08 kg, 12.9 mol) in anhydrous tetrahydrofuran (6 L) was slowly added dropwise. The temperature was maintained between -65°C and -78°C, and a mild exothermic reaction with a deep red color was observed. After the initial addition was complete, a solution of 3-(dimethylamino)-1-(naphth-1-yl)propyl-1-one (3.26 kg, 12.9 mol, 90% purity) in anhydrous tetrahydrofuran (2.0 L) was slowly added dropwise over 2–4 hours. The system exhibited significant exothermic activity, and the flow rate was controlled to maintain the temperature at -65°C to -78°C. After the addition was complete, the temperature was maintained at -65°C to -78°C, and stirring was continued for another half hour. HPLC analysis showed that the content of

3-benzyl-5-(4-chlorophenyl)-2-methoxypyridine was less than 10%. The reaction solution was slowly added to a saturated

ammonium chloride solution (40 L) for quenching, and the mixture was separated. The aqueous phase was extracted with ethyl acetate (30 L). The combined organic phases were washed and separated with saturated brine (30 L). The organic phases were concentrated under reduced pressure at 40–50 °C to obtain a yellow oily crude product (13.5 kg). The crude product was stirred in a mixed solvent of ethyl acetate/n-heptane (4 L, 1/4) at 5–15 °C for 16 hours to precipitate a white solid. The product was filtered, and the filter cake was slurried with ethanol (4 L × 2). After filtration, the filter cake was vacuum dried to constant weight (50 °C, 24–48 hours) to obtain the target compound 1-(5-(4-chlorophenyl)-2-methoxypyridin-3-yl)-4-(dimethylamino)-2-(naphth-1-yl)-1-phenylbut-2-ol (1.83 kg, yield 23.23%), a white solid. HPLC identification showed that isomer A accounted for 88.3% and isomer B accounted for 4.8%.

¹ H NMR (400MHz, CDCl ₃ )δ: 8.85(d,J＝2.3Hz,1H),8.64(d,J＝8.7Hz,1H),8.32(d,J＝2.4Hz,1H),7. 98-7.86(m,2H),7.72-7.61(m,2H),7.57(d,J＝8.4Hz,2H),7.54-7.43(m,3 H),7.33(t,J＝7.8Hz,1H),7.20-7.17(m,2H),6.95-6.87(m,3H),5.85(s,1 H),4.17(s,3H),2.60-2.51(m,1H),2.19-2.04(m,2H),2.01-1.97(m,7H).

[0172]Step 6: Synthesis of (1R,2S)-1-(5-(4-chlorophenyl)-2-methoxypyridin-3-yl)-4-(dimethylamino)-2-(naphth-1-yl)-1-phenylbut-2-ol compound I-2

Method 1:

[0175]Two parallel batches were prepared: R-(-)-binaphthol phosphate (519.3 g, 1.49 mol) was suspended in DMSO (1.0 L) and heated to 50 °C with stirring until dissolved and clear. 1-(5-(4-chlorophenyl)-2-methoxypyridin-3-yl)-4-(dimethylamino)-2-(naphthaleneethanol-1-yl)-1-phenylbutyl-2-ol (910 g, 1.49 mol, isomer A content 88.3%) was added to an ethanol (24 L) solution, and the DMSO (1.0 L) solution of R-(-)-binaphthol phosphate prepared above was added dropwise over 1–2 hours with stirring (196 rpm). Undissolved particulate compounds began to dissolve, but a more viscous emulsion formed. After the addition was complete, the reaction mixture was stirred at 15–35 °C for 16 hours. The reaction solution was heated to reflux in an oil bath and refluxed for 1 hour. Heating was then stopped, and the reaction solution was cooled to 15–35°C and stirred for 16 hours. The reaction solution was filtered (two batches were combined for processing). Due to the high viscosity of the solids, filtration was slow. The filter cake was slurried three times with ethanol (20 liters). The combined organic phases were concentrated to constant weight to obtain a yellow oily substance (5 kg). Water (10 liters) and ethyl acetate (5 liters) were added to this crude product. The pH of the system was adjusted to 11 with a 10% cold

sodium hydroxide aqueous solution, and stirring was continued for 1 hour. Then, the mixture was separated. A large amount of solid precipitated from the system. The solid obtained by filtration was isomer A (350 g, purity 97%, white solid). The filtrate was concentrated under reduced pressure at 50°C to constant weight, and ethanol (1.0 L) was added. The mixture was stirred at 15-35°C for 16 hours, filtered, and the filter cake was washed three times with ethanol (400 mL) to obtain a white solid. The solid was dried under vacuum to constant weight (50°C, 24-48 hours) to obtain compound I-2 (400 g, purity 95%, ee value greater than 99.5%, yield 24%), a white solid.

¹ H NMR (400MHz, CDCl

₃ )δ: 8.85(d,J＝2.3Hz,1H),8.64(d,J＝8.7Hz,1H),8.32(d,J＝2.4Hz,1H),7. 98-7.86(m,2H),7.72-7.61(m,2H),7.57(d,J＝8.4Hz,2H),7.54-7.43(m,3 H),7.33(t,J＝7.8Hz,1H),7.20-7.17(m,2H),6.95-6.87(m,3H),5.85(s,1 H),4.17(s,3H),2.60-2.51(m,1H),2.19-2.04(m,2H),2.01-1.97(m,7H).

ANAX LABORATORIES

WEBSITE https://www.anaxlab.com/

Discovery Solutions, Supporting the chemistry needs of clients in the Medical, Analytical and Bio Sciences

Development Solutions, Developing from Lab scale to PR&D, Kilo Scale-ups and Commercial Scales

SEE MORE………Integrated Solutions, Manufacturing Solutions, Products,
Can’t Find? Let’s Connect