Navlimetostat

 

Navlimetostat

CAS 2630904-45-7

ALSO 2630904-44-6

MF C23H18ClFN6O2 MW464.9 g/mol

• Benzonitrile, 2-(4-(4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-(cyclopropyloxy)-3-fluoro-, (2S)-
• (M)-27
• 2-[4-[4-(aminomethyl)-1-oxo-2H-phthalazin-6-yl]-2-methylpyrazol-3-yl]-4-chloro-6-cyclopropyloxy-3-fluorobenzonitrile

(2M)-2-{4-[4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl] -1-methyl-1H-pyrazol-5-yl}-4-chloro-6-(cyclopropyloxy)-3-fluorobenzonitrile
antineoplastic, MRTX-1719, BMS-986504, MRTX 1719, BMS 986504

Navlimetostat (also known as MRTX-1719 or BMS-986504) is an investigational, first-in-class oral targeted cancer therapy being developed by Bristol-Myers Squibb. It works by selectively binding to the PRMT5-MTA complex, exploiting synthetic lethality to kill cancer cells with MTAP gene deletions while sparing healthy cells.

Navlimetostat is currently in Phase 1/2 clinical trials for advanced solid tumors, including MTAP-deficient non-small cell lung cancer (NSCLC), pancreatic cancer, and glioblastoma.

Key highlights and ongoing research:

• Mechanism: In MTAP-deleted cancer cells, a metabolite called MTA accumulates and binds to PRMT5. Navlimetostat targets and inhibits this specific PRMT5-MTA complex, leading to tumor cell death.
• Clinical Trials: It is currently being investigated as a monotherapy (e.g., in MTAP-deleted advanced solid tumors) and in combination with other agents like pumitamig

• OriginatorMirati Therapeutics
• DeveloperBristol-Myers Squibb; Mirati Therapeutics
• ClassAntineoplastics; Small molecules
• Mechanism of ActionPRMT5 protein inhibitors
• Phase II/IIIAdenocarcinoma; Non-small cell lung cancer
• Phase I/IIMesothelioma; Neurilemmoma; Pancreatic cancer; Solid tumours
• 22 May 2026University of Southampton in collaboration with Bristol-Myers Squibb plans a phase II SELECTmeso1 trial for Malignant mesothelioma (Second-line therapy or greater) in United Kingdom in May 2026 (PO, Tablet) (NCT07602946)
• 13 May 2026Northwestern University plans a phase Ib/II trial for Solid tumours (Metastatic disease, Second-line therapy or greater, Combination therapy) in USA(PO) in December 2027 (NCT07594626)
• 12 May 2026M.D. Anderson Cancer Center plans a phase I/II trial for Non-small cell lung cancer (Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater) in USA (PO), in November 2026 (NCT07579221)

PRMT5 Inhibitor BMS-986504 is an orally bioavailable methylthioadenosine (MTA)-selective inhibitor of the protein arginine methyltransferase 5 (PRMT5), with potential antineoplastic activity. Upon oral administration, PRMT5 inhibitor BMS-986504 targets, binds to and inhibits PRMT5 that is bound to MTA, a complex that is elevated in methylthioadenosine phosphorylase (MTAP)-deleted cancer cells, thereby specifically inhibiting the function of PRMT5 solely within MTAP-deleted cancer cells and not in normal, healthy cells. By inhibiting the methyltransferase activity of PRMT5, 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 cancer cells. BMS-986504 also causes dysregulated RNA splicing and decreased retinoblastoma protein (pRb). Together, this decreases proliferation and increases apoptosis specifically in MTAP-deleted 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 essential for the viability of cancer and normal cells. It is overexpressed in several neoplasms. Elevated levels are associated with decreased patient survival. MTAP is deleted in certain cancer cells leading to an accumulation of the metabolite MTA; MTA binds to and partially inhibits the activity of PRMT5.

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021050915&_cid=P12-MR76CL-04796-1

[0186] Step 6: To a solution of 6-bromo-4-(chloromethyl)-2H-phthalazin-1-one 13c (148 g, crude) in DMF (1.5 L) was added (1,3-dioxoisoindolin-2-yl)potassium (121 g, 653 mmol). The reaction mixture was stirred at 90 °C for 2 hours and then cooled to 25 °C. The formed precipitate was filtered and washed with DMF (200 mL x 2) and the filter cake triturated with water (1.00 L), filtered and dried to give Intermediate F, 2-[(7-bromo-4-oxo-3H-phthalazin-1-yl)methyl]isoindoline-1,3-dione (162 g, 413 mmol, 76% yield) as a white solid.¹H NMR (400 MHz, DMSO-d₆) d = 12.59 (s, 1H), 8.43 (d, J = 1.2 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 1.6, 8.4 Hz, 1H), 7.97 - 7.93 (m, 2H), 7.92 - 7.86 (m, 2H), 5.19 (s, 2H). LCMS [M+1]: 383.9.

[0327] Step 4: A mixture of 4-chloro-6-(cyclopropoxy)-3-fluoro-2-(2-methylpyrazol-3-yl)benzonitrile (180 mg, 0.617 mmol, 1.00 eq) and N-bromosuccinimide (220 mg, 1.23 mmol, 2.00 eq.) in acetonitrile (10 mL) was stirred at 40 °C for 2 hours under a nitrogen atmosphere. After such time the mixture was concentrated and the residue was purified by prep-TLC (SiO₂, petroleum ether: ethyl acetate 20%) to give 2-(4-bromo-2-methyl-pyrazol-3-yl)-4-chloro-6-(cyclopropoxy)-3-fluoro-benzonitrile (170 mg, 0.455 mmol, 74% yield) as a white solid. LCMS [M+1] ⁺ = 371.8; ¹H NMR (400 MHz, CDCl₃) d = 7.61 (s, 1H), 7.55 (d, J = 6.0 Hz, 1H), 3.93 - 3.85 (m, 1H), 3.80 (s, 4H), 0.97 - 0.94 (m, 4H).

EXAMPLE 16-7 and 16-8

[0590] Example 4-230, 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile (30 mg, 0.065 mmol) separated by SFC (DAICEL CHIRALPAK IC (250 mm × 30 mm x 10 mm); mobile phase:

[0.1% NH₃H₂O isopropanol]; B%: 40% isocratic, 4.1 min cycle; 120 min total ) to give example 16-7 (ee > 99%, 13 mg, 0.026 mmol, 25% yield) as a yellow solid and example 16-8 (8 mg, ee = 84% ). Example 16-8 was then then further separated by SFC (DAICEL CHIRALPAK IC (250 mm × 30 mm,10 mm); mobile phase: [0.1% NH₃H₂O EtOH]; B%: 60% isocratic, 3.1 min cycle; total 50 min) to give Example 16-8 (ee > 99%, 4 mg, 0.007 mmol, 7% yield) as a yellow gum. Spectra data for Example 16-7: LCMS [M+1] ⁺ = 465.1; ¹H NMR (400 MHz, DMSO-d₆) d = 12.59 - 12.44 (s, 1H), 8.29 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 6.0 Hz, 1H), 7.75 (s, 1H), 7.67 (br d, J = 7.6 Hz, 1H), 4.23 - 4.17 (m, 1H), 3.86 (br s, 2H), 3.78 (s, 3H), 0.94 - 0.88 (m, 2H), 0.84 - 0.79 (m, 2H). Spectra data for Example 16-8: LCMS [M+1] ⁺ = 465.1; ¹H NMR (400 MHz, DMSO-d₆) d = 12.49 - 12.37 (s, 1H), 8.26 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 6.0 Hz, 1H), 7.73 (d, J = 1.6 Hz, 1H), 7.72 - 7.68 (m, 1H), 4.19 (m, 1H), 3.80 (s, 2H), 3.77 (s, 3H), 0.93 - 0.87 (m, 2H), 0.83 - 0.78 (m, 2H).

PAT

• MTA-synergistic PRMT5 inhibitorsPublication Number: CN-114728912-APriority Date: 2019-09-12
• Mta-cooperative prmt5 inhibitorsPublication Number: WO-2021050915-A1Priority Date: 2019-09-12
• MTA-Cooperative PRMT5 InhibitorsPublication Number: US-2021078994-A1Priority Date: 2019-09-12
• MTA-Cooperative PRMT5 InhibitorsPublication Number: US-2021079003-A1Priority Date: 2019-09-12

ADVERTISEMENT

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

Phone : +91 897704 2010 /  +91 9177075735, Email : info@anaxlab.com

#MedicinalChemistry, #DrugDiscovery, #OrganicSynthesis, #ChemicalLibrary, #BuildingBlocks, #SARStudies, #ChemistryInnovation, #medchem, #Drugdevelopment, #Biotech, #Biotechnology, #AnaxLaboratories, #Pharma

AS ON FEB2026 4.574 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

• Twitter
• FACEBOOK

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

References

• Dynamic Kinetic Resolution of Axially Chiral MRTX1719Publication Name: SynfactsPublication Date: 2022-10-18DOI: 10.1055/s-0041-1738738
• Design and evaluation of achiral, non-atropisomeric 4-(aminomethyl)phthalazin-1(2H)-one derivatives as novel PRMT5/MTA inhibitorsPublication Name: Bioorganic & Medicinal ChemistryPublication Date: 2022-10-01PMID: 35926325DOI: 10.1016/j.bmc.2022.116947
• Synthesis of MRTX1719Publication Name: SynfactsPublication Date: 2022-03-18DOI: 10.1055/s-0041-1737934
• Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP -Deleted CancersPublication Name: Journal of Medicinal ChemistryPublication Date: 2022-01-18PMID: 35041419DOI: 10.1021/acs.jmedchem.1c01900
• Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5Publication Name: Science (New York, N.Y.)Publication Date: 2016-03-11PMID: 26912361DOI: 10.1126/science.aad5944
• Synthesis of MRTX1719DOI: 10.1055/s-0041-1737934Publication Date: 2022Publication Name: Synfacts
• Dynamic Kinetic Resolution of Axially Chiral MRTX1719DOI: 10.1055/s-0041-1738738Publication Date: 2022Publication Name: Synfacts

////////navlimetostat, anax labs, antineoplastic, MRTX-1719, BMS-986504, MRTX 1719, BMS 986504

#navlimetostat, # labs, #antineoplastic, #MRTX-1719, #BMS-986504, #MRTX 1719, #BMS 986504

Nedizantrep

 

Nedizantrep

CAS 2376824-99-4

MF C20H19ClN6O3 MW 426.9 g/mol

• 1-[[3-[(3R,5R)-5-(4-chlorophenyl)oxolan-3-yl]-1,2,4-oxadiazol-5-yl]methyl]-2,7-dimethylpurin-6-one
• 1-[[3-[(3R,5R)-5-(4-Chlorophenyl)tetrahydro-3-furanyl]-1,2,4-oxadiazol-5-yl]methyl]-1,7-dihydro-2,7-dimethyl-6H-purin-6-one
• 6H-Purin-6-one, 1-[[3-[(3R,5R)-5-(4-chlorophenyl)tetrahydro-3-furanyl]-1,2,4-oxadiazol-5-yl]methyl]-1,7-dihydro-2,7-dimethyl-

1-[[3-[(3R,5R)-5-(4-chlorophenyl)oxolan-3-yl]-1,2,4-oxadiazol-5-yl]methyl]-2,7-dimethylpurin-6-one

1-({3-[(3R,5R)-5-(4-chlorophenyl)oxolan-3-yl]-1,2,4-oxadiazol-5-yl}methyl)-2,7-dimethyl-1,7-dihydro-6Hpurin-6-one
transient receptor potential (TRP) ion channel antagonist, GDC-6599, GDC 6599, RG 6341, RG-6341, ENQ95FVE4X

Nedizantrep (also known by its developmental code GDC-6599) is a potent, selective, and orally active chemical compound developed as a transient receptor potential ankyrin 1 (TRPA1) cation channel antagonist. It was originally designed by Roche Holding AG/Genentech to manage respiratory conditions, particularly chronic cough associated with asthma and Chronic Obstructive Pulmonary Disease (COPD).

Key Characteristics & Mechanism

• Target Engagement: It acts as a TRPA1 inhibitor with high potency, exhibiting an IC50 value of 5.3 nM in humans. [1, 2]
• Therapeutic Purpose: It blocks TRPA1 cation channels, which are thermoTRP channels known to function as sensor transducers for temperature, pain, and environmental irritants. Inhibiting this pathway prevents the sensory nerve hypersensitivity that triggers chronic coughing fits.
• Research Status: As per data recorded by platforms like the IUPHAR/BPS Guide to PHARMACOLOGY, its chemical structure was publically disclosed in late 2023, and it has been evaluated through Phase 2 clinical trials
• A Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough
• CTID: NCT05660850
• Phase: Phase 2
• Status: Completed
• Date: 2025-12-16

PAT

US10710994,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US251637879&_cid=P12-MRBG82-53830-1

Example 8: 1-((3-((3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl)methyl)-2,7-dimethyl-1H-purin-6(7H)-one

The overall Example 8 reaction scheme is as follows:

Step 4: Preparation of 1-((3-((3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl)methyl)-2,7-dimethyl-1H-purin-6(7H)-one

5-(chloromethyl)-3-[(3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl]-1,2,4-oxadiazole (8.40 g, 28.1 mmol, prepared according to a similar procedure as example 1), 2,7-dimethyl-1H-purin-6(7H)-one (5.07 g, 30.9 mmol) and potassium carbonate (11.6 g, 84.2 mmol) were charged in a 200 mL RBF. DMF (56 mL) was added and the mixture was stirred in a 40° C. oil bath for 2 hours. Heat was removed and the reaction mixture was transferred to a separatory funnel containing EtOAc (100 mL) and water (500 mL). The mixture was extracted with EtOAc (3×100 mL). The combined organic layers were washed with a mixture of water (40 mL) and brine (40 mL), dried over anhydrous Na 2SO 4, filtered and concentrated under reduced pressure to give the crude product (77% purity by LCMS). The crude brown oil was dissolved in EtOAc (100 mL) and Heptane (60 mL) was added dropwise which led to the slow formation of a solid. The mixture was stirred at 0° C. for 30 min. and the solid was collected on a Büchner funnel, rinsed with heptane and air dried for 15 min. to give a first lot of 1-((3-((3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl)methyl)-2,7-dimethyl-1H-purin-6(7H)-one (8.0 g, 18.7 mmol, 67% yield, 92% purity by LCMS) as a yellow solid. The filtrate was concentrated and it was purified by reverse phase chromatography (C18, MeCN/10 mM NH 4HCO 2 in H 2O, pH 3.8, 0 to 60% gradient) to afford a second lot of 1-((3-((3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl)methyl)-2,7-dimethyl-1H-purin-6(7H)-one (950 mg, 2.23 mmol, 8% yield, >99% purity by LCMS) as a white solid.

The first lot of desired product (8.0 g, 92% purity by LCMS) was combined with a third lot obtained from a previous batch (1.3 g, 96% purity by LCMS). The material was dissolved in EtOAc (250 mL) and the solvent was displaced with iPrOH on the rotavap (3 cycles of iPrOH addition (50 mL)/evaporation of 50 mL of solvent). During the process, a solid crashed out and the solvent was reduced to ˜100 mL on the rotavap. The suspension was cooled to 0° C. and the solid was collected on a Büchner funnel, rinsed with cold iPrOH and air dried for 15 min. to give a fourth lot of 1-((3-((3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl)methyl)-2,7-dimethyl-1H-purin-6(7H)-one (8.50 g, 99% purity by LCMS) as a light beige solid. Still not satisfied with the color of the purified material, it was dissolved in EtOAc (500 mL) and the brown solution was treated with 8 g of activated charcoal. The mixture was allowed to stir for 15 min. The suspension was filtered on celite and the cake was rinsed with EtOAc. The colorless filtrate was evaporated under reduced pressure to give a fifth lot of 1-((3-((3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl)methyl)-2,7-dimethyl-1H-purin-6(7H)-one (7.50 g, 99% purity by LCMS) as a white solid. Finally, the second lot (950 mg, >99% purity by LCMS) and the fifth lot (7.50 g, 99% purity by LCMS) were combined in a 200 mL RBF and iPrOH (100 mL) was added. The suspension was stirred in a 100° C. oil bath until full dissolution and water was added (3 mL). The flask was removed from oil bath and the light yellow clear solution was allowed to cool down at room temperature. The suspension was cooled in an ice bath and the solid was collected on a Buchner funnel, rinsed with cold iPrOH (20 mL) and air dried for 24 hours to give the title compound 1-((3-((3R,5R)-5-(4-chlorophenyl)tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl)methyl)-2,7-dimethyl-1H-purin-6(7H)-one (7.3 g) as a white solid. LCMS: purity=99.4%, MH +=427.2/429.2. 1H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.46-7.33 (m, 4H), 5.63 (s, 2H), 5.00 (t, J=7.4 Hz, 1H), 4.35 (dd, J=8.4, 7.5 Hz, 1H), 3.93 (s, 3H), 3.95-3.88 (m, 1H), 3.79-3.70 (m, 1H), 2.60 (s, 3H), 2.63-2.53 (m, 1H), 2.13 (ddd, J=12.7, 8.9, 7.8 Hz, 1H).

PAT

[WO2019182925A1]

EG 8

ADVERTISEMENT

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

Phone : +91 897704 2010 /  +91 9177075735, Email : info@anaxlab.com

#MedicinalChemistry, #DrugDiscovery, #OrganicSynthesis, #ChemicalLibrary, #BuildingBlocks, #SARStudies, #ChemistryInnovation, #medchem, #Drugdevelopment, #Biotech, #Biotechnology, #AnaxLaboratories, #Pharma

AS ON FEB2026 4.574 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

• Twitter
• FACEBOOK

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

References

Oxadiazole compounds as transient receptor potential channel inhibitors

Publication Number: EP-3768260-B1

Priority Date: 2018-03-19

Grant Date: 2025-10-08

• Oxadiazole transient receptor potential channel inhibitorsPublication Number: TW-202003510-APriority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: US-10710994-B2Priority Date: 2018-03-19Grant Date: 2020-07-14
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: TW-I829676-BPriority Date: 2018-03-19Grant Date: 2024-01-21
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: US-2025122184-A1Priority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: EP-3768260-A1Priority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: US-2019284179-A1Priority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: KR-20230070333-APriority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: US-12202824-B2Priority Date: 2018-03-19Grant Date: 2025-01-21
• Oxadiazole transient receptor potential channel inhibitorPublication Number: KR-102533094-B1Priority Date: 2018-03-19Grant Date: 2023-05-16
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: TW-202438496-APriority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: US-2020308161-A1Priority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: US-2023121700-A1Priority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: WO-2019182925-A1Priority Date: 2018-03-19
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: US-11655245-B2Priority Date: 2018-03-19Grant Date: 2023-05-23
• Oxadiazole transient receptor potential channel inhibitorsPublication Number: CN-111867585-APriority Date: 2018-03-19

////////////nedizantrep, anax labs, transient receptor potential (TRP) ion channel antagonist, GDC-6599, GDC 6599, RG 6341, RG-6341, ENQ95FVE4X

#nedizantrep, #anax labs, #transient receptor potential (TRP) ion channel antagonist, #GDC-6599, #GDC 6599, #RG 6341, #RG-6341, #ENQ95FVE4X

Nelremagpran

 

Nelremagpran

CAS 2492595-24-9

MFC15H9ClF4O3 MW 348.67 g/mol

3-[[2-Chloro-4-(trifluoromethyl)phenoxy]methyl]-2-fluorobenzoic acid

3-{[2-chloro-4-(trifluoromethyl)phenoxy]methyl}-2-fluorobenzoic acid
Mas-related G protein-coupled receptor inverse agonist, anti-inflammatory, MRGPRX4 modulator-2, BL83FAK6DZ,

Nelremagpran is an experimental drug that acts as a potent and selective antagonist (or possibly inverse agonist) of the MAS-related Gq protein-coupled receptor X4 (MRGPRX4). It has antiinflammatory effects in animal studies. This receptor is poorly characterised but is thought to be involved in immune system function, and development of selective ligands is essential for researching its role in the body.^[1][2]

Nelremagpran is an experimental drug that acts as a potent and selective antagonist or inverse agonist of the Mas-related G-protein-coupled receptor X4 (MRGPRX4). It was initially developed by Escient Pharmaceuticals, Inc. for its anti-inflammatory and anti-itch properties.

🧪 Core Mechanism

The drug targets MRGPRX4, a poorly characterized receptor found in the immune and nervous systems. It functions with high potency, exhibiting an half-maximal inhibitory concentration (IC50) of less than 100 nM.

🔬 Potential Research Applications

Because the receptor plays a significant role in mediating severe itch and pain pathways, Nelremagpran is actively used as a chemical probe to study:

• Chronic Pruritus: Conditions involving persistent, debilitating itch sensations, such as cholestatic pruritus.
• Autoimmune Diseases: Underlying mechanisms in conditions like psoriasis, multiple sclerosis, and Stevens-Johnson Syndrome.
• Inflammatory Sensation: How the body signals pain and immune hypersensitivity

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020198537&_cid=P12-MREAZN-03524-1

Synthesis of Compound 1-55

Step 4-4. Synthesis of methyl 3-(bromomethyl)-2-fluorc>benzoate (INT 4-C)

ADVERTISEMENT

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

Phone : +91 897704 2010 /  +91 9177075735, Email : info@anaxlab.com

#MedicinalChemistry, #DrugDiscovery, #OrganicSynthesis, #ChemicalLibrary, #BuildingBlocks, #SARStudies, #ChemistryInnovation, #medchem, #Drugdevelopment, #Biotech, #Biotechnology, #AnaxLaboratories, #Pharma

AS ON FEB2026 4.574 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

• Twitter
• FACEBOOK

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

References

Identifiers
IUPAC name
CAS Number	2492595-24-9
PubChem CID	155145968
ChemSpider	115008493
UNII	BL83FAK6DZ
ChEMBL	ChEMBL4855031
Chemical and physical data
Formula	C15H9ClF4O3
Molar mass	348.68 g·mol−1
3D model (JSmol)	Interactive image
SMILES
InChI

References

1.  WO 2020/198537, Yeager A, Selfridge B, Sainz M, Martinborough E, Boehm M, Huang, "Modulators of mas-related G-protein receptor x4 and related products and methods.", published 1 October 2020, assigned to Escient Pharmaceuticals, Inc.
2.  "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 38 (4). 2024.

• Modulators of Mas-related G-protein receptor X4 and related products and methodsPublication Number: US-11840521-B2Priority Date: 2019-03-28Grant Date: 2023-12-12
• Modulators of mas-related g-protein receptor x4 and related products and methodsPublication Number: EP-3946304-A1Priority Date: 2019-03-28
• Modulators of mas-related g-protein receptor x4 and related products and methodsPublication Number: US-2023159474-A1Priority Date: 2019-03-28
• Modulators of mas-related g-protein receptor x4 and related products and methodsPublication Number: US-2023053860-A1Priority Date: 2019-03-28
• Modulators of mas-related g-protein receptor x4 and related products and methodsPublication Number: US-2021032213-A1Priority Date: 2019-03-28
• Modulators of mas-related G-protein receptor X4 and related products and methodsPublication Number: US-11643399-B2Priority Date: 2019-03-28Grant Date: 2023-05-09
• Modulators of mas-related g-protein receptor x4 and related products and methodsPublication Number: US-2024300907-A1Priority Date: 2019-03-28
• Modulators of mas-related g-protein receptor x4 and related products and methodsPublication Number: WO-2020198537-A1Priority Date: 2019-03-28
• Modulators of MAS-related G protein receptor X4 and related products and methodsPublication Number: CN-113939288-BPriority Date: 2019-03-28Grant Date: 2025-04-25

//////////nelremagpran, anax labs, Mas-related G protein-coupled receptor inverse agonist, anti-inflammatory, MRGPRX4 modulator-2, BL83FAK6DZ,

#nelremagpran, #anax labs, #Mas-related G protein-coupled receptor inverse agonist, #anti-inflammatory, #MRGPRX4 modulator-2, #BL83FAK6DZ,

NETANASVIR

 

Netanasvir

CAS 2007900-70-9

MF C51H58N8O7 MW895.1 g/mol

methyl N-[(1R)-2-[(2S,4S)-2-[5-[7-[2-[(2S,5S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-5-methylpyrrolidin-2-yl]-3H-benzo[e]benzimidazol-7-yl]-2,3-dihydro-1H-inden-4-yl]-1H-imidazol-2-yl]-4-(methoxymethyl)pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamate

• Carbamic acid, N-[(1R)-2-[(2S,4S)-2-[5-[2,3-dihydro-7-[2-[(2S,5S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methyl-1-oxobutyl]-5-methyl-2-pyrrolidinyl]-1H-naphth[1,2-d]imidazol-7-yl]-1H-inden-4-yl]-1H-imidazol-2-yl]-4-(methoxymethyl)-1-pyrrolidinyl]-2-oxo-1-phenylethyl]-, methyl ester
• Methyl ((S)-1-((2S,5S)-2-(7-(7-(2-((2S,4S)-1-((R)-2-((methoxycarbonyl)amino)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-2,3-dihydro-1H-inden-4-yl)-1H-naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate
• methyl {(2S)-1-[(12S,15S,52S,54S,7R)-7-[(methoxycarbonyl)amino]-54-(methoxymethyl)-15-methyl-6-oxo-32,33-dihydro-21H,31H,41H-2(2,7)-naphtho[1,2-d]imidazola-4(4,2)-imidazola-1(2),5(2,1)-dipyrrolidina-3(4,7)-indena-8(1)-benzenaoctaphan-11-yl]-3-methyl-1-oxobutan-2-yl}carbamate
• Methyl N-[(1R)-2-[(2S,4S)-2-[5-[2,3-dihydro-7-[2-[(2S,5S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methyl-1-oxobutyl]-5-methyl-2-pyrrolidinyl]-1H-naphth[1,2-d]imidazol-7-yl]-1H-inden-4-yl]-1H-imidazol-2-yl]-4-(methoxymethyl)-1-pyrrolidinyl]-2-oxo-1-phenylethyl]carbamate

antiviral, Dongweizhuo, HCV, Antaitavir Hasophate, HEC 74647 PA, 4Y7YD32BYY

Netanasvir (commonly prescribed as netanasvir phosphate) is a direct-acting antiviral medication primarily used to treat chronic hepatitis C virus (HCV) infection. It was approved by the China National Medical Products Administration (NMPA) under the trade name Dongweizhuo.

Key Clinical Information

• Mechanism of Action: It acts as a potent and selective NS5A inhibitor. By targeting the HCV NS5A protein, it successfully blocks viral RNA replication, virion assembly, and viral clearance mechanisms.
• Combination Therapy: It is exclusively indicated for use in combination with encofosbuvir (an NS5B polymerase inhibitor).
• Target Genotypes: The combination regimen effectively treats adult patients with chronic HCV genotypes 1, 2, 3, or 6.
• Patient Profiles: It is suitable for patients who are either treatment-naïve or have been previously treated with interferon, with or without compensated liver cirrhosis.
• Administration & Elimination: Taken orally, the drug demonstrates high metabolic stability, with feces serving as its primary elimination pathway

• OriginatorSunshine Lake Pharma
• ClassAntivirals
• Mechanism of ActionHepatitis C virus NS 5 protein inhibitors
• RegisteredHepatitis C
• 08 Feb 2025Registered for Hepatitis C (Combination therapy, Treatment-experienced) in China (PO)
• 08 Feb 2025Registered for Hepatitis C (Combination therapy, Treatment-naive) in China (PO)
• 31 Dec 2023NMPA, China accepts NDA for netanasvir for Hepatitis C for review

Netanasvir is an antiviral drug used to treat hepatitis C virus (HCV).^[1] In China, netansavir is approved for use in combination with encofosbuvir for the treatment of adult patients with chronic HCV genotypes 1, 2, 3, or 6, who are either treatment-naive or have been previously treated with interferon.^[2]

PAT

Compounds as hepatitis c virus inhibitors and pharmaceutical uses thereof

Publication Number: WO-2016141890-A1

Priority Date: 2015-03-12

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2016141890&_cid=P22-MRH62L-18160-1

ADVERTISEMENT

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

Phone : +91 897704 2010 /  +91 9177075735, Email : info@anaxlab.com

#MedicinalChemistry, #DrugDiscovery, #OrganicSynthesis, #ChemicalLibrary, #BuildingBlocks, #SARStudies, #ChemistryInnovation, #medchem, #Drugdevelopment, #Biotech, #Biotechnology, #AnaxLaboratories, #Pharma

AS ON FEB2026 4.574 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

• Twitter
• FACEBOOK

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

References

1.  "Netanasvir phosphate - Sunshine Lake Pharma". Adis Insight. Springer Nature Switzerland AG.
2.  "Netanasvir Phosphate Capsules Approved for Marketing by China NMPA". National Medical Products Administration. 2025-06-11.

Clinical data
Trade names	东卫卓; Dongweizhuo
Legal status
Legal status	Rx in China
Identifiers
IUPAC name
CAS Number	2007900-70-9
PubChem CID	122535557
UNII	4Y7YD32BYY
Chemical and physical data
Formula	C51H58N8O7
Molar mass	895.074 g·mol−1
3D model (JSmol)	Interactive image
SMILES
InChI

//////////netanasvir, anax labs,  APPROVALS 2025, CHINA 2025, antiviral, Dongweizhuo, HCV, Antaitavir Hasophate, HEC 74647 PA, 4Y7YD32BYY

#netanasvir, #anax labs,  #APPROVALS 2025, #CHINA 2025, #antiviral, #Dongweizhuo, #HCV, #Antaitavir Hasophate, #HEC 74647 PA, #4Y7YD32BYY