Tuesday, 25 August 2026

Prifetrastat

 

Prifetrastat

CAS 2569008-99-5

MFC19H18N4O5S MW414.4 g/mol

N-(6-((1H-Pyrazol-1-yl)methyl)-4-methoxybenzo[d]isoxazol-3-yl)-2-methoxybenzenesulfonamide

2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide
antineoplastic, PF-07248144, PF 07248144, Solid tumours, CANCER, KAT6-IN-1, GN6DU4ZE30

Prifetrastat is an inhibitor of MYST histone acetyltransferase (HAT) KAT6, with potential antineoplastic activity. Upon administration, prifetrastat targets and binds to KAT6, and inhibits the acetylation of histones and other nonhistone substrates. This may disrupt gene expression and inhibit the proliferation of tumors that overexpress KAT6. KAT6A (MOZ; MYST3) and KAT6B (MORF; MOZ2; MYST4), commonly amplified genes in solid tumors, play key roles in cell cycle regulation and in tumorigenesis.

Prifetrastat (also known as PF-07248144) is an investigational, first-in-class small molecule drug that acts as a selective inhibitor of the epigenetic modifiers KAT6A and KAT6B. It is primarily studied as an antineoplastic agent for hormone receptor-positive (ER+/HER2–) advanced or metastatic breast cancer.

Mechanism of Action

  • Inhibits KAT6A and KAT6B histone acetyltransferases to block abnormal tumor cell growth.
  • Suppresses lineage-specific gene expression tied to estrogen receptor signaling and drug resistance.
  • Induces cell cycle arrest and tumor senescence.

Clinical Development

  • Evaluated in clinical trials (such as phase 1/2 and phase 3 evaluations) for patients whose breast cancer progressed after prior endocrine therapy and CDK4/6 inhibitors.
  • Commonly tested in combination regimens alongside anti-estrogen therapies like fulvestrant

Prifetrastat (also known as PF-07248144) is an investigational, first-in-class small molecule drug that acts as a selective inhibitor of the epigenetic modifiers KAT6A and KAT6B. It is primarily studied as an antineoplastic agent for hormone receptor-positive (ER+/HER2–) advanced or metastatic breast cancer.

Mechanism of Action

  • Inhibits KAT6A and KAT6B histone acetyltransferases to block abnormal tumor cell growth.
  • Suppresses lineage-specific gene expression tied to estrogen receptor signaling and drug resistance.
  • Induces cell cycle arrest and tumor senescence.

Clinical Development

  • Evaluated in clinical trials (such as phase 1/2 and phase 3 evaluations) for patients whose breast cancer progressed after prior endocrine therapy and CDK4/6 inhibitors.
  • Commonly tested in combination regimens alongside anti-estrogen therapies like fulvestrant
  • Phase IIIHER2 negative breast cancer
  • Phase IISolid tumours
  • No development reportedBreast cancer
  • 07 Aug 2026Prifetrastat is still in phase II development in Solid-tumours (Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater) in USA, Australia, Japan, China, South Korea (PO, Tablet) (NCT04606446)
  • 07 Aug 2026Prifetrastat is still in phase II development in Solid-tumours (Monotherapy, Late-stage disease, Metastatic disease, Second-line therapy or greater) in USA, Australia, Japan, China, South Korea (PO, Tablet) (NCT04606446)
  • 28 Jul 2026No recent reports of development identified for phase-I development in Breast-cancer(Metastatic disease) in USA (PO)

PAT

[WO2020254946]

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020254946&_cid=P12-MSO1IP-41527-1

Example 45: Preparation of 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide according to Scheme C (Route A).

To a suspension of 4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-amine (A-2) (2.5 g, 10 mmol) in pyridine (8.0 mL) was added 2-methoxybenzene-1-sulfonyl chloride (3.17 g, 15.4 mmol). The reaction was stirred at 120 °C for 1.5 h. The mixture was cooled to room temperature and diluted with MeOH. The resulting suspension was filtered. and the filter cake was washed with MeOH (30 mL). The solids were dissolved in DCM (50 mL) and MeOH (30 mL) was added. The DCM was removed under vacuum

and the precipitate was collected by filtration. The filter cake was dried by lyophilization to provide 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide (Example 45) (2.5 g, 59% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) d 10.18 (s, 1H), 7.87 (d, J= 2.0 Hz, 1H), 7.80 (dd, J=1.6, 7.9 Hz, 1H), 7.66– 7.59 (m, 1H), 7.49 (d, J=1.5 Hz, 1H), 7.19 (d, J=8.3 Hz, 1H), 7.09 (t, J=7.7 Hz, 1H), 6.83 (s, 1H), 6.74 (s, 1H), 6.30 (t, J=2.0 Hz, 1H), 5.44 (s, 2H), 3.82 (s, 3H), 3.78 (s, 3H); m/z (ESI+) 415.0 (M+H) + .

Example 45: Alternative preparation of 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide according to Scheme D.

A 100 mL reactor equipped with an overhead stirrer was charged with 4-methoxy-6-(1H-pyrazol-1-ylmethyl)-1,2-benzoxazol-3-amine (A-2) (10.00 g, 40.94 mmol), 2-methoxybenzenesulfonyl chloride (10.15 g, 49.13 mmol), and acetonitrile (100 mL). The resulting suspension was stirred at 25 °C for 55 minutes. Via pipette, dimethylsulfoxide (0.36 mL, 4.09 mmol) was added in one portion. Via syringe, 3,5-lutidine (14.8 mL, 122.82 mmol) was added dropwise over 15 minutes. The resulting light-yellow suspension was stirred at 25 °C for 18 hours to reach >98% conversion as judged by LCMS. The reaction mixture was acidified with 1 M aq. HCl (100 mL), then

concentrated to ~80 mL (rotary evaporator, 40 °C, 85 mbar). The slurry was treated with additional 1 M aq. HCl (40 mL) to rinse down the walls of the vessel, then stirred at 20 °C for 2.5 hours. The resulting precipitate was collected by suction filtration. The filter cake was washed with water (2 x 50 mL), then dried under vacuum at 35 °C for 48 hours, affording crude 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide (Example 45) (15.2 g, 90% yield, 98% purity by LCMS) as a solid. m/z 415.1 (M+H) + .

To purify the crude product, a suspension of crude 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide (Example 45) (14.00 g, 33.78 mmol) in dichloromethane (210 mL) was heated in a 40 °C bath until a clear solution was obtained (10 minutes). The mixture was filtered, and the filtrate returned to a clean reaction vessel, using additional dichloromethane (70 mL) to quantitate the transfer. Ethyl acetate (140 mL) was added to the solution over 2 minutes, then the mixture stirred for 2.5 hours. No crystallization was observed, so the solution was concentrated under reduced pressure (200 mbar) to remove dichloromethane (volume was reduced by about 70 mL). More ethyl acetate (140 mL) was added to the residue, and the mixture stirred at room temperature for 21 hours. The resulting suspension was concentrated under reduced pressure (40 °C, 200 mbar) to about 280 mL, then stirred at room temperature for 3 hours. The solids were collected by filtration, with additional ethyl acetate (70 mL) used to rinse the reaction vessel and filter cake. The filter cake was dried in a vacuum oven at 35 °C for 23 hours, affording 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide (Example 45) (12.0 g, 85% yield, 97.9% purity by UPLC, no single impurity larger than 0.5%) as a solid. m/z 415.1 (M+H) + .

To purify further, a suspension of 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide (Example 45) (2.0 g, 4.73 mmol) in acetone (80 mL) was heated to reflux (bath temperature 55 °C) with stirring for 2 hours. While the mixture was still heated, ethyl acetate (30 mL) was added slowly, so that the internal temperature remained above 45 °C. The resulting slurry was concentrated to about 30 mL under mild vacuum (bath temp 65 °C), then cooled slowly at a rate of 1 °C/min to 20 °C (~31 minutes). The resulting precipitate was collected by suction filtration. The filter cake dried under vacuum at 50 °C for 22 hours, yielding 2-methoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide (Example 45) (1.825 g, 93% yield, 99.5% purity by UPLC) as a crystalline solid. 1 hour

NMR (400 MHz, CHLOROFORM-d) d 8.14 (dd, J=1.7, 7.8 Hz, 1H), 8.04 (s, 1H), 7.59 -7.51 (m, 2H), 7.44 (d, J=2.2 Hz, 1H), 7.14 - 7.06 (m, 1H), 6.95 (d, J=8.3 Hz, 1H), 6.78 (d, J=0.6 Hz, 1H), 6.45 (s, 1H), 6.32 (t, J=2.1 Hz, 1H), 5.38 (s, 2H), 3.97 (s, 3H), 3.91 (s, 3H).

PAT

US20250122182, Example 45,

PAT

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=EB10EA12C4409E47C6165613EF765C49.wapp1nC?docId=WO2026003716&_cid=P12-MSO1HW-40533-1

Scheme 1

Step 2

In an inerted reactor were added 6-((1 H-pyrazol-1-yl)methyl)-4-methoxybenzo[d]isoxazol-3-amine (lnt-4, 27.5 Kg, 112.6 mol, 1 equiv.), 2-methoxybenzenesulfonyl chloride (lnt-5, 33.9 Kg, 168.9 mol, 1.5 equiv.) and THF (248 L, 9-L/Kg). A solution of sodium te/Y-butoxide in THF (2 M, 197 L, 394.1 mol, 3.5 eq.) was added to the stirred mixture at 20 °C over 4 h. At the end of the addition the line was rinsed with THF (27.5 L, 1 L/Kg) and the mixture stirred for a further 1 h. Following reaction completion water (413 L, 15 L/Kg) was added at once followed by slow addition of aq. HCI (2 M, 197 L, 394.1 mol, 3.5 equiv.). The mixture was left stirring overnight, then the slurry was filtered, washed twice with CH3OH (82.5 L, 3 L/Kg) and dried to afford the title compound as a white solid (42.32 Kg, 90.6% yield).

1H NMR (400 MHz, DMSO) 5 10.09 (s, 1 H), 7.87 (dd, J = 2.3, 0.7 Hz, 1 H), 7.81 (dd, J = 7.8, 1.7 Hz, 1 H), 7.63 (ddd, J = 8.4, 7.4, 1.7 Hz, 1 H), 7.50 (dd, J = 1.8, 0.7 Hz, 1 H), 7.10 (td, J = 7.6, 1 .0 Hz, 1 H), 6.84 (d, J = 1 .0 Hz, 1 H), 6.30 (t, J = 2.1 Hz, 1 H), 5.44 (s, 2H), 3.83 (s, 3H), 3.79 (s, 3H). 13C NMR (101 MHz, DMSO) 5 164.82, 156.92, 154.39, 151.76, 144.13, 139.80, 135.73, 131.03, 130.43, 127.66, 120.52, 113.34, 106.25, 106.17, 104.42, 101.33, 56.51, 56.42, 55.01. HRMS: Ci9Hi8N4O5S+ [M+1 ]+ calculated:

415.1072; measured: 415.1071.

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References

///////////prifetrastat, anax labs, antineoplastic, PF-07248144, PF 07248144, Solid tumours, CANCER, KAT6-IN-1, GN6DU4ZE30

#prifetrastat, #anax labs, #antineoplastic, #PF-07248144, #PF 07248144, #Solid tumours, #CANCER, #KAT6-IN-1, #GN6DU4ZE30

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Pruvonertinib

 

Pruvonertinib

CAS 2064269-82-3

MF C27H32N8O2 MW500.6 g/mol

N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(8-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide

N-(2-{2-(dimethylamino)ethylamino}-4-methoxy-5-{[4-(8-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)prop2-enamide
epidermal growth factor receptor tyrosine kinase inhibitor, antineoplastic, YK-029A, YK 029A, HXJ9459HFK

Pruvonertinib is an orally bioavailable, mutant-selective, third-generation epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, pruvonertinib targets, binds to and inhibits the activity of EGFR with exon 20 insertion (Ex20ins) activating mutations, the gatekeeper mutation T790M and some other rare mutations, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.

Pruvonertinib (also known by its development code YK-029A) is an investigational, orally bioavailable, mutant-selective, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Developed by Puhe Pharmaceutical, it is designed as an antineoplastic agent primarily targeting advanced non-small cell lung cancer (NSCLC) with specific resistant mutations.

Mechanism of Action

  • Target Specificity: Binds selectively to mutant forms of EGFR.
  • Resistance Targeting: Inhibits the gatekeeper T790M mutation and exon 20 insertion (Ex20ins) mutations.
  • Scaffold Lineage: Structurally derived as an analogue of the established oncology drug osimertinib.
  • Tumour Regression: Blockades downstream EGFR-mediated signaling to induce cell death and stunt tumor vascularization.

Clinical Development & Indications

  • Primary Indication: Treatment of advanced, metastatic, or biomarker-positive Non-Small Cell Lung Cancer (NSCLC).
  • Development Status: Pre-commercial asset undergoing active clinical trial screening and testing evaluations.
  • Regulatory Track: Listed under the World Health Organization (WHO) Proposed International Nonproprietary Names (INN) List 132.

SYN

Analogue 6

Discovery of YK-029A, a novel mutant EGFR inhibitor targeting both T790 M and exon 20 insertion mutations, as a treatment for NSCLC

Publication Name:European Journal of Medicinal Chemistry, Publication Date:2023-10-05

PMID:37406381DOI:10.1016/j.ejmech.2023.115590

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US298712718&_cid=P10-MSQW7F-15668-1

N-(2-methoxy-4-(N 1,N 2,N 2-trimethyl-1,2-ethylenediamine-1-yl)-5-acrylamidephenyl)-4-(8-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine (hereinafter referred to as “Compound 1”) is a novel EGFR inhibitor represented by Formula (I):

The above compound is described in Chinese Patent Application 201610679161.7, and the content of which can be used as a reference for the present application

Step 7: Preparation of Drug Substance H (i.e. Compound 1)

Intermediate F (1.01 kg, 2.26 mol) was added to a mixed solution of acetonitrile (4.73 kg) and water (1.52 kg), and the temperature was lowered to 0 to 5° C. 3-Chloropropionyl chloride (373 g, 2.94 mol) was added dropwise. After the addition, the mixture was stirred at 0˜5° C. for 0.5 h. The completion of the reaction was detected.
      An aqueous solution of sodium hydroxide (sodium hydroxide: 290 g, 7.24 mol; purified water: 505 g) was added dropwise, and the reaction was heated to 65˜75° C. and stirred for 2˜3 h. The completion of the reaction was detected. The reaction system was cooled to 25-35° C., and purified water (4040 g) was added dropwise. Seed crystals were added and the mixture was stirred for 1˜2 h. Purified water (6060 g) was added dropwise. After the addition, the temperature was lowered to 5-10° C., and the mixture was stirred for 1˜2 h and filtered. The filter cake was rinsed with a mixed solvent of acetonitrile (1.6 kg) and purified water (4 kg), and then dried to give 900 g of the drug substance H with a purity of 97.8%. Yield: 79%.
      LCMS, m/z (ES+)(M+H +) 501.2,
       1HNMR (400 MHz, d 6-DMSO) δ 10.11 (s, 1H), 9.67 (d, J=5.8 Hz, 1H), 8.64 (s, 1H), 8.57 (s, 1H), 8.53 (s, 1H), 8.35 (d, J=5.4 Hz, 1H), 7.32 (d, J=5.4 Hz, 1H), 7.24 (d, J=6.9 Hz, 1H), 7.06 (s, 1H), 6.80 (t, J=6.9 Hz, 1H), 6.41 (dd, J=16.9, 10.1 Hz, 1H), 6.18 (dd, J=16.9, 1.9 Hz, 1H), 5.73 (dd, J=10.1, 1.9 Hz, 1H), 3.79 (s, 3H), 2.91 (t, J=5.7 Hz, 2H), 2.75 (s, 3H), 2.54 (s, 3H), 2.34 (t, J=5.8 Hz, 2H), 2.21 (s, 6H).

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References

/////////pruvonertinib, anax labs, epidermal growth factor receptor tyrosine kinase inhibitor, antineoplastic, YK-029A, YK 029A, HXJ9459HFK

#pruvonertinib, #anax labs, #epidermal growth factor receptor tyrosine kinase inhibitor, #antineoplastic, #YK-029A, #YK 029A, #HXJ9459HFK

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Monday, 24 August 2026

Ralometostat

 

Ralometostat

CAS 2760481-53-4

MF C21H23N5O2S MW409.51

(2R,5S)-N-(6-Amino-5-methyl-3-pyridinyl)-2-(5-benzothiazolyl)-5-methyl-α-oxo-1-piperidineacetamide

1-Piperidineacetamide, N-(6-amino-5-methyl-3-pyridinyl)-2-(5-benzothiazolyl)-5-methyl-α-oxo-, (2R,5S)-

N-(6-amino-5-methylpyridin-3-yl)-2-[(2R,5S)-2-(1,3-benzothiazol -5-yl)-5-methylpiperidin-1-yl]-2-oxoacetamide

N-(6-amino-5-methylpyridin-3-yl)-2-[(2R,5S)-2-(1,3-benzothiazol -5-yl)-5-methylpiperidin-1-yl]-2-oxoacetamide
antineoplastic, TNG908, TNG 908, X7CRL5YNN5

Ralometostat (also known as TNG908) is an experimental, orally active oncology drug designed to treat advanced or metastatic solid tumors. It is classified as a potent, brain-penetrant, and selective methylthioadenosine (MTA)-cooperative PRMT5 inhibitor.

Developed by Tango Therapeutics, the drug targets specific genetic deletions frequently found in various human cancers.

Mechanism of Action

Ralometostat relies on a concept called synthetic lethality.

  • Target Deletion: It targets cancers that have a deletion of the methylthioadenosine phosphorylase (MTAP) gene. This deletion occurs in roughly 10% to 15% of all human cancers.
  • The "Trap": When the MTAP gene is missing, a metabolite called MTA builds up heavily inside the tumor cells.
  • Selective Killing: Ralometostat specifically binds to this PRMT5•MTA complex. This enables it to selectively kill MTAP-deleted cancer cells while sparing normal, healthy tissues.

This targeted approach bypasses the severe bone marrow toxicities caused by older, non-selective first-generation PRMT5 inhibitors.

Key Clinical Features

  • Blood-Brain Barrier Penetration: The drug is chemically optimized to cross the blood-brain barrier. This makes it highly effective in evaluating tumors within the central nervous system (CNS).
  • Therapeutic Targets: It is studied in clinical oncology settings for several tumor types, including:

Chemical & Trial Profile

Development Phase: Evaluated in Phase I/II clinical trials (such as NCT05275478) as a standalone precision therapy and in combination with other targeted inhibitors

Ralometostat is an orally available small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), with potential antiproliferative and antineoplastic activities. Upon oral administration, ralometostat selectively binds to PRMT5 and inhibits its function. By inhibiting its methyltransferase activity, levels of both monomethylated and dimethylated arginine residues in histones H2A, H3 and H4 are decreased. This modulates the expression of genes involved in several cellular processes, including cellular proliferation. This may increase the expression of antiproliferative genes and/or decrease the expression of genes that promote cell proliferation, which may lead to decreased growth of rapidly proliferating cells, including cancer cells. PRMT5, a type II methyltransferase that catalyzes the formation of both omega-N monomethylarginine (MMA) and symmetric dimethylarginine (sDMA) on histones and a variety of other protein substrates involved in signal transduction and cellular transcription, is overexpressed in several neoplasms and is essential for the viability of cancer and normal cells. Elevated levels are associated with decreased patient survival. Methylthioadenosine phosphorylase (MTAP) is deleted in certain cancer cells leading to an accumulation of methylthioadenosine (MTA). As MTA binds to and partially inhibits PRMT5, MTAP-null cancer cells are specifically sensitive to PRMT5 inhibitors. This may spare normal, healthy cells that are without MTAP-deletions and lower systemic toxicity.

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US358600101&_cid=P11-MSTR3S-83508-1

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US399951504&_cid=P11-MSTR3S-83508-1

Example 1. The synthesis of N-(6-amino-5-methylpyridin-3-yl)-2-((2R,5S)-2-(benzo[d]thiazol-5-yl)-5-methylpiperidin-1-yl)-2-oxoacetamide (Compound (I)) and N-(6-amino-5-methylpyridin-3-yl)-2-((2S,5R)-2-(benzo [d]thiazol-5-yl)-5-methylpiperidin-1-yl)-2-oxoacetamide (Compound (Ia))

The enantiomers were separated by chiral HPLC (column: IC II, Hexane-IPA-MeOH, 50-25-25, 12 ml/min as mobile phase) to give the two individual enantiomers Compound (Ia)N-(6-amino-5-methylpyridin-3-yl)-2-((2 S, 5R)-2-(benzo[d]thiazol-5-yl)-5-methylpiperidin-1-yl)-2-oxoacetamide (161 mg, 393.16 μmol, 97.28% yield) RetTime=32.4 min, [α]21D=−176.7°(c=0.1 g/100 mL, EtOH) and Compound (I)N-(6-amino-5-methylpyridin-3-yl)-2-((2R,5S)-2-(benzo[d]thiazol-5-yl)-5-methylpiperidin-1-yl)-2-oxoacetamide (160 mg, 390.72 μmol, 96.68% yield) RetTime=45.8 min, [α]21D=+191.5° (c=0.1 g/100 mL, EtOH).

Compound (I): RT (IC, Hexane-IPA-MeOH, 50-25-25, 0.6 ml/min)=47.098 min.

       1H NMR (600 MHz, DMSO-d6) δ 0.98-1.06 (m, 3H), 1.30-1.42 (m, 1H), 1.66-1.75 (m, 1H), 1.82-1.91 (m, 1H), 1.95-2.04 (m, 3H), 2.06-2.23 (m, 1H), 2.26-2.35 (m, 1H), 2.76-3.27 (m, 1H), 3.38-4.06 (m, 1H), 5.26-5.60 (m, 1H), 5.60-5.76 (m, 2H), 7.39-7.46 (m, 1H), 7.50 (s, 1H), 7.92-8.01 (m, 1H), 8.01-8.06 (m, 1H), 8.13-8.20 (m, 1H), 9.37-9.43 (m, 1H), 10.50-10.70 (m, 1H).
      LCMS(ESI): [M+H] + m/z: calcd 409.2; found 410.0; Rt=1.992 min.

Compound (Ia) RT (IC, Hexane-IPA-MeOH, 50-25-25, 0.6 ml/min)=35.176 min.

       1H NMR (600 MHz, DMSO-d6) δ 1.00-1.05 (m, 3H), 1.27-1.40 (m, 1H), 1.64-1.75 (m, 1H), 1.82-1.93 (m, 1H), 1.95-2.04 (m, 3H), 2.07-2.25 (m, 1H), 2.27-2.35 (m, 1H), 2.75-3.27 (m, 1H), 3.42-4.11 (m, 1H), 5.28-5.59 (m, 1H), 5.60-5.74 (m, 2H), 7.40-7.45 (m, 1H), 7.49 (s, 1H), 7.94-8.01 (m, 1H), 8.01-8.06 (m, 1H), 8.13-8.19 (m, 1H), 9.36-9.42 (m, 1H), 10.52-10.58 (m, 1H).
      LCMS(ESI): [M+H] + m/z: calcd 409.2; found 410.2; Rt=2.001 min.

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References

PAT

Piperidin-1-yl-N-pyridin-3-yl-2-oxoacetamide derivatives useful for the treatment of MTAP-deficient and/or MTA-accumulating cancersPublication Number:

KR-20230094196-APriority Date:

2020-07-31

//////////ralometostat, anax labs, antineoplastic, TNG908, TNG 908, X7CRL5YNN5

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Ratutrelvir

 

Ratutrelvir

CAS 2929236-94-0

MF C27H32F3N5O4 MW547.6 g/mol

(1R,2S,5S)-N-[(1S)-1-cyano-2-(2-oxo-1,3-dihydroindol-3-yl)ethyl]-3-[(2S)-3,3-dimethyl-2-[(2,2,2-trifluoroacetyl)amino]butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide

3-Azabicyclo[3.1.0]hexane-2-carboxamide, N-[(1S)-1-cyano-2-(2,3-dihydro-2-oxo-1H-indol-3-yl)ethyl]-3-[(2S)-3,3-dimethyl-1-oxo-2-[(2,2,2-trifluoroacetyl)amino]butyl]-6,6-dimethyl-, (1R,2S,5S)-

(1R,2S,5S)-N-{(1S)-1-cyano-2-[(3RS)-2-oxo-2,3-dihydro-1H-indol-3-yl]ethyl}-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
protease inhibitor, antiviral, TRX01, 83-0060, TRX 01, VR2S5588W2,

Ratutrelvir is an investigational new drug that is being evaluated by Traws Pharma[1] for the treatment of COVID-19 infections.[2][3] It is a 3C-like protease inhibitor.[3][4]

Clinical trials

Ratutrelvir is currently in a phase 2 clinical trial to test the effectiveness and safety of the drug in patients with COVID-19[5] and a preliminary analysis of the results has been released.[6]

Ratutrelvir (also known as TRX01 or 83-0060) is an investigational, oral antiviral medication being developed by Traws Pharma for the treatment of mild-to-moderate COVID-19.

Key Characteristics

  • Mechanism: It functions as a covalent inhibitor of the SARS-CoV-2 main protease (\(M^{pro}\) / 3CL protease), preventing the virus from replicating.
  • Ritonavir-Free: Unlike Paxlovid, ratutrelvir does not require a metabolic booster like ritonavir. This prevents severe drug-drug interactions and broadens its usability.
  • Dosing: It is designed as a once-daily oral regimen taken over 10 days.

Clinical Development & Trial Results

According to Phase 2 data released by Traws Pharma in early 2026:

  • Efficacy: Shows a comparable or faster time to sustained symptom resolution compared to Paxlovid.
  • No Viral Rebound: Patients treated with ratutrelvir experienced no viral rebound events.
  • Paxlovid-Ineligible Benefit: The drug successfully treated patients who could not take Paxlovid due to medical contraindications.
  • Fewer Side Effects: It reported fewer treatment-related adverse events (10% vs 23.3% for Paxlovid) and avoids taste disturbances (dysgeusia).

PAT

[WO2023093834A1]

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023093834&_cid=P11-MSWMDL-65476-1

Example 1: Preparation of (1R,2S,5S)-N-((2S)-1-amino-1-carbonyl-3-(2-carbonyldihydroindole-3-yl)propane-2-yl)-3-((S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butyryl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide (compound 1) 

[0138]The synthesis route is as follows:

The structural characterization data of compound 1-P2 are as follows: 

[0153]m/z(ESI):548[M+H] 。 

[0154]

1H NMR:(400MHz,DMSO-d6)δ10.58-10.41(m,1H),9.42-9.00(m,2H),7.39-7.26(m,1H),7.21-7.13(m,1H),7.03-6.78(m,2H),5.30-5.16(m,1H),4.44-4.30(m,1H),4.22(s,1H),4.00-3.86(m,1H),3.75-3.64(m,1H),3.58-3.47(m,1H),2.19-2.05(m,1H),1.63-1.54(m,1H),1.35(d,J＝7.7Hz,1H),1.04(s,3H),1.01-0.96(m,2H),0.94(s,2H),0.90-0.79(m,9H)。

PAT

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=4879FE25FD0F775B266E953E785747E1.wapp1nB?docId=WO2026122604&_cid=P11-MSWM6K-58737-1

Synthesis of compound (I)

31.

ASB

Synthesis of compound (I)

31.

ASB

PAT

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References

References

  1.  WO 2023245162, Rogovoy B, Kysil V, Berishvili V, Pauza CD, Zapata JC, Moreno SM, Li H, Orry A, Lam PC, Abagyan R, Savchuk N, "Compounds for treatment a coronavirus infection", published 2023-12-21, assigned to Trawsfynydd Therapeutics Inc.
  2.  "International Nonproprietary Names for Pharmaceutical Substances (INN) Recommended INN: List 94" (PDF). WHO Drug Information. 39 (3). World Health Organization: 809–1060 (976). 2025.
  3.  "Travatrelvir - Traws Pharma". AdisInsight. Springer Nature Switzerland AG. Retrieved 5 July 2026.
  4.  "Ratutrelvir | Ligand page". IUPHAR/BPS Guide to PHARMACOLOGY.
  5.  "Early-stage Trial to Determine a Safe and Effective Dose for Ratutrelvir in Patients With Mild to Moderate COVID-19". ClinicalTrials.gov. U.S. National Library of Medicine. 17 January 2026. Clinical trial record for NCT07157007. Retrieved 5 July 2026.
  6.  Contagion Editorial Team (8 July 2026). "Traws Pharma Reports Differentiated COVID-19 and Influenza Antiviral Progress". Contagion Live.
Clinical data
Other names83-0060, TRX01
Identifiers
IUPAC name
CAS Number2929236-94-0
PubChem CID169861725
IUPHAR/BPS13737
UNIIVR2S5588W2
Chemical and physical data
FormulaC27H32F3N5O4
Molar mass547.579 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

///////////ratutrelvir, anax labs, protease inhibitor, antiviral, TRX01, 83-0060, TRX 01, VR2S5588W2,

#ratutrelvir, #anax labs, #protease inhibitor, #antiviral, #TRX01, #83-0060, #TRX 01, #VR2S5588W2,

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