DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
.....FOR BLOG HOME CLICK HEREFlag and hits
ORGANIC SPECTROSCOPY
SUBSCRIBE
Subscribe in a reader
Enter your email address:
Delivered by FeedBurner
Subscribe to New Drug Approvals by Email
Recent Comments
 | shivkr2 on SPSR Excellence Award 2025 – S… |
 | Bonkasaurus on Infigratinib phosphate |
 | PALOVAROTENE | ORGAN… on Palovarotene |
| Pfizer just purchase… on Temanogrel | |
| Pfizer To Cash In On… on Temanogrel |
Setomagpran
Setomagpran
CAS 2991434-57-0
MF C22H19Cl2F6N5O MW 554.316
3-chloro-N-[(1R,3S)-3-{[6-chloro-2-(trifluoromethyl)quinolin-4-yl]amino}cyclohexyl]-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide
1H-Pyrazole-4-carboxamide, 3-chloro-N-[(1R,3S)-3-[[6-chloro-2-(trifluoromethyl)-4-quinolinyl]amino]cyclohexyl]-1-(2,2,2-trifluoroethyl)-
3-chloro-N-[(1R,3S)-3-{[6-chloro-2-(trifluoromethyl)quinolin-4-yl]amino}cyclohexyl]-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide
Mas-related G protein-coupled receptor antagonist, anti-inflammatory, MYX4KT647F
Setomagpran is a synthetic, small-molecule antagonist of the Mas-related G protein-coupled receptor X2 (MRGPRX2).
Because it blocks this specific receptor, it exhibits notable anti-inflammatory activity. The compound is primarily utilized as a reference standard and biochemical reagent in laboratory research settings
Setomagpran is the antagonist for mas-related G protein-coupled receptor (MRGPR), and exhibits anti-inflammatory activity.
Pat
Example 30
Synthesis of Example 30
Synthesis of 3-chloro-N-((1R,3S)-3-((6-chloro-2-(trifluoromethyl)quinolin-4-yl)amino) cyclohexyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide
Pat
WO 2022/067094 A1 (US20220098155)
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022067094&_cid=P10-MTZI7E-88068-1
PAT
WO 2023/192901 A1
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023192901&_cid=P10-MTZIR9-08517-1
EXAMPLE 30
Synthesis of 3-chloro-N-((1R,3S)-3-((6-chloro-2-(trifluoromethyl)quinolin-4-yl)amino) cyclohexyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide
To a stirring solution of ethyl 3-chloro-1H-pyrazole-4-carboxylate (200 mg, 1 Eq, 1.15 mmol) in DMF (5 mL) at room temperature was added cesium carbonate (1.12 g, 3 Eq, 3.44 mmol) portionwise over 2 minutes. After stirring for 30 minutes, 2,2,2- Trifluoroethyl trifluoromethanesulfonate (798 mg, 3 Eq, 3.44 mmol) was added dropwise over 2 minutes. The reaction mixture was stirred for 14 h. Water (5 mL) was added and the mixture wasextracted with EtOAc (3 x 5 mL), dried over sodium sulfate, filtered through Celite, and concentrated in vacuo to afford an 87:13 mixture of ethyl 3-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylate and ethyl 5-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylate that was used without further purification.
To a stirring solution of the crude ethyl 3-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylate and 5-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylate mixture (294 mg, 1 Eq, 1.15 mmol) in THF (6 mL) was added an aqueous solution of 1M sodium hydroxide (5.7 mL, 5 Eq, 5.73 mmol). The reaction mixture was heated at 50 °C for 14 h. 10 mL of 3 M HCl was added. The aqueous layer was extracted with EtOAc (3 x 10 mL), dried over sodium sulfate, filtered through Celite, and concentrated in vacuo to afford a mixture of 3-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylic acid and 5-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylic acid (276 mg, 1.21 mmol, 105 %) that was used without further purification.
To a stirring solution of (1S,3R)-N1-(6-chloro-2-(trifluoromethyl)quinolin-4-yl)cyclohexane-1,3-diamine hydrochloride (100 mg, 1 Eq, 0.264 mmol) in DMF (1.5 mL) were added a crude mixture of 3-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylic acid and 5-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxylic acid (60 mg, 1 Eq, 0.264 mmol), N-ethyl-N-isopropylpropan-2-amine (DIPEA) (0.138 mL, 3 Eq, 0.793 mmol) and HATU (111 mg, 1.1 Eq, 0.291 mmol). The reaction mixture was stirred at room temperature for 2 h. Purification by reversed phase HPLC (35 55% 0.1% formic acid in MeCN and 0.1% formic acid in H2O) afforded 3-chloro-N-((1R,3S)-3-((6-chloro-2-(trifluoromethyl)quinolin-4-yl)amino)cyclohexyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide (69 mg, 47% yield).
LCMS-ESI (m/z) calculated: 553.09 found 553.8 [M+H]+, RT = 10.114 min (Method 1)
1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 10.9 Hz, 1H), 8.35 (s, 1H), 8.06 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 9.0 Hz, 1H), 7.74 (dd, J = 9.0, 2.3 Hz, 1H), 7.48 (d, J = 7.9 Hz, 1H), 5.21 (q, J = 9.0 Hz, 1H), 4.01-3.83 (m, 2H), 2.17 (d, J = 12.0 Hz, 1H), 2.00-1.78 (m, 3H), 1.61-1.21 (m, 4H).
PAT
WO 2021/092240 A1
PAT
WO 2025/222040 A1
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
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
References
- Modulators of mas-related g-protein receptor x2 and related products and methodsPublication Number:US-2024124416-A1Priority Date:2022-03-30
- Modulators of mas-related g-protein receptor x2 and related products and methodsPublication Number:US-2024059667-A1Priority Date:2022-03-30
- Modulators of mas-related g-protein receptor x2 and related products and methodsPublication Number:US-2024124414-A1Priority Date:2022-03-30
- Quinoline derivatives as modulators of mas-related g-protein receptor x2 and related productsPublication Number:WO-2023192901-A1Priority Date:2022-03-30
- Modulators of mas-related g-protein receptor x2 and related products and methodsPublication Number:US-2024124415-A1Priority Date:2022-03-30
- Modulators of Mas-related G-protein receptor X2 and related products and methodsPublication Number:US-12129243-B2Priority Date:2022-03-30Grant Date:2024-10-29
- Quinoline derivatives as modulators of mas-related g-protein receptor x2 and related productsPublication Number:WO-2023192901-A9Priority Date:2022-03-30
- Modulators of Mas-related G-protein receptor X2 and related products and methodsPublication Number:US-12129244-B2Priority Date:2022-03-30Grant Date:2024-10-29
- Modulators of mas-related g-protein receptor x2 and related products and methodsPublication Number:US-2025026735-A1Priority Date:2022-03-30
- Quinoline derivatives as modulators of mas-related g-protein receptor x2 and related productsPublication Number:EP-4499632-A1Priority Date:2022-03-30
//////////setomagpran, anax labs, Mas-related G protein-coupled receptor antagonist, anti-inflammatory, MYX4KT647F
#setomagpran, #anax labs, #Mas-related G protein-coupled receptor antagonist, #anti-inflammatory, #MYX4KT647F
Seldegamadlin
Seldegamadlin
CAS 2713618-08-5
MFC48H52Cl2FN7O6 MW912.9 g/mol
- (3’R,4’S,5’R)-6”-chloro-4′-(3-chloro-2-fluorophenyl)-N-((1r,4R)-4-(4-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)piperidine-1-carbonyl)cyclohexyl)-2”-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3”-indoline]-5′-carboxamide
- (3’R,4’S,5’R)-6″-chloro-4′-(3-chloro-2-fluorophenyl)-N-((1r,4R)-4-(4-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)piperidine-1-carbonyl)cyclohexyl)-2”-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indoline]-5′-carboxamide
(3’R,4’S,5’R)-6”-chloro-4′-(3-chloro-2-fluorophenyl)-N-[trans-4-(4-{1-[(3RS)-2,6-dioxopiperidin-3-yl]-3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzimidazol-5-yl}piperidine-1-carbonyl)cyclohexyl]-2”-oxo-1”,2”-dihydrodispiro[cyclohexane-1,2′-pyrrolidine-3′,3”-indole]-5′-carboxamide
E3 ubiquitin-protein ligase Mdm2 (Hdm2) degrader, antineoplastic, KT 253, KT-253, VNP2BV6KGL
Seldegamadlin (also known as KT-253) is an advanced experimental oncology drug designed as a first-in-class, highly potent MDM2 PROTAC degrader and p53 stabilizer. It utilizes targeted protein degradation (TPD) technology to selectively eliminate the MDM2 oncoprotein, which restores the normal function of the critical tumor suppressor protein, p53.
How it Works
- Targeted Protein Degradation: It acts as a heterobifunctional PROTAC (proteolysis-targeting chimera). It features one end that binds tightly to MDM2 and another end that recruits the cereblon (CRBN) E3 ubiquitin ligase.
- p53 Stabilization: By tethering them together, it forces the cell’s natural disposal machinery to ubiquitinate and rapidly destroy MDM2. Because MDM2 normally suppresses and destroys p53, deleting MDM2 leads to an immediate up-regulation and stabilization of active p53.
- Apoptosis Activation: The sudden resurgence of active p53 fires up downstream targets like p21, forcing wild-type p53 cancer cells to halt their cell cycle (at the G2/M phase) and trigger rapid programmed cell death (apoptosis).
Primary Areas of Research
Seldegamadlin is actively being evaluated and researched for therapeutic efficacy against specific wild-type p53 malignancies:
- Hematologic Tumours: Including Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL).
- Solid Tumours: Such as Diffuse Large B-cell Lymphoma (DLBCL) and other forms retaining functional p53 signaling pathways
PAT
WO2023049790
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023049790&_cid=P11-MTWC17-46822-1
[001997] 3-[5-[1-(4-aminocyclohexanecarbonyl)-4-piperidyl]-3-methyl-2-oxo-benzimidazol-1-
yl]piperidine-2,6-dione (Intermediate WP)
[001998] Step 1 – Tert-butyl N-[4-[4-[1-(2,6-dioxo-3-piperidyl)-3-methyl-2-oxo-benzimidazol-5-yl]piperidine-1-carbonyl]cyclohexyl]carbamate. A mixture of 3-[3-methyl-2-oxo-5-(4-piperidyl)benzimidazol-1-yl]piperidine-2,6-dione (200 mg, 584 umol, Intermediate HE), (1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexane-1-carboxylic acid (142 mg, 584 umol, CAS# 53292-90-3), 1-methylimidazole (1.53 g, 18.6 mmol) , and TCFH (409 mg, 1.46 mmol) in ACN (1 mL) was stirred at 25 °C for 1 min. On completion, the reaction mixture was concentrated to give a residue. The crude product was purified by reversed-phase HPLC (0.1% FA condition) to give the title compound (120 mg, 36% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 7.11 (s, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 5.34 (dd, J = 5.6, 12.8 Hz, 1H), 4.62 – 4.54 (m, 1H), 4.10 – 3.98 (m, 1H), 3.49 ( s, 1H), 3.33 – 3.31 (m, 4H), 3.18 – 3.05 (m, 1H), 2.96 – 2.85 (m, 1H), 2.83 – 2.74 (m, 1H), 2.71 -2.62 (m, 3H), 2.05 – 1.94 (m, 1H), 1.86 – 1.67 (m, 6H), 1.61 – 1.40 (m, 7H), 1.39 (s, 9H).
[001999] Step 2 – 3-[5-[1-(4-aminocyclohexanecarbonyl)-4-piperidyl]-3-methyl-2-oxo-benzimidazol -1-yl]piperidine-2,6-dione. To a solution of tert-butyl N-[4-[4-[1-(2,6-dioxo-3-piperidyl)-3-methyl-2-oxo-benzimidazol-5-yl] piperidine-1-carbonyl]cyclohexyl]carbamate (60.0 mg, 105 umol) in DCM (1 mL) was added TFA (1.54 g, 13.5 mmol). The mixture was then stirred at 25 °C for 2 mins. On completion, the mixture was concentrated in vacuo to give the title compound (50.0 mg, 80% yield, TFA) as brown oil. LC-MS (ESI+) m/z 468.1 (M+H)+.
[00812] (3’R,4’S,5’R)-6”-chloro-4′-(3-chloro-2-fluorophenyl)-2”-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3”-indoline]-5′-carboxylic acid (Intermediate CI)
[00813] Step 1 – (3E)-6-chloro-3-[(3-chloro-2-fluoro-phenyl)methylene]indolin-2-one. A 500 mL 3-necked round bottom flask was charged with 6-chloroindolin-2-one (89.6 g, 535 mmol, CAS# 56341-37-8), 3-chloro-2-fluoro-benzaldehyde (84.8 g, 535 mmol, CAS# 85070-48-0), MeOH (1700 mL) and piperidine (9.11 g, 107 mmol). The mixture was stirred at 65 °C for 5 h, then at 25 °C for 12 h. On completion, the reaction mixture was filtered and the filter cake was dried under reduced pressure to give title product (160 g, 94% yield).1H NMR (400 MHz, DMSO-d6) δ = 10.87 (s, 1H), 7.82 – 7.63 (m, 2H), 7.56 (s, 1H), 7.39 (t, J = 8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.03 – 6.77 (m, 2H).
[00814] Step 2 – (E)-6-chloro-3-(3-chloro-2-fluorobenzylidene)indolin-2-one. (3E)-6-chloro-3-[(3-chloro-2-fluoro-phenyl)methylene]indolin-2-one (50 g, 162 mmol), (5R,6S)-5,6-diphenylmorpholin-2-one (49.3 g, 194 mmol, CAS# 282735-66-4), and cyclohexanone (31.8 g, 324 mmol, 33.6 mL) were dissolved in THF (75 mL) and toluene (750 mL) and 140 ºC for 12 hours. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate=8/1 to 5/1) to give the title compound (160 g 97% purity).1H NMR (400 MHz, DMSO-d6) δ = 10.79 (s, 1H), 7.95 ( t, J = 6.8 Hz, 1H), 7.45 – 7.37 (m, 1H), 7.33 – 7.20 (m, 4H), 7.18 – 7.09 (m, 4H), 7.07 – 6.98 (m, 2H), 6.86 – 6.75 (m, 3H), 6.66 (dd, J = 2.0, 8.4 Hz, 1H), 6.35 (d, J = 8.4 Hz, 1H), 5.44 (d, J = 11.2 Hz, 1H), 4.90 (d, J = 2.8 Hz, 1H), 4.58 (d, J = 11.2 Hz, 1H), 2.39 (d, J = 12.8 Hz, 1H), 2.24 – 2.09 (m, 1H), 1.42 – 1.18 (m, 4H), 1.10 – 0.78 (m, 1H).
[00815] Step 3 – (3’S,4’R,7’R,8’S,8a’R)-6”-chloro-8′-(3-chloro-2-fluorophenyl)-3′,4′-diphenyl-3′,4′,8′,8a’-tetrahydro-1’H-dispiro[cyclohexane-1,6′-pyrrolo[2,1-c][1,4]oxazine-7′,3”-indoline]-1′,2”-dione. H2SO4 (9.07 g, 92.5 mmol, 4.93 mL) was added to a solution of intermediate (E)-6-chloro-3-(3-chloro-2-fluorobenzylidene)indolin-2-one (9.0 g, 14.03 mmol) dissolved in MeOH (70 mL) and the resulting solution was heated to 50 °C for 5 hours. On completion, the reaction mixture was cooled to 0 °C and slowly neutralized with a solution of saturated sodium bicarbonate. The aqueous solution was extracted with ethyl acetate, and the organic layer was dried over sodium sulfate, filtered, concentrated to give the residue. The residue was purified by reverse phase flash [ACN/(0.1% FA in water), 0% to 90% ] to give title compound (7.0 g 84.2% purity).1H NMR (400 MHz, DMSO-d6) δ = 7.74 – 7.68 (m, 1H), 7.57 (s, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 7.2 Hz, 4H), 7.25 (d, J = 7.6 Hz, 6H), 7.19 – 7.11 (m, 6H), 7.10 – 6.98 (m, 4H), 6.94 – 6.88 (m, 1H), 6.65 – 6.58 (m, 1H), 5.39 – 5.27 (m, 1H), 4.89 – 4.75 (m, 1H), 4.42 -4.29 (m, 2H), 4.04 (q, J = 6.8 Hz, 1H), 3.63 – 3.53 (m, 2H), 3.40 (s, 3H), 2.22 – 2.12 (m, 1H), 2.05 – 1.94 (m, 3H), 1.40 – 1.32 (m, 2H), 1.28 – 1.13 (m, 3H).
[00816] Step 4 – Methyl (3’R,4’S,5’R)-6”-chloro-4′-(3-chloro-2-fluorophenyl)-1′-((1R,2S)-2-hydroxy-1,2-diphenylethyl)-2”-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3”-indoline]-5′-carboxylate. The resulting intermediate (3’S,4’R,7’R,8’S,8a’R)-6”-chloro-8′-(3-chloro-2-fluorophenyl)-3′,4′-diphenyl-3′,4′,8′,8a’-tetrahydro-1’H-dispiro[cyclohexane-1,6′-pyrrolo[2,1-c][1,4]oxazine-7′,3”-indoline]-1′,2”-dione (7.0 g, 10.3 mmol) was dissolved in ACN (78 mL), then CAN (11.3 g, 20.7 mmol) was added, followed by the addition of H2O (78 mL). The reaction was stirred at 25 °C for 30 min. On completion, the reaction mixture was quenched by adding the mixture to a cold saturated aqueous NaHCO3 solution (50 mL). The aqueous layer was extracted with ethyl acetate (20 mL x 3). The organic layer was separated, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the residue. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate=50/1 to 5/1) to give title compound (1.58 g, 31% purity). LC-MS (ESI+) m/z 477.2 (M+H)+.
[00817] Step 5 – (3’R,4’S,5’R)-6”-chloro-4′-(3-chloro-2-fluorophenyl)-2”-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3”-indoline]-5′-carboxylic acid. Methyl (3’R,4’S,5’R)-6”-chloro-4′-(3-chloro-2-fluorophenyl)-1′-((1R,2S)-2-hydroxy-1,2-diphenylethyl)-2”-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3”-indoline]-5′-carboxylate (2.00 g, 4.19 mmol) was dissolved in THF (14 mL) and LiOH.H2O (527 mg, 12.5 mmol) was added followed by water (14 mL) and MeOH (2 mL) and the reaction was stirred at 25 °C for 15 min. On completion, water (20 mL) was added and the reaction was slowly neutralized with 2M HCl and the suspension was stirred for 15 min. The resulting precipitate was filtered, washed with water to give title compound (1.50 g, 70% yield).1H NMR (400 MHz, DMSO-d6) δ = 10.75 – 10.57 (m, 1H), 10.55 (s, 1H), 7.61 – 7.54 (m, 1H), 7.50 – 7.44 (m, 1H), 7.41 – 7.34 (m, 1H), 7.18 – 7.12 (m, 1H),
7.08 – 7.02 (m, 1H), 6.72 – 6.66 (m, 1H), 4.72 – 4.65 (m, 1H), 4.54 – 4.47 (m, 1H), 3.18 – 3.15 (m, 1H), 2.22 – 2.13 (m, 1H), 1.83 – 1.70 (m, 2H), 1.64 – 1.52 (m, 3H), 1.51 – 1.43 (m, 2H), 1.42 – 1.34 (m, 1H), 1.04 – 0.92 (m, 1H), 0.89 – 0.77 (m, 1H). LC-MS (ESI+) m/z 463.2 (M+H)+.
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
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
References
- Mdm2 degraders and uses thereofPublication Number:WO-2023049790-A2Priority Date:2021-09-22
- Mdm2 degraders and uses thereofPublication Number:US-2024025878-A1Priority Date:2020-03-19
- Mdm2 degraders and uses thereofPublication Number:WO-2021188948-A1Priority Date:2020-03-19
- Methods of treating cancerPublication Number:WO-2023114933-A1Priority Date:2021-12-15
- Methods of treating cancerPublication Number:US-2023233546-A1Priority Date:2021-12-15
- Methods of treating cancerPublication Number:CN-118574613-APriority Date:2021-12-15
- Methods of treating cancerPublication Number:EP-4447959-A1Priority Date:2021-12-15
- Mdm2 degraders and uses thereofPublication Number:EP-4405359-A2Priority Date:2021-09-22
- Mdm2 degraders and uses thereofPublication Number:WO-2025096262-A1Priority Date:2023-11-01
- Mdm2 degraders and uses thereofPublication Number:WO-2024197219-A1Priority Date:2023-03-22
- Mdm2 degraders and uses thereofPublication Number:WO-2024197216-A2Priority Date:2023-03-22
- Mdm2 degraders and uses thereofPublication Number:US-2025352535-A1Priority Date:2022-06-06
- Mdm2 degraders and uses thereofPublication Number:WO-2023239697-A1Priority Date:2022-06-06
///////////////////seldegamadlin, anax labs, E3 ubiquitin-protein ligase Mdm2 (Hdm2) degrader, antineoplastic, KT 253, KT-253, VNP2BV6KGL
#seldegamadlin, #anax labs, #E3 ubiquitin-protein ligase Mdm2 (Hdm2) degrader, #antineoplastic, #KT 253, #KT-253, #VNP2BV6KGL
Secutrelvir
Secutrelvir
CAS 2996148-73-1
MF C23H16Cl2F3N5O2 MW522.3 g/mol
2-[5-(3-chloro-4-fluorophenyl)-3-(5-chloro-3-pyridinyl)-6-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)-2,4-dioxopyrimidin-1-yl]acetonitrile
2-(5-(3-chloro-4-fluorophenyl)-3-(5-chloropyridin-3-yl)-6-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetonitrile
[5-(3-chloro-4-fluorophenyl)-3-(5-chloropyridin-3-yl)-6-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]acetonitrile
protease inhibitor, antiviral, S-892216, S 892216, FMV68MJ8XK
Secutrelvir (also known by its developmental code S-892216) is an advanced, next-generation oral antiviral drug developed by the pharmaceutical company Shionogi. It functions as a potent SARS-CoV-2 3C-like protease (3CLpro / \(M^{\text{pro}}\)) inhibitor designed primarily for the treatment of COVID-19.
As of August 2026, the drug has entered late-stage development, with Shionogi moving into Phase 3 clinical trials to assess its efficacy and safety in patients.
Key Properties & Advantages
Unlike first-generation COVID-19 antivirals, secutrelvir was structurally optimized to address the limitations of existing treatments like Paxlovid (nirmatrelvir/ritonavir) and Shionogi’s own Xocova (ensitrelvir).
- No CYP Booster Required: Secutrelvir offers 100% oral bioavailability without needing a pharmacokinetic booster like ritonavir. This dramatically reduces the risk of severe drug-drug interactions that complicate Paxlovid prescriptions.
- Overcoming Viral Resistance: In laboratory assays, the compound demonstrates zero cross-resistance to viral mutants that have grown resistant to nirmatrelvir or ensitrelvir (such as those carrying E166V or M49L mutations).
- High Off-Target Selectivity: It features high selectivity (>15,000-fold) over human proteases, ensuring it specifically targets viral replication without disrupting normal human cellular functions.
- Broad Spectrum (Pan- β-CoV): The compound maintains high potency against a wide range of SARS-CoV-2 variants—including newer strains like Omicron JN.1—as well as other coronaviruses like SARS-CoV and MERS-CoV.
Mechanism of Action
Secutrelvir relies on a structure-based design incorporating a nitrile warhead. It enters the catalytic active site of the virus’s main protease (\(M^{\text{pro}}\)) and forms a reversible covalent bond with the catalytic amino acid residue cysteine C145. By binding to this pocket, it halts the protease from cutting viral polyproteins, effectively stopping viral replication in its tracks.
[Secutrelvir (Nitrile Warhead)] │ ▼ (Reversible Covalent Binding) [Cysteine C145 of 3CLpro] ──► Blocked Protease Activity ──► Viral Replication Stopped
Clinical Evaluation Status
- Pharmacokinetics: Clinical pharmacology data released by Shionogi Medical demonstrated excellent safety, high tolerability, and no clinically relevant food effects, meaning the drug can be taken with or without food.
- Phase 3 Trials (NCT07743580 / NCT07746544): Late-stage double-blind, placebo-controlled interventional studies are assessing the drug in symptomatic, non-hospitalized COVID-19 patients who are at risk of progressing to severe illness. To qualify for the trials, patients must receive the drug within 72 hours of symptom onset
- A Study of Secutrelvir in Participants With Coronavirus Disease 2019 (COVID-19) Who Are at High Risk for Progression to Severe DiseaseCTID:NCT07743580Phase:Phase 3Status:RecruitingDate:2026-08-25
- Study of Secutrelvir in Participants With COVID-19CTID:NCT07746544Phase:Phase 3Status:Not yet recruitingDate:2026-08-05
- A Study of S-892216 in Participants With COVID-19CTID:NCT06928051Phase:Phase 2Status:CompletedDate:2025-09-30
- A Drug-drug Interaction Study of S-892216 Coadministered With Carbamazepime to Healthy Adult ParticipantsCTID:NCT06751017Phase:Phase 1Status:CompletedDate:2025-03-11
Syn
https://patentscope.wipo.int/search/en/detail.jsf?docId=US451712998&_cid=P20-MTTHQ4-21870-1
Example 6
Synthesis of Compound (I-077)
Step 1 Synthesis of Compound (I-077)
| 1H-NMR (CDCl 3) δ: 2.75 (4H, t, J=12.0 Hz), 4.02 (4H, s), 4.74 (2H, s), 7.16-7.18 (2H, m), 7.32-7.35 (1H, m), 7.65 (1H, t, J=2.1 Hz), 8.43 (1H, d, J=2.3 Hz), 8.61 (1H, d, J=2.3 Hz). |
PAT
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
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
References
Uracil derivatives having virus replication inhibitory activity and pharmaceutical composition comprising the samePublication Number:
US-2025092056-A1Priority Date:2022-04-08
////secutrelvir, anax labs, protease inhibitor, antiviral, S-892216, S 892216, FMV68MJ8XK
#secutrelvir, #anax labs, #protease inhibitor, #antiviral, #S-892216, #S 892216, #FMV68MJ8XK
Rugocrixan
Rugocrixan
CAS911715-90-7
MF C19H25N5OS2, MF 403.6 g/mol
(2R)-2-[[2-amino-5-[(1S)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol
(R)-2-((2-Amino-5-(((S)-1-phenylethyl)thio)thiazolo[4,5-d]pyrimidin-7-yl)amino)-4-methylpentan-1-ol
(2R)-2-[(2-amino-5-{[(1S)-1-phenylethyl]sulfanyl}[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol
CX3C chemokine receptor 1 (CX3CR1) antagonist, antiinflammatory, KAND567, AZD8797, KAND 567, AZD 8797, S9Y83SS7PQ
Rugocrixan (also known by its developmental codes KAND567 and AZD8797) is a first-in-class, orally active small molecule drug candidate developed by Novakand Pharma (formerly Kancera). It acts as a potent, non-competitive allosteric antagonist of the CX3CR1 receptor, which is commonly referred to as the fractalkine receptor. By blocking this specific pathway, the drug prevents hyperinflammation and inhibits the proliferation and DNA repair mechanisms of certain cancer cells.
KAND567, a small molecule, blocks the fractaline (CX3CL1) receptor, which mediates the immune system response to inflammation. Because COVID-19 involves cytotoxic cells associated with this pathway, KAND567 is currently being tested as a treatment for those with the illness.
KAND567, a small molecule, blocks the fractaline (CX3CL1) receptor, which mediates the immune system response to inflammation. Because COVID-19 involves cytotoxic cells associated with this pathway, KAND567 is currently being tested as a treatment for those with the illness.
Key Clinical Developments and Therapeutic Focus
Originally acquired from AstraZeneca, the drug has advanced into multiple Phase II clinical trials. Novakand Pharma transitioned its core business strategy to focus heavily on orphan drug designations for niche, treatment-resistant conditions. Its primary areas of investigation include:
- Ovarian Cancer: Evaluated in the Phase IIa “KANDOVA” clinical trial for patients with treatment-resistant ovarian cancer. It functions by suppressing DNA repair in tumor cells, which enhances the effectiveness of platinum-based chemotherapy and drives the cancer cells into programmed cell death.
- Hematological Cancers: In preclinical studies alongside institutions like the Karolinska Institutet, rugocrixan has demonstrated a capability to block the unwanted growth-promoting effects of immune cells on advanced blood cancers, such as chronic lymphocytic leukemia (CLL).
- Cardioprotection: Investigated via the “FRACTAL” Phase IIa trial in patients suffering from acute myocardial infarction (STEMI) undergoing angioplasty. The drug met its safety endpoints and showed signals of protecting heart tissue by reducing myocardial bleeding and the risk of thrombosis.
Companion Prodrug
Novakand Pharma is also developing a second-generation, water-soluble phosphate prodrug named fosrugocrixan (KAND145). Once administered, fosrugocrixan is metabolized into the active form of rugocrixan, offering enhanced product properties for intravenous or alternative delivery methods.
Because rugocrixan targets a brand-new pharmacological pathway, the World Health Organization (WHO) assigned it a unique suffix stem, establishing it as the international nomenclature standard for this entire new class of CX3CR1 antagonists
- A Study to Evaluate the Safety of KAND567, in Combination With Carboplatin Therapy, in Women With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal CancerCTID:NCT06087289Phase:Phase 1/Phase 2Status:CompletedDate:2025-06-08
- Safety, Tolerability and Pharmacokinetics After Continuous Infusion of KAND567CTID:NCT06030375Phase:Phase 1Status:CompletedDate:2023-09-11
- KAND567 Versus Placebo in Subjects Hospitalized With COVID-19CTID:NCT06012565Phase:Phase 2Status:TerminatedDate:2023-08-25
- KANDOVA – A two-part Phase Ib/IIa study to evaluate the safety and tolerability of KAND567, in combination with carboplatin therapy, and to determine the Recommended Phase II Dose (RPIID) of KAND567. An open-label, multicenter dose escalation study with an expansion cohort in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.EudraCT:2022-002792-11Phase:Phase 2Status:Trial now transitionedDate:2023-03-27
- KAND567 Versus Placebo in Subjects Hospitalized with COVID-19. A Phase II, Randomized, 2-Arm Parallel-Group, Double-blind Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics.EudraCT:2020-002322-85Phase:Phase 2Status:Completed, Prematurely EndedDate:2020-07-02
SYN
PAT
WO 2006/107258.
PAT
EP1869056
https://patentscope.wipo.int/search/en/detail.jsf?docId=EP14857146&_cid=P20-MTP714-98881-1
Example 12
(2R)-2-[{2-Amino-5-[(1-phenylethyl)thio][1,3]thiazolo[4,5-d]pyrimidin-7-yl}(methyl)amino]-4-methylpentan-1-ol
a) (2R)-2-[[2-Amino-5-(benzylthio)[1,3]thiazolo[4,5-d]pyrimidin-7-yl](methyl)amino]-4-methylpentan-1-ol
[0097] 5-(Benzylthio)-7-chloro[1,3]thiazolo[4,5 -d]pyrimidin-2-amine (1.5 g, 4.86 mmol), DIPEA (691 mg, 5.35 mmol) and ( R)- N-methylleucinol (956 mg, 7.29 mmol) were mixed in NMP (7.5 mL). The resulting solution was stirred at 110 °C under a nitrogen atmosphere for 2 days. After cooling to room temperature the reaction mixture was poured onto ice. The resulting yellow precipitate was collected by filtration, washed with water and dried in vacuo. The crude product was purified by flash column chromatography on silica (DCM:EtOAc 50:50 to 0:100) to give 1.42 g (72% yield) of the title compound as a yellow solid.
1H NMR (DMSO-d 6) 7.97 (br s, 2H), 7.40 (m, 2H), 7.28 (m, 2H), 7.21 (m, 1H), 4.73 (dd, 1H), 4.64 (br s, 1H), 4.32 (br s, 2H), 3.52-3.37 (m, 2H), 3.00 (s, 3H), 1.55-1.35 (m, 2H), 1.27 (m, 1H), 0.88 (d, 3H), 0.80 (d, 3H);
MS (ESI +) m/ z 404 [M+H] +.
PAT
RU0002411245
PAT
WO2019219771
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019219771&_cid=P20-MTP714-98881-2
(2R)-2-[(2-amino-5-{[(1S)-1- phenylethyl]thio}[1 ,3]thiazolo[4,5-c/]pyrimidin-7-yl)amino]-4-methylpentan-1-ol is known to be a potent antagonist .
3.4 Preparation of (2R)-2-r(2-amino-5-(r(1 S)-1 -phenylethyllthio)ri ,3lthiazolor4,5-c/1Pyrimidin-7-yl)aminol-4-methylpentan-1 -ol.xHCI (5)
.xHCI
Compound 4 (1 .852 g, 5.74 mmol), DIPEA (1.1 12 g, 8.61 mmol) and D-leucinol (1.008 g, 8.61 mmmol) were dissolved in NMP (12 ml.) and the mixture was stirred at 120 °C in a sealed pyrex tube (start: 17:40).
HPLC after 15.5 h: ca. 98% conversion
HPLC after 19.5 h: >99% conversion
Work up: Ice water was poured into the mixture. Initially a solid was formed, but at the end of the addition the solid collapsed to a dark brown oil. EtOAc (50 ml.) was added and the phases were separated. The aqueous phase was extracted with EtOAc (2×25 ml_), and the combined organic phases were washed with water (8 ml_), sat. NaHC03 (3×8 ml_), water (8 ml.) and brine (8 ml_), dried over MgS04, filtered and evaporated. Dried in vacuum to yield 2.697 g of crude material as a brown oil. HPLC purity: ca. 92%. The oil was dissolved in MEK (ca. 18 mL) and cone. HCI (12.5 M, 574 pL, 7.18 mmol) was added. There was no spontaneous precipitation of the HCI salt. The mixture was gently stirred at RT and after ca. 20 min precipitation occurred. The mixture was stirred gently for 2.5 h and the solid was isolated by filtration on a P3 sintered glass filter. The solid was washed with three portions of MEK and was then dried in vacuum at 60 °C for 2.5 days. Yield (batch 1 ): 1 .224 g (48.5%) of the product as hydrochloride salt.
HPLC purity: 99.0% (basic method);
97.4% (acidic method).
A substantial amount of solids passed through the filter into the filtrate. The solids were isolated by centrifugation and the supernatant was removed by pipette. The solid was washed with two portions (ca. 2×5 mL) of MEK. After the last supernatant was removed the product was dried in vacuum at 60 °C for 2.5 days. Yield (batch 2): 324 mg (12.8%) of the product as hydrochloride salt.
HPLC purity: 99.0% (basic method);
97.5% (acidic method).
Combined yield: 1.548 g (61 .3%)
Both batches contain ca. 0.07% DMF (w/w). The DMF was already present in the starting material.
Further purification of the combined batches
The two batches of compound 5 were combined (1.338 g, 3.041 mmol) in a 50 mL roundbottomed flask and water (6 mL) was added followed by 2M NaOH (1.6 mL, 3.2 mmol). The mixture was stirred and EtOAc (40 mL) was added. An additional 0.5 mL (1 mmol) 2M NaOH was added during stirring. After 15 min all of the solids were dissolved and the phases were separated. The pH of the aqueous phase was measured with a pH stick =>pH=7. More 2M NaOH (0.4 mL, 0.8 mmol) was added to the aqueous phase resulting in a pH of 10. The aq. phase was extracted with EtOAc (25 mL) and the phases were separated. The combined organic phases were dried over Na2S04, filtered and evaporated to yield the free base as a crystalline beige solid. The free base was dissolved in MEK (15 mL) and HCI (37%, 12.5 M, 255 pL, 3.19 mmol) was added during stirring. A white precipitate was immediately formed. The mixture was stirred gently for 2 h and the solid was collected by filtration on a P4 sintered glass filter. The solids were washed with MEK (5 mL) and dried in vacuum at 60 °C for 3 h. Yield: 1.187 g (89% based on the unpurified material) of 99% pure product as a white solid. 1H NMR (600 MHz, CD30D) d ppm 7.49 (d, J=7.3 Hz, 2 H) 7.37 (t, J=7.6 Hz, 2 H) 7.27 – 7.32 (m, 1 H) 5.23 (q, J=7.0 Hz, 1 H) 4.60 – 4.70 (m, 1 H) 3.55 (d, J=5.5 Hz, 2 H) 1.83 (d, J=7.3 Hz, 3 H) 1.67 – 1.76 (m, 1 H) 1.58 -1.65 (m, 1 H) 1.48 – 1.54 (m, 1 H) 1.00 (d, J=6.7 Hz, 3 H) 0.98 (d,J=6.7 Hz, 3 H). MS (ESI+) m/z 404 [M+H]+
The diasteromeric ratio of the final product reflects the enantiomeric ratio of the starting material (compound 1 ), which was 99.7% (S).
1H NMR: The spectrum looks very pure. Trace amounts of DMF were, however, detected.
Comparative Example 4 – Process scale two-step procedure for the synthesis of 6-amino-2-{r(1S)-1-phenylethvnsulfanyl)pyrimidin-4-ol (1 )
Step 1 Step 2
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
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
References
- Novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivativesPublication Number:CA-2604017-CPriority Date:2005-04-06Grant Date:2012-03-06
- Novel 5-substituted 7-amino [1,3] thiazolo [4,5-D] pyrimidine derivativesPublication Number:JP-5165553-B2Priority Date:2005-04-06Grant Date:2013-03-21
- Novel 5,7-Disubstituted [1,3]Thiazolo[4,5-D]Pyrimidin-2(3H)-One Derivatives 794Publication Number:US-2009124637-A1Priority Date:2005-04-06
- New derivatives of 5, 7-disubstituted [1, 3] thiazolo[4, 5-d] pyrimidine-2(3h)-onePublication Number:RU-2411245-C9Priority Date:2005-04-06Grant Date:2011-05-27
- Novel 5-Substituted 7-Amino-[1,3]Thiazolo[4,5-D]Pyrimidine Derivatives 793Publication Number:US-2008214578-A1Priority Date:2005-04-06
- NEW DERIVATIVES OF 5-SUBSTITUTED 7-AMINO-[1, 3] THIAZOLO [4, 5-d]PYRIMIDINEPublication Number:RU-2419623-C2Priority Date:2005-04-06Grant Date:2011-05-27
- Novel 5,7-disubstituted [1,3] thiazolo [4,5-D] pyrimidin-2 (3H) -one derivativesPublication Number:JP-2008535834-APriority Date:2005-04-06
//////////rugocrixan, anax labs, CX3C chemokine receptor 1 (CX3CR1) antagonist, antiinflammatory, KAND567, AZD8797, KAND 567, AZD 8797, S9Y83SS7PQ
#rugocrixan, #anax labs, #CX3C chemokine receptor 1 (CX3CR1) antagonist, #antiinflammatory, #KAND567, #AZD8797, #KAND 567, #AZD 8797, #S9Y83SS7PQ
Romaciclib
Romaciclib
CAS 1609522-33-9
MWC15H18Br2N4 MF414.14 g/mol
6,7-dibromo-5-methyl-2-piperazin-1-yl-1,3-diazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene
7,8-dibromo-9-methyl-2-(piperazin-1-yl)-5,6-dihydro-4Himidazo[4,5,1-ij]quinoline
cyclin-dependent kinase inhibitor, antineoplastic, RVU-120, SEL-120, SEL120-34, SEL120-34A, RVU 120, SEL 120, ORPHAN DRUG, 6LGR0RYY5Q
Romaciclib is an investigational new drug being evaluated by Ryvu Therapeutics for the treatment of acute myeloid leukaemia (AML). It is a dual inhibitor of CDK8 and CDK19.[1][2][3]
Romaciclib is an investigational, orally bioavailable small-molecule dual inhibitor of cyclin-dependent kinases 8 and 19 (CDK8 and CDK19), being developed by Ryvu Therapeutics for the treatment of hematologic malignancies such as acute myeloid leukemia (AML) and myelofibrosis.
Mechanism of Action
- Targeted Inhibition: Romaciclib selectively targets CDK8 and CDK19 to disrupt oncogenic transcription programs essential for cancer cell survival while minimizing off-target effects.
- Oral Administration: As an oral pill, it offers convenience and supports long-term therapy compliance compared to intravenous treatments.
- Combination Potential: Preclinical and clinical evaluations show it helps overcome resistance mechanisms—such as restoring sensitivity to venetoclax (VEN) in relapsed/refractory AML—and exhibits synergistic activity with JAK inhibitors in myelofibrosis models.
Clinical Development
- Acute Myeloid Leukemia (AML): Evaluated in the Phase II RIVER-81 study in combination with venetoclax, showing encouraging anti-leukemic activity and durable responses in patients with relapsed or refractory disease.
- Myelofibrosis (MF): Investigated as a monotherapy or combined with ruxolitinib in the Phase II POTAMI-61 trial
- RVU120 Rollover StudyCTID:NCT06987058Phase:Phase 2Status:Enrolling by invitationDate:2026-07-28
- RVU120 in Patients With Intermediate or High-risk, Primary or Secondary MyelofibrosisCTID:NCT06397313Phase:Phase 2Status:RecruitingDate:2025-09-23
- RVU120 for Treatment of Anemia in Patients With Lower-risk Myelodysplastic NeoplasmsCTID:NCT06243458Phase:Phase 2Status:Active, not recruitingDate:2025-05-22
- Safety and Efficacy of RVU120 for Treatment of Relapsed/Refractory AMLCTID:NCT06268574Phase:Phase 2Status:Active, not recruitingDate:2025-05-08
- Safety and Efficacy of RVU120 Combined With Venetoclax for Treatment of Relapsed/Refractory AMLCTID:NCT06191263Phase:Phase 2Status:RecruitingDate:2025-04-13
- OriginatorSelvita
- DeveloperRyvu Therapeutics
- ClassAntineoplastics; Halogenated hydrocarbons; Imidazoles; Piperazines; Quinolones; Small molecules
- Mechanism of ActionCyclin dependent kinase 19 inhibitors; Cyclin-dependent kinase 8 inhibitors
- Orphan Drug StatusYes – Acute myeloid leukaemia
- Phase IIAcute myeloid leukaemia; Myelodysplastic syndromes; Myelofibrosis; Solid tumours
- Phase IMedulloblastoma
- 11 Jun 2026The US FDA reactivates the IND, enabling the initiation of the expansion cohort of phase II RIVER-81 trial in Acute myeloid leukaemia at the recommended dose of 150 mg once daily (QD)
- 11 Jun 2026Updated efficacy data from a phase II RIVER-81 trial in Acute myeloid leukaemia released by Ryvu Therapeutics
- 21 May 2026Ryvu Therapeutics plans a phase II ROVER-01 trial for Acute myeloid leukaemia, Myelodysplastic syndromes and Solid tumours in the Poland and Spain (NCT06987058)
Romaciclib is an orally bioavailable inhibitor of cyclin-dependent kinases 8 and 19 (CDK8/19), with potential antineoplastic and chemoprotective activities. Upon oral administration, romaciclib targets, binds to and inhibits the activity of CDK8/19, which prevents activation of CDK8/19-mediated oncogenic signaling pathways, blocks selective transcription of various tumor-promoting genes, and inhibits proliferation of CDK8/19-overexpressing tumor cells. CDK8/19, serine/threonine kinases involved in the regulation of the cell cycle, are overexpressed in certain cancer cell types and play key roles in tumor cell proliferation.
PAT
US20150274726
https://patentscope.wipo.int/search/en/detail.jsf?docId=US152387110&_cid=P10-MTMCT7-27170-1
7,8-dibromo-9-methyl-2-(piperazin-1-yl)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline,
PAT
- Substituted tricyclic benzimidazoles as kinase inhibitorsPublication Number:EP-2917217-B1Priority Date:2012-11-08Grant Date:2017-03-08
- Substituted tricyclic benzimidazoles as kinase inhibitorsPublication Number:CN-104903321-APriority Date:2012-11-08
- SUBSTITUTED TRICYCLIC BENZIMIDAZOLS, THEIR USES, AND PHARMACEUTICAL COMPOSITIONPublication Number:BR-112015010019-B1Priority Date:2012-11-08
- Substituted tricyclic benzimidazoles as kinase inhibitorsPublication Number:US-9745299-B2Priority Date:2012-11-08Grant Date:2017-08-29
- Substituted tricyclic benzimidazoles as kinase inhibitorsPublication Number:US-2015274726-A1Priority Date:2012-11-08
- C. novyi for the treatment of solid tumors in humansPublication Number:EP-3730146-B1Priority Date:2013-03-29Grant Date:2022-05-04
- Clostridium nodarii for the treatment of human solid tumorsPublication Number:CN-105451750-BPriority Date:2013-03-29Grant Date:2023-03-10
- C. novyi for the treatment of solid tumors in humansPublication Number:EP-4108248-A1Priority Date:2013-03-29
- C. novyi for the treatment of solid tumors in non-human animalsPublication Number:US-12433920-B2Priority Date:2013-03-29Grant Date:2025-10-07
- C. novyi for the treatment of solid tumors in humansPublication Number:EP-4108248-B1Priority Date:2013-03-29Grant Date:2025-09-17
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
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
References
- “Romaciclib – Ryvu Therapeutics”. AdisInsight. Springer Nature Switzerland AG.
- Rajendra A, Yee KW (April 2026). “Clinical development of a CDK8/19 kinase inhibitor for acute myeloid leukemia”. Expert Opinion on Investigational Drugs. 35 (4): 253–256. doi:10.1080/13543784.2026.2656430. PMID 41931045.
- Pakulska U, Obacz M, Woźnicki J, Wiklik K, Chakraborty S, Micek M, et al. (January 2026). “Romaciclib, a CDK8/CDK19 inhibitor, can overcome venetoclax resistance through a combinatorial strategy”. bioRxiv 10.64898/2025.12.16.693978.
- Cyclin-Dependent Kinase 8: A New Hope in Targeted Cancer Therapy?Publication Name:Journal of Medicinal ChemistryPublication Date:2017-12-21PMID:29266937DOI:10.1021/acs.jmedchem.7b00901
- SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of serine phosphorylation of STAT1 and STAT5 transactivation domainsPublication Name:OncotargetPublication Date:2017-04-04PMCID:PMC5464911PMID:28422713DOI:10.18632/oncotarget.16810
- Discovery of a Novel and Potent Cyclin-Dependent Kinase 8/19 (CDK8/19) Inhibitor for the Treatment of CancerPublication Name:Journal of Medicinal ChemistryPublication Date:2024-05-01PMID:38690856DOI:10.1021/acs.jmedchem.4c00248
- Discovery of a novel oral type Ⅰ CDK8 inhibitor against acute myeloid leukemiaPublication Name:European Journal of Medicinal ChemistryPublication Date:2023-05-05PMID:36889252DOI:10.1016/j.ejmech.2023.115214
- Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Inhibitors of CDK8 for the Treatment of CancerPublication Name:Journal of Medicinal ChemistryPublication Date:2023-04-07PMID:37029334DOI:10.1021/acs.jmedchem.2c01718
- From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer TherapyPublication Name:Journal of Medicinal ChemistryPublication Date:2022-04-29PMID:35485642DOI:10.1021/acs.jmedchem.1c02064
- A comprehensive insight on the recent development of Cyclic Dependent Kinase inhibitors as anticancer agentsPublication Name:European Journal of Medicinal ChemistryPublication Date:2020-10-01PMID:32707525DOI:10.1016/j.ejmech.2020.112571
//////////romaciclib, ANAX LABS, cyclin-dependent kinase inhibitor, antineoplastic, RVU-120, SEL-120, SEL120-34, SEL120-34A, RVU 120, SEL 120, ORPHAN DRUG, 6LGR0RYY5Q
#romaciclib, #ANAX LABS, #cyclin-dependent kinase inhibitor, #antineoplastic, #RVU-120, #SEL-120, #SEL120-34, #SEL120-34A, #RVU 120, #SEL 120, #ORPHAN DRUG, #6LGR0RYY5Q
Rocavorexant
Rocavorexant
CAS 2115665-09-1
MFC18H19F3N8O MW420.39
N,6-dimethyl-3-(2H-1,2,3-triazol-2-yl)-N-[(2S)-1-{[5-(trifluoromethyl)pyrazin-2-yl]amino}propan-2-yl]pyridine-2-
carboxamide
orexin-1 receptor antagonist, INDV-2000, C4X-3256, INDV 2000, C4X 3256,
Rocavorexant (developmental codes INDV-2000 and C4X-3256) is a potent, selective, oral orexin-1 receptor (OX₁R) antagonist originally developed to treat opioid use disorder and other substance-related disorders.
Clinical development of the drug has been suspended. In April 2026, Indivior announced that it would not advance the drug internally for opioid use disorder because the Phase 2 proof-of-concept trial failed to meet its primary endpoint of “no treatment failure”.
Key Drug Profile
- Mechanism of Action: Highly selective antagonist for the human orexin-1 receptor (pIC50 of 9.1) compared to the orexin-2 receptor (pIC50 of 6.0).
- Target Pathway: Aims at relapse-related neural circuitry, anxiety modulation, and stress-induced addictive behaviors.
- Chemical Formula: C₁₈H₁₉F₃N₈O.
- Current Status: Suspended internally by Indivior, which is actively seeking external business development and out-licensing opportunities due to positive secondary data regarding abstinence and safet
Rocavorexant (INNTooltip International Nonproprietary Name; developmental code names C4X-3256 and INDV-2000) is an orexin OX1 receptor antagonist which is under development for the treatment of opioid-related disorders and other substance-related disorders.[1][2][3][4] It is taken orally.[1] The drug is under development by C4X Discovery and/or Indivior.[1][2] As of May 2026, development for all indications has been suspended.[1] The drug has reached phase 2 clinical trials for opioid-related disorders and phase 1 trials for substance-related disorders.[1][2][4]
Rocavorexant is the antagonist for orexin-1 receptor with pIC50 of 9.1 for human OX1 (while pIC50 for human OX2 is 6.0).
1. Primary patent — most important reference
WO2017129829A1 — “Therapeutic compounds”
Inventor: Barrie P. Martin
Priority: 29 January 2016
Publication: 3 August 2017
WO2017129829A1 – Google Patents
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017129829&_cid=P12-MTJHA5-23107-1
This patent explicitly identifies Rocavorexant as:
N,6-dimethyl-3-(2H-1,2,3-triazol-2-yl)-N-[(2S)-1-{[5-(trifluoromethyl)pyrazin-2-yl]amino}propan-2-yl]pyridine-2-carboxamide, and provides its preparation as Example 1.
The patent is particularly useful because it contains large-scale examples, not merely milligram medicinal-chemistry experiments.
Preparation of A/,6-dimethyl-3-(2H-1 ,2,3-triazol-2-yl)-A/-r(2S)-1 -f r5-(trifluoro methyl)pyrazin-2-yllamino)propan-2-yllpyridine-2-carboxamide (Example 1 , Scheme 3)
To a stirred solution of Int 11 (0.58 g, 2.1 mmol) in THF (2 mL) was added DIPEA (1 .0 mL, 5.8 mmol) followed by 2-chloro-5-(trifluoromethyl)pyrazine (0.39 g, 2.1 mmol) and the mixture was heated at 70 °C for 4 hrs. The reaction mixture was allowed to cool to ambient temperature and allowed to stand over the weekend. The reaction mixture was heated at 70 °C for a further 4 hrs with stirring and allowed to cool to ambient temperature. The reaction mixture was evaporated in vacuo. The residue was purified by preparative HPLC (Column: Waters Xbridge C18 (10 μιτι, 30 x 100 mm). Conditions: Water + 0.2% ammonium hydroxide [Eluent A]; MeCN + 0.2% ammonium hydroxide [Eluent B]. Gradient: 10 to 95% B) and then lyophilised to give title compound as a white solid (0.32 g)
LCMS (Method C): Two peaks at 4.20 and 4.39 min, 421 [M+H]+
1 H NMR (500 MHz, d4-MeOH) δ 8.38 (d, 0.15 H), 8.34 (bs, 0.15 H), 8.24 (d, 0.85 H), 8.03 (bs, 0.85 H), 7.99 (s, 0.30 H), 7.97 (s, 1 .70 H), 7.85 (bs, 1 .00 H), 7.57 (d, 0.15 H),
7.41 (d, 0.85 H), 4.98 (m, 0.15 H), 4.06 (bm, 0.85 H), 3.50 (d, 0.15 H), 3.47 (d, 0.85 H),
3.42 (d, 0.85 H), 3.39 (d, 0.15 H), 3.05 (s, 2.55 H), 2.83 (s, 0.45 H), 2.65 (s, 0.45 H), 2.45 (bs, 2.55 H), 1 .38 (d, 0.45 H), 1 .07 (bs, 2.55 H). Preparation of A/,6-dimethyl-3-(2H-1 ,2,3-triazol-2-yl)-A/-r(2S)-1 -U5-(trifluoro methyl)pyrimidin-2-yllamino)propan-2-yllpyridine-2-carboxamide
US patent
US 11,130,746 B2 — Therapeutic compounds
This is especially relevant because its claims specifically cover processes for preparing the compounds, including:
Route A: reaction of the pyridine acid/lithium salt with an amide-coupling reagent and the chiral amine.
Route B: reaction of
N-[(2S)-1-aminopropan-2-yl]-N,6-dimethyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carboxamide
with an appropriate heteroaryl leaving-group compound in the presence of a base.
The patent specifically lists thionyl chloride among the coupling reagents and DIPEA as an appropriate base for the heteroaryl substitution route.
Other patent-family references
- US 10,696,654 B2
- US 11,130,746 B2
- US 11,753,398
- US 12,441,709 B2
The later US family documents retain the Rocavorexant compound/process disclosure. For example, US10696654B2 reproduces the Example 1 synthesis and the Int 14 preparation.
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
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
References
- “Rocavorexant”. AdisInsight. 12 May 2026. Retrieved 5 June 2026.
- “Delving into the Latest Updates on Rocavorexant with Synapse”. Synapse. 9 May 2026. Retrieved 5 June 2026.
- Raymond JS, Vareed RD, Peters J, James MH (October 2025). “Found in translation: orexin receptor antagonism for the treatment of opioid use disorder”. Translational Psychiatry. 15 (1) 432. doi:10.1038/s41398-025-03571-5. PMC 12552597. PMID 41136352.
- Lorente JS, Sokolov AV, Ferguson G, Schiöth HB, Hauser AS, Gloriam DE (June 2025). “GPCR drug discovery: new agents, targets and indications”. Nature Reviews. Drug Discovery. 24 (6): 458–479. doi:10.1038/s41573-025-01139-y. PMID 40033110.
 | |
| Clinical data | |
|---|---|
| Other names | C4X-3256; C4X3256; INDV-2000; INDV2000 |
| Routes of administration | Oral[1] |
| Drug class | Orexin OX1 receptor antagonist |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2115665-09-1 |
| PubChem CID | 130295635 |
| ChemSpider | 133325612 |
| UNII | 8RJN30TJM6 |
| KEGG | D13324 |
| Chemical and physical data | |
| Formula | C18H19F3N8O |
| Molar mass | 420.400 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
////rocavorexant, anax labs, orexin-1 receptor antagonist, INDV-2000, C4X-3256, INDV 2000, C4X 3256,
#rocavorexant, #anax labs, #orexin-1 receptor antagonist, #INDV-2000, #C4X-3256, #INDV 2000, #C4X 3256,
New Drug Approvals 
