All you want to know about drugs..by Dr Anthony Melvin Crasto, Worlddrugtracker, email me ........... amcrasto@gmail.com, call +91 9323115463 India
DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai), INDIA, worlddrugtracker, 29Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.8 Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contributionn, सुकून उतना ही देना प्रभू, जितने से जिंदगी चल जाये।औकात बस इतनी देना,कि औरों का भला हो जाये।...........P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
[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.
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
Compound (I-055) (25.0 mg, 0.059 mmol), 6,6-difluoro-2-azaspiro[3.3]heptane trifluoroacetic acid salt (17.4 mg, 0.070 mmol), N, N-diisopropylethylamine (20.5 μL, 0.117 mmol), and DMF (0.5 mL) were mixed, and the solution was stirred at 60° C. for 2 hours. Water (2 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and filtered. The filtrate was concentrated, and ethyl acetate (0.05 mL), hexane (0.125 mL), and diisopropyl ether (0.125 mL) were added. The obtained precipitate was collected by filtration and washed with diisopropyl ether. The obtained solid was dried under reduced pressure to obtain Compound (I-077) (22.0 mg, 0.042 mmol, yield 72%).
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
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] +.
(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 (2x25 ml_), and the combined organic phases were washed with water (8 ml_), sat. NaHC03 (3x8 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. 2x5 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 )
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
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.
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. PMID41931045.
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". bioRxiv10.64898/2025.12.16.693978.
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
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.
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]+
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.
