Home » Posts tagged 'Antineoplastic' (Page 7)
Tag Archives: Antineoplastic
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 |
Muvadenant
Muvadenant
CAS 2459881-03-7
MF C21H26N4O4S , 430.5 g/mol
(5S)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy[1,3]thiazolo[4,5-c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5] decane-2-carboxamide
(5S)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1,3]thiazolo[4,5-c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide
adenosine receptor antagonist, antineoplastic, 6LSF69F6A8, M1069 , M 1069
Muvadenant is a small molecule drug. The usage of the INN stem ‘-adenant’ in the name indicates that Muvadenant is a adenosin receptor antagonist. Muvadenant has a monoisotopic molecular weight of 430.17 Da.
Adenosine is an ubiguitous modulator of numerous physiological activities, particularly within the cardiovascular, nervous and immune systems. Adenosine is related both structurally and metabolically to the bioactive nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and cyclic adenosine monophosphate (cAMP), to the biochemical methylating agent S-adenosyl-L-methione (SAM) and structurally to the coenzymes NAD, FAD and coenzym A and to RNA.
Via cell surface receptors, adenosine modulates diverse physiological functions including induction of sedation, vasodilatation, suppression of cardiac rate and contractility, inhibition of platelet aggregability, stimulation of gluconeogenesis and inhibition of lipolysis. Studies show that adenosine is able to activate adenylate cyclases, open potassium channels, reduce flux through calcium channels, and inhibit or stimulate phosphoinositide turnover through receptor-mediated
mechanisms (Muller C. E. and Stein B., Current Pharmaceutical Design, 2: 501 , 1996; Muller C. E., Exp. Opin. Ther. Patents, 7(5): 419, 1997).
Adenosine receptors belong to the superfamily of G-protein-coupled receptors (GPCRs). Four major subtypes of adenosine receptors have been
pharmacologically, structurally and functionally characterized (Fredholm et al., Pharm. Rev., 46: 143-156, 1994) and referred to as A1, A2A, A2B and A3. Though the same adenosine receptor can couple to different G-proteins, adenosine A1 and A3 receptors usually couple to inhibitory G-proteins referred to as G, and Go which inhibit adenylate cyclase and down-regulate cellular cAMP levels. In contrast, the adenosine A2A and A2B receptors couple to stimulatory G-proteins referred to as Gs that activate adenylate cyclase and increase intracellular levels of cAMP (Linden J., Annu. Rev. Pharmacol. Toxicol., 41 : 775-87 2001).
PAT
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: US-2022119412-A1Priority Date: 2019-01-22
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: EP-3914600-B1Priority Date: 2019-01-22Grant Date: 2024-08-07
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: CN-113939520-BPriority Date: 2019-01-22Grant Date: 2024-11-22
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: ES-2992081-T3Priority Date: 2019-01-22Grant Date: 2024-12-09
- Thiazolopyridine derivatives as adenosine receptor antagonists.Publication Number: JP-7600119-B2Priority Date: 2019-01-22Grant Date: 2024-12-16
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: AU-2020211697-A1Priority Date: 2019-01-22
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: KR-20210116572-APriority Date: 2019-01-22
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: CN-113939520-APriority Date: 2019-01-22
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: EP-3914600-A1Priority Date: 2019-01-22
- Thiazolopyridine derivative as an adenosine receptor antagonistPublication Number: JP-2022524914-APriority Date: 2019-01-22
- Combination therapy for cancerPublication Number: CN-117858723-APriority Date: 2021-06-07
- Combination treatment of cancerPublication Number: EP-4351640-A1Priority Date: 2021-06-07
- Combination Treatment of CancerPublication Number: JP-2024520764-APriority Date: 2021-06-07
- Combination Treatment of CancerPublication Number: US-2024279338-A1Priority Date: 2021-06-07
- Thiazolopyridine derivatives as adenosine receptor antagonistsPublication Number: WO-2020152132-A1Priority Date: 2019-01-22
- Novel crystalline forms of (s)-7-oxa-2-aza-spiro[4.5]decane-2-carboxylic acid [7-(3,6-dihydro-2h-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide and co-crystal forms thereofPublication Number: TW-202415667-APriority Date: 2022-08-02
- Novel crystalline forms of (s)-7-oxa-2-aza-spiro[4.5]decane-2-carboxylic acid [7-(3,6-dihydro-2h-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide and co-crystal forms thereofPublication Number: WO-2024028273-A1Priority Date: 2022-08-02
- Combination treatment of cancerPublication Number: WO-2022258622-A1Priority Date: 2021-06-07
- Combination treatment of cancerPublication Number: AU-2022288571-A1Priority Date: 2021-06-07
- Combination treatment of cancerPublication Number: CA-3220380-A1Priority Date: 2021-06-07
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020152132&_cid=P10-MHPOEV-06540-1
1. (5R)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin- 2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide 24
and (5S)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5- c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide 25
a. 4-chloro-5-iodo-3-nitropyridin-2-ol
Into a 250-mL round-bottom flask was placed 4-chloro-3-nitropyridin-2-ol (10.0 g, 54.4 mmol, 95%), N-lod-succinimid (NIS, 14.2 g, 59.9 mmol, 95%) in acetonitrile (115 mL). The solution was stirred for 1 h overnight at 80°C in an oil bath. The mixture was concentrated and the precipitate formed collected by filtration. The residue was washed with twice with petrol ether (500 mL) dried under vacuum at 60°C overnight. This resulted in 4-chloro-5-iodo-3-nitropyridin-2-ol (16.5 g, 97.9%, 97% purity) as a yellow solid. MS: m/z = 300.9 [M+H]+.
b. 4-chloro-5-iodo-2-methoxy-3-nitropyridine
Into a 500-mL round-bottom flask was placed 4-chloro-5-iodo-3-nitropyridin-2-ol (16.5 g, 53.3 mmol, 97%), Ag2CO3 (15.5 g, 53.3 mmol, 95%) in toluene (310 mL). To this suspension CH3I (15.9 g, 107 mmol, 95%) was added at 50°C and the mixture was stirred at 80°C for 4 h. The precipitate was collected by filtration and discarded. The filtrate was evaporated to dryness under vacuum and the residue purified by silica gel chromatography with ethyl acetate/petroleum ether (15:85).
This resulted in 4-chloro-5-iodo-2-methoxy-3-nitropyridine (9.90 g, 52.6%, 89% purity) as a light yellow solid. MS: m/z = 315.5 [M+H]+.
c. 4-chloro-5-iodo-2-methoxypyridin-3-amine
Into a 250-mL 3-necked round-bottom flask was placed 4-chloro-5-iodo-2-methoxy-3-nitropyridine (9.90 g, 28.0 mmol, 89%), iron (16.5 g, 281 mmol, 95%) and NH 4C (9.40 g, 174 mmol, 99%) in ethanol (152 mL) and water (30 mL). The mixture was stirred for 2 h at 80°C in an oil bath. The reaction mixture was filtered over Celite, washed with ethanol and the mother liquor was concentrated to dryness. The residue was stirred for 30 min. with 100 ml water at 60°dried in vacuo. This resulted in 4-chloro-5-iodo-2-methoxypyridin-3-amine (7.20 g, 75%, 83% purity) as an off-white solid. It was used without further purification in the next step. MS: m/z = 285.9 [M+H]+.
d. N-[7-iodo-4-methoxy-[1,3]thiazolo[4,5-c]pyridin-2-yl]benzamide
Into a 500-mL round-bottom flask was placed 4-chloro-5-iodo-2-methoxypyridin-3-amine (7.20 g, 21.0 mmol, 83%) in acetone (150 mL) and benzoyl isothiocyanate (5.21 g, 31.5 mmol, 99%) was added dropwise at room temperature. The solution was stirred for 1 h at 50 °C in an oil bath. The solids were collected by filtration, washed with acetone and dried in vacuo to give N-[7-iodo-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]benzamide (8.73 g, 91 %, 90% purity) as a white solid. MS: m/z = 412.2 [M+H]+.
e. N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1,3]thiazolo[4,5-c]pyridin- 2-yl]benzamide
To a solution of N-[7-iodo-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]benzamide (6.00 g, 13.1 mmol, 90%) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (6.13 g, 27.7 mmol, 95%) in dioxane (200 mL) and water (40.00 mL) were added NaOH (2.90 g, 68.9 mmol, 95%) and Pd(dppf)Cl2* dichloromethane (1.20 g, 1.40 mmol, 95%). After stirring for 1 h at 100°C under a nitrogen atmosphere, the mixture was concentrated to dryness under vacuo. The residue was purified by silica gel chromatography with ethyl acetate/hexane (95:5). This resulted in 3.32 g (62%, 90% purity) of N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]benzamide as colorless solid. MS: m/z = 368.1 [M+H]+.
f. 7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1,3]thiazolo[4,5-c]pyridin-2- amine
To a stirred mixture of N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]benzamide (3.27 g, 8.00 mmol, 90%) in water/methanol (1 :1 , 300 mL) was added NaOH (3.36 g, 80.0 mmol, 95%) at room temperature under nitrogen atmosphere. The mixture was stirred for overnight at 90°C under nitrogen atmosphere and evaporated to dryness. The residue was taken up in water and extracted 3 times with dichloromethane (100 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel column chromatography, eluted with petrol ether/ethyl acetate (1 :1) to afford 7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-amine (1.50 g, 68%, 96% purity) as a light brownish solid. MS: m/z = 264.1 [M+H]+.
g. phenyl N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy- [1,3]thiazolo[4,5c]pyridin-2-yl]-N-(phenoxycarbonyl)carbamate
To a stirred solution of 7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-amine (600 mg, 2.19 mmol, 96%) and phenyl chloroformate (1.81 g,
11.0 mmol, 95%) in THF (50 mL) was added K2CO3 (1.59 g, 11.0 mmol, 95%) and pyridine (913 mg, 11.0 mmol, 95%) at room temperature under nitrogen
atmosphere. The mixture was stirred for 6 h at 50° and then after re-cooling to room temperature quenched by the addition of water (300 mL). The mixture was extracted 3 times with dichloromethane (200 mL), the combined organic layers were washed once with brine (200 mL), dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. This resulted in phenyl N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]-N-(phenoxycarbonyl)carbamate (1.00 g, 69%, 76% purity) as a light yellow solid. The crude product was used in the next step directly without further purification. MS: m/z = 504.1 [M+H]+.
h. N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1,3]thiazolo[4,5-c]pyridin- 2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide
To a mixture of phenyl N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]-N-(phenoxycarbonyl)carbamate (1.00 g, 1.52 mmol, 76.) and bis(7-oxa-2-azaspiro[4.5]decane), oxalic acid (1.19 g, 3.03 mmol, 95%) in THF (50 mL) was added diisopropylethyl amine (1.24 g, 9.09 mmol, 95%) at room temperature under nitrogen atmosphere. The mixture was stirred for 1 h at 60°. After re-cooling to room temperature, the mixture was extracted twice with dichloromethane (100 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel column chromatography, eluted with petrol ether/ethyl acetate (1 :1) to afford N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide (600 mg, 92%) as a white solid. HPLC: 99.9 % purity, RT = 1.17 min. MS: m/z = 431.1 [M+H]+. 1 H NMR (300 MHz, DMSO-d6) d 1 1.37 (s, 1 H), 7.95 (s, 1 H), 6.25 (s, 1 H), 4.30-4.29 (m, 2H), 3.99 (s, 3H), 3.89 (t, J=5.4Hz, 2H), 3.61-3.29 (m, 8H), 2.55-2.51 (m, 2H), 1.82-1.54 (m, 6H).
i. (5R)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin- 2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide 24
and (5S)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5- c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide 25
N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide (450 mg, 1.044 mmol, 1 equiv, 99.9%) was purified by chiral-preparative HPLC (Preparative HPLC-032, column: ChiralPak IA, 2*25cm, 5 mm; mobile phase, dichloromethane:ethanol (20:80); detector, UV). This resulted in (5R)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide (178 mg, 39%) as a white solid. HPLC: 99.7 % purity, RT (chiral) = 3.86 min, 100% ee. MS: m/z = 431.2 [M+H]+. 1 H NMR (400 MHz, DMSO-d6) d 1 1.36 (s, 1 H), 7.94 (s, 1 H), 6.24 (s, 1 H), 4.29-4.27 (m, 2H), 3.97 (s,3H), 3.88 (t, J=5.2 Hz, 2H), 3.51-3.19 (m, 8H), 2.55-2.50 (m, 2H), 1.83-1.53 (m, 6H) and (5S)-N-[7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-[1 ,3]thiazolo[4,5-c]pyridin-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide (171 mg, 38%) as a white solid. HPLC: 99.8 % purity, RT (chiral) = 5.23 min, 99.9% ee. MS: m/z = 431.2 [M+H]+. 1 H NMR (400 MHz, DMSO-d6) d 1 1.35 (s, 1 H), 7.94 (s, 1 H), 6.24 (s, 1 H), 4.29-4.28 (m, 2H), 3.99 (s, 3H), 3.88-3.85 (m, 2H), 3.61-3.29 (m, 8H), 2.55-2.50 (m,2H), 1.83-1.53 (m,6H).
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024028273&_cid=P10-MHPOFP-06905-1
AS ON OCT2025 4.511 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
……
//////////muvadenant, adenosine receptor antagonist, antineoplastic, 6LSF69F6A8, M1069 , M 1069
Lunresertib
Lunresertib
CAS 2719793-90-3
MF C18H20N4O2 MW 324.4 g/mol
(1P)-2-amino-1-(3-hydroxy-2,6-dimethylphenyl)-5,6-dimethyl1H-pyrrolo[2,3-b]pyridine-3-carboxamide
serine/ threonine kinase inhibitor, antineoplastic, N95U3A7N57, RP-6306, RP 6306
2-Amino-1-(3-hydroxy-2,6-dimethylphenyl)-5,6-dimethylpyrrolo[2,3-b]pyridine-3-carboxamide
Lunresertib is an investigational new drug that is being evaluated for the treatment of cancer. It is an oral small molecule inhibitor of PKMYT1, developed by Repare Therapeutics.[1] This drug targets cell cycle regulation in tumors with specific genetic alterations, including CCNE1 amplifications or FBXW7 and PPP2R1A loss of function mutations. It is currently in phase 1/2 clinical trials, both as monotherapy or in combination with camonsertib, an ATR inhibitor.[2]
Lunresertib is an orally bioavailable inhibitor of the human membrane-associated tyrosine– and threonine-specific cdc2-inhibitory kinase (PKMYT1), with potential antineoplastic activity. Upon oral administration, lunresertib targets, binds to and inhibits the activity of PKMYT1. This results in the inhibition of CDK1 phosphorylation, which may promote both premature mitosis and a prolonged mitotic arrest, and lead to the accumulation of unrepaired DNA damage and apoptosis in susceptible tumor cells, such as CCNE1-overexpressing tumor cells. PKMYT1 phosphorylates CDK1 specifically when CDK1 is complexed to cyclins, which blocks progression from G2 into mitosis.NCI Thesaurus (NCIt)
- Study of RP-6306 With FOLFIRI in Advanced Solid TumorsCTID: NCT05147350Phase: Phase 1Status: TerminatedDate: 2025-08-20
- Study of RP-6306 Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid TumorsCTID: NCT04855656Phase: Phase 1Status: RecruitingDate: 2025-08-06
- RP-6306 in Patients With Advanced CancerCTID: NCT05605509Phase: Phase 2Status: Active, not recruitingDate: 2025-07-14
- Study of RP-6306 With Gemcitabine in Advanced Solid TumorsCTID: NCT05147272Phase: Phase 1Status: TerminatedDate: 2025-06-17
- Liquid-biopsy Informed Platform Trial to Evaluate CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast CancerCTID: NCT05601440Phase: Phase 2Status: RecruitingDate: 2025-01-14
- Phase 1 Study of RP-6306 With Carboplatin and Paclitaxel in TP53 Ovarian and Uterine Cancer
- CTID: NCT06107868
- Phase: Phase 1
- Status: Active, not recruiting
- Date: 2024-03-22
PAT
- Compounds, Pharmaceutical Compositions, and Methods of Preparing and Using CompoundsPublication Number: JP-2023521633-APriority Date: 2020-04-01
- Compounds, pharmaceutical compositions, and methods of preparing compounds and of their usePublication Number: US-2023151014-A1Priority Date: 2020-04-01
- Methods of using myt1 inhibitorsPublication Number: US-2023158022-A1Priority Date: 2020-04-01
- Compounds, pharmaceutical compositions, and methods of preparing compounds and of their usePublication Number: EP-4126879-A1Priority Date: 2020-04-01
- Compounds, pharmaceutical compositions, and methods of preparing compounds and of their usePublication Number: IL-296934-APriority Date: 2020-04-01
- Compounds, pharmaceutical compositions, and methods of making the compounds and methods of using themPublication Number: KR-20230011279-APriority Date: 2020-04-01
- Compounds, pharmaceutical compositions and methods of making compounds and methods of their usePublication Number: CN-115916783-APriority Date: 2020-04-01
- Methods of using MYT1 inhibitorsPublication Number: JP-2023519430-APriority Date: 2020-04-01
- Methods of using myt1 inhibitorsPublication Number: WO-2021195782-A1Priority Date: 2020-04-01
- Compounds, pharmaceutical compositions, and methods of preparing compounds and of their usePublication Number: AU-2021250744-A1Priority Date: 2020-04-01
- Methods of using myt1 inhibitorsPublication Number: CA-3173955-A1Priority Date: 2020-04-01
- Methods of using MYT1 inhibitorsPublication Number: CN-115811976-APriority Date: 2020-04-01
- Methods of using myt1 inhibitorsPublication Number: EP-4125907-A1Priority Date: 2020-04-01
SYN
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021195781&_cid=P20-MHLE6P-37080-1
Step 9. To a suspension of 2-amino-1-(3-methoxy-2,6-dimethyl-phenyl)-5,6-dimethyl-pyrrolo[2,3-b]pyridine-3-carboxamide (2.22 g, 6.56 mmol, 77% purity) in DCM (25 mL) was added tribromoborane in DCM (1 M, 26 mmol, 26 mL) dropwise. The reaction mixture was stirred at RT for 45 min, then concentrated to dryness. The crude product was taken in DCM and placed in an ice bath and MeOH was added carefully (exotherm). The mixture was concentrated to dryness then co-evaporated twice with MeOH. The residue was triturated with saturated aqueous NaHCO3. The solids were collected by filtration on a Buchner funnel, washed with H2O and air-dried. The still wet solid was dissolved in DCM/MeOH, concentrated to dryness and triturated in 20% MeOH/DCM (50 mL). The solid was collected by filtration, washed with 20% MeOH/DCM, air-dried then dried in vacuo to afford 2-amino-1-(3-hydroxy-2,6-dimethyl-phenyl)-5,6-dimethyl-pyrrolo[2,3-b]pyridine-3-carboxamide (1.60g, 75% yield) as a light beige solid. MS: [M+1]: 325.1. A different batch was purified by preparative HPLC to yield 2-amino-1-(3-hydroxy-2,6-dimethyl-phenyl)-5,6-dimethyl-pyrrolo[2,3-b]pyridine-3-carboxamide (63% yield) as an off-white fluffy solid.
1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 7.82 (s, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.90 (d, J =
8.2 Hz, 1H), 6.71 (br s, 2H), 6.64 (br s, 2H), 2.26 (s, 3H), 2.23 (s, 3H), 1.74 (s, 3H), 1.65 (s, 3H). MS: [M+1]: 325.1.
Chiral SFC separation of Compound 181 (1.60g, 4.93 mmol) (Instrument: Waters Prep 100 SFC-MS; Column: Phenomenex Lux Cellulose-2, 30 x 250 mm, 5 μm; Conditions: isocratic at 55% IPA + 10mM Ammonium Formate with 45% CO2 ; Flow Rate: 70 mL/min) provided
Compound 182 and Compound 183.
Compound 182 from SFC separation of 181. Peak 1 (retention time 3.94 min, 99.86%): (S)-2- amino-1-(3-hydroxy-2,6-dimethyl-phenyl)-5,6-dimethyl-pyrrolo[2,3-b]pyridine-3-carboxamide (381 mg) was obtained as an off white fluffy solid. 1H NMR (400 MHz, DMSO-d6) δ 9.50 (s, 1H), 7.83 (s, 1 H), 7.05 (d, J = 8.3 Hz, 1H), 6.90 (d, J = 8.3 Hz, 1H), 6.72 (s, 2H), 6.65 (s, 2H), 2.26 (s, 3H), 2.24 (s, 3H), 1.74 (s, 3H), 1.65 (s, 3H). MS: [M+1]: 325.1.
Compound 183 from SFC separation of 181. Peak 2 (retention time 4.35 min, 98.09%): (R)-2- amino-1-(3-hydroxy-2,6-dimethyl-phenyl)-5,6-dimethyl-pyrrolo[2,3-b]pyridine-3-carboxamide (495 mg) was obtained as an off white fluffy solid. 1H NMR (400 MHz, DMSO-d6) δ 9.50 (s, 1H), 7.83 (s, 1 H), 7.05 (d, J = 8.2 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.72 (s, 2H), 6.66 (s, 2H), 2.26 (s, 3H), 2.24 (s, 3H), 1.74 (s, 3H), 1.65 (s, 3H). MS: [M+1]: 325.1.
SYN
https://pubs.acs.org/doi/full/10.1021/acs.oprd.4c00493
REF
- The Science and Art of Structure-Based Virtual ScreeningPublication Name: ACS Medicinal Chemistry LettersPublication Date: 2024-03-25PMCID: PMC11017385PMID: 38628791DOI: 10.1021/acsmedchemlett.4c00093
- Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306Publication Name: Journal of Medicinal ChemistryPublication Date: 2022-07-26PMCID: PMC9837800PMID: 35880755DOI: 10.1021/acs.jmedchem.2c00552
- CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibitionPublication Name: NaturePublication Date: 2022-04-20PMCID: PMC9046089PMID: 35444283DOI: 10.1038/s41586-022-04638-9
- Contributions in the domain of cancer research: Review¶Negative regulators of cyclin-dependent kinases and their roles in cancersPublication Name: Cellular and molecular life sciences : CMLSPublication Date: 2001-11PMCID: PMC11337304PMID: 11766887DOI: 10.1007/pl00000826
AS ON OCT2025 4.511 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
……
| Clinical data | |
|---|---|
| Other names | RP-6306 |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2719793-90-3 |
| PubChem CID | 156869388 |
| ChemSpider | 115008046 |
| UNII | N95U3A7N57 |
| KEGG | D12736 |
| ChEMBL | ChEMBL5199076 |
| Chemical and physical data | |
| Formula | C18H20N4O2 |
| Molar mass | 324.384 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
References
- Szychowski J, Papp R, Dietrich E, Liu B, Vallée F, Leclaire ME, et al. (August 2022). “Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306”. Journal of Medicinal Chemistry. 65 (15): 10251–10284. doi:10.1021/acs.jmedchem.2c00552. PMC 9837800. PMID 35880755.
- Previtali V, Bagnolini G, Ciamarone A, Ferrandi G, Rinaldi F, Myers SH, et al. (July 2024). “New Horizons of Synthetic Lethality in Cancer: Current Development and Future Perspectives”. Journal of Medicinal Chemistry. 67 (14): 11488–11521. doi:10.1021/acs.jmedchem.4c00113. PMC 11284803. PMID 38955347.
///////lunresertib, Serine/ threonine kinase inhibitor, antineoplastic, N95U3A7N57, RP-6306, RP 6306
Lunbotinib
Lunbotinib
CAS 2479961-46-9
MF C28H28FN11 MW537.6 g/mol
2-[6-(6-{[6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl]-6-methyl-N-(5-methyl1H-pyrazol-3-yl)pyrimidin-4-amine
tyrosine kinase inhibitor, antineoplastic, KL3T9ZU6HQ
- 2-(6-(6-((6-(4-fluoropyrazol-1-yl)pyridin-3-yl)methyl)-3,6-diazabicyclo(3.1.1)heptan-3-yl)pyridin-3-yl)-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine
- 2-[6-[6-[[6-(4-fluoropyrazol-1-yl)pyridin-3-yl]methyl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]pyridin-3-yl]-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine
Lunbotinib is an orally bioavailable selective inhibitor of the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, lunbotinib selectively binds to various RET fusions and mutations, including solvent front resistance mutations, and inhibits the activity of RET. This results in an inhibition of cell growth of tumors that exhibit increased RET activity due to these fusions and mutations. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types. Dysregulated RET activity plays a key role in the development and progression of certain cancers. Lunbotinib is able to penetrate the blood-brain barrier (BBB) and may also be able to overcome resistance mechanisms to first generation selective RET inhibitors (SRIs).
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020168939&_cid=P12-MHKH7H-14851-1
Example 6: 2-(6-(6-((6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-yl)pyridin-3-yl)-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (Compound 17)
Step 1: Preparation of 6-(4-fluoro-1H-pyrazol-1-yl)nicotinaldehyde (compound 17a)
[0396]Compound 8c (2.0 g), 91a hydrochloride (1.58 g), and potassium carbonate (4.45 g) were sequentially added to DMF (15 mL), and the mixture was heated to 80 °C and stirred for 14 h. The reaction mixture was cooled to room temperature, diluted with water (100 mL), and extracted with DCM (50 mL x 2). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography (PE:EA = 10:1) to give compound 17a (0.81 g). MS m/z (ESI): 192.1 [M+H]
[0397]Step 2: Preparation of 2-(6-(6-((6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-yl)pyridin-3-yl)-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (compound 17)
[0398]1 g of trifluoroacetate (22.82 mg) and compound 17a (27.47 mg) were added to methanol (1.0 mL), followed by the sequential addition of triethylamine (4.45 mg) and sodium cyanoborohydride (13.86 mg), and the reaction was carried out at room temperature for 14 h. After the reaction was completed, the reaction solution was concentrated to dryness under reduced pressure and purified by Prep-HPLC to obtain compound 17 (7.0 mg). MS m/z (ESI): 538.3 [M+H]
[0399]
1H NMR(400MHz,DMSO-d 6)δ11.98(s,1H),9.66(s,1H),9.12(d,J＝2.16Hz,1H),8.67(dd,J＝4.54,0.64Hz,1H),8.43(dd,J＝8.94,2.28Hz,1H),8.41(d,J＝1.68,1H),7.98(dd,J＝8.48Hz,2.12 1H),7.92(d,J＝4.28,1H),7.87(d,J＝8.4,1H),6.78(d,J＝9.0Hz,2H),6.31(br,1H),3.78-3.71(m,4H),3.68-3.52(m,4H),2.59-2.52(m,1H),2.33(s,3H),2.25(s,3H),1.60(d,J＝8.36Hz,1H).
PAT
- Heterocyclic compound, pharmaceutical composition comprising same, preparation method therefor, and use thereofPublication Number: US-2022144847-A1Priority Date: 2019-02-19
- Heterocyclic compounds, pharmaceutical compositions containing the same and preparation methods and uses thereofPublication Number: CN-113316578-BPriority Date: 2019-02-19Grant Date: 2023-10-31
- Heterocyclic compounds, pharmaceutical compositions containing the same and preparation methods and uses thereofPublication Number: CN-117263945-APriority Date: 2019-02-19
- Heterocyclic compounds, pharmaceutical compositions containing the same and preparation methods and uses thereofPublication Number: CN-117327078-APriority Date: 2019-02-19
- Heterocyclic compounds, pharmaceutical compositions containing same, methods for their preparation and usePublication Number: JP-7615056-B2Priority Date: 2019-02-19Grant Date: 2025-01-16
- Salt and crystal form of pyrimidine compound, and preparation methods thereforPublication Number: US-2023295174-A1Priority Date: 2020-07-28
- Heterocyclic compound, pharmaceutical composition comprising same, preparation method therefor, and use thereofPublication Number: WO-2020168939-A1Priority Date: 2019-02-19
- Heterocyclic compounds, pharmaceutical compositions containing the same, and preparation methods and uses thereofPublication Number: CN-113316578-APriority Date: 2019-02-19
- Heterocyclic compound, pharmaceutical composition comprising same, preparation method therefor, and use thereofPublication Number: EP-3929198-A1Priority Date: 2019-02-19
- Heterocyclic compounds, drug compositions containing them, methods of their manufacture and usePublication Number: JP-2022521859-APriority Date: 2019-02-19
- Use of heterocyclic compound for treating diseases related to ret genetic change and method thereforPublication Number: WO-2024240017-A1Priority Date: 2023-05-19
- Uses and methods of heterocyclic compounds for treating diseases associated with kinase resistance mutationsPublication Number: CN-116801882-APriority Date: 2021-03-24
- Use of heterocyclic compound in treating diseases related to kinase drug-resistant mutation and method thereforPublication Number: EP-4316490-A1Priority Date: 2021-03-24
- Salt and crystal form of pyrimidine compound, and preparation methods thereforPublication Number: EP-4190781-A1Priority Date: 2020-07-28
- Salts, crystal forms of pyrimidine compounds and methods for their preparationPublication Number: JP-2023535361-APriority Date: 2020-07-28
AS ON OCT2025 4.511 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
……
//////////Lunbotinib, tyrosine kinase inhibitor, antineoplastic, KL3T9ZU6HQ
Lirodegimod
Lirodegimod
CAS 2502186-79-8
MF C60H74ClN10O14PS, MW 1257.79
[2-[[(5S,8S,10aR)-3-acetyl-8-[[(2S)-5-amino-1-[2-chloro-3-[4-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-4-oxobutyl]phenoxy]-5-oxopentan-2-yl]carbamoyl]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-5-yl]carbamoyl]-1H-indole-5-carbonyl]phosphonic acid
KT 333, KT333, ANTINEOPLASTIC, Fast Track (United States), Orphan Drug (United States), 4Q6ZHJ2MNA
Lirodegimod is a small molecule drug. The usage of the INN stem ‘-imod’ in the name indicates that Lirodegimod is a immunomodulator, both stimulant/suppressive and stimulant. Lirodegimod has a monoisotopic molecular weight of 1256.45 Da.
Safety, PK, PD, Clinical Activity of KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, Solid Tumors
CTID: NCT05225584
Phase: Phase 1
Status: Completed
Date: 2025-03-19
PAT
- Stat3 degraders and uses thereofPublication Number: US-2023212201-A1Priority Date: 2021-12-11
- Stat3 degraders and uses thereofPublication Number: US-2025019388-A1Priority Date: 2021-12-11
- Stat degraders and uses thereofPublication Number: US-2024016942-A1Priority Date: 2020-03-17
- Stat degraders and uses thereofPublication Number: WO-2020206424-A1Priority Date: 2019-04-05
- Stat degraders and uses thereofPublication Number: US-11746120-B2Priority Date: 2019-04-05Grant Date: 2023-09-05
AS ON OCT2025 4.511 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
……
///////////Lirodegimod, KT 333, KT333, ANTINEOPLASTIC, Fast Track, Orphan Drug, 4Q6ZHJ2MNA
Iodofalan (131I)
Iodofalan (131I)
CAS 76641-05-9
MFC9H10131INO2
Molecular FormulaC9H10INO2
Molecular Weight295.09
4-(131I)iodo-L-phenylalanine
(2S)-2-amino-3-(4-iodophenyl)propanoic acid
radiopharmaceutical, antineoplastic, Phase 2, Glioblastoma, 606VTF676Y, 131I-TLX-101, ACD 101
- 4-Iodophenylalanine I-131
- 4-(131I)Iodo-L-phenylalanine
- 4-Iodo-L-phenylalanine-131I
- ACD-101
- L-Phenylalanine, 4-(iodo-131I)-
- OriginatorTherapeia
- DeveloperTelix Pharmaceuticals; Therapeia
- ClassAmino acids; Antineoplastics; Radioisotopes; Radiopharmaceutical diagnostics; Radiopharmaceuticals; Small molecules
- Mechanism of ActionApoptosis stimulants; Positron-emission tomography enhancers
- Orphan Drug StatusYes – Glioblastoma
- Phase IIGlioblastoma
- 14 Oct 2025Telix Pharmaceuticals receives IND approval for TLX 101 in Glioblastoma
- 27 Jul 2025Telix Pharmaceuticals plans a phase III IPAX BrIGHT trial for Glioblastoma (Monotherapy, Combination therapy, Recurrent, Second-line therapy or greater) in Australia(IV) (NCT07100730)(EudraCT2025-521785-10) in September 2025
- 16 Apr 2025Telix has submitted for ethics approval a registration-enabling study of TLX101 in recurrent glioblastoma.
Iodofalan (131I) is a radiopharmaceutical that has garnered significant attention in oncological research due to its targeted therapeutic potential. This compound, which includes the radioactive isotope Iodine-131, has been explored for its efficacy in treating certain types of cancers, particularly those associated with the thyroid. Various research institutions worldwide have been studying Iodofalan (131I) to better understand its clinical benefits, optimize its usage, and minimize potential side effects. As a drug type, Iodofalan (131I) is categorized as a targeted radiopharmaceutical therapy, which leverages the properties of radioactive isotopes to destroy cancer cells with precision. Currently, its primary indications include differentiated thyroid cancer and non-resectable metastatic thyroid cancer, among other investigational uses.
Iodofalan (131I) Mechanism of Action
The mechanism of action for Iodofalan (131I) centers on the properties of Iodine-131, a beta-emitting isotope. When administered, Iodofalan (131I) is selectively absorbed by thyroid cells. This selectivity is due to the thyroid gland’s natural ability to uptake iodine, a key element required for the production of thyroid hormones. Cancerous thyroid tissues retain this ability, making them ideal targets for Iodofalan (131I) therapy.
Once absorbed by the thyroid cancer cells, the radioactive decay of Iodine-131 begins. This decay process emits beta particles, which possess sufficient energy to destroy nearby cells. The radiation from these beta particles causes direct DNA damage, leading to cell death. Additionally, the gamma radiation emitted by Iodine-131 can be used diagnostically to track the distribution and uptake of the compound in the body via imaging techniques such as SPECT (Single Photon Emission Computed Tomography).
The dual role of Iodofalan (131I) in both treatment and diagnostic contexts underscores its importance in managing thyroid cancers. By delivering a localized radiation dose to thyroid cancer cells, Iodofalan (131I) minimizes damage to surrounding healthy tissues, which is a significant advantage over traditional external beam radiotherapy.
What is the indication of Iodofalan (131I)?
The primary indication for Iodofalan (131I) is the treatment of differentiated thyroid cancer, a category that includes papillary and follicular thyroid cancers. These subtypes are characterized by their ability to absorb iodine, making them particularly amenable to radioiodine therapy. Iodofalan (131I) is typically used in cases where the thyroid cancer is not amenable to surgical removal or has metastasized to other parts of the body. In such scenarios, the radiopharmaceutical offers a non-invasive therapeutic option that can target and destroy cancer cells even in distant metastatic sites.
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US42129729&_cid=P21-MHE8B5-15309-1
EXAMPLE 1
EXAMPLE 2
General synthesis of 3,4-[124I]iodo-L-phenylalanine (m, p-IPA-124), 3,4-[125I]iodo-L-phenylalanine (m,p-IPA-125) and 3,4-[131I]iodo-L-phenylalanine (m,p-IPA-131) by non-isotopic radioiodo-debromination
PAT
- Pharmaceutical combinations and uses thereofPublication Number: US-2024197715-A1Priority Date: 2022-11-18
- Pharmaceutical combinations and uses thereofPublication Number: WO-2024105610-A1Priority Date: 2022-11-18
- Iodine-labeled homoglutamic acid and glutamic acid derivativesPublication Number: US-2013034497-A1Priority Date: 2009-11-17
- MALIGNAS NEOPLASIAS THERAPY.Publication Number: ES-2341575-T3Priority Date: 2005-11-25Grant Date: 2010-06-22
- Therapy of malignant neoplasiasPublication Number: US-2007128108-A1Priority Date: 2005-11-18
- Therapy of malignant neoplasias
- Publication Number: US-9682158-B2
- Priority Date: 2005-11-18
- Grant Date: 2017-06-20
AS ON OCT2025 4.511 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
……
//////////Iodofalan (131I), radiopharmaceutical, antineoplastic, Phase 2, Glioblastoma, 606VTF676Y, 131I-TLX-101, ACD 101
Inlexisertib
Inlexisertib
CAS 2543673-19-2
MF C26H36F3N7O2, 535.62
4-(3-((2-((2-ethyl-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)propyl)-1,4-oxazepan-5-one
4-[3-[[2-[2-ethyl-4-(4-methylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]propyl]-1,4-oxazepan-5-one
serine/ threonine kinase inhibitor, antineoplastic, DCC 3116, JM2ZTM8S7S
Inlexisertib is an orally bioavailable inhibitor of the serine/threonine-protein kinase ULK 1 and 2, with potential antineoplastic activity. Upon oral administration, inlexisertib targets and binds to ULK1/2. This inhibits cancer autophagy, which mutant RAS cancer cells use for their survival, and results in tumor cell death. ULK1/2 mediates the autophagocytotic process and is often upregulated in cancers, especially in mutant RAS cancers. Autophagy plays a key role in a tumor cell proliferation and survival, and mediates tumor cell resistance.
- A Study of Inlexisertib (DCC-3116) in Combination With Anticancer Therapies in Participants With Advanced MalignanciesCTID: NCT05957367Phase: Phase 1/Phase 2Status: RecruitingDate: 2025-06-05
- A Phase 1/2 Study of Inlexisertib (DCC-3116) in Patients With RAS/MAPK Pathway Mutant Solid TumorsCTID: NCT04892017Phase: Phase 1/Phase 2Status: RecruitingDate: 2025-05-06
SYN
https://patents.google.com/patent/US11530206B2/en
PAT
Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereof
Publication Number: JP-7593947-B2
Priority Date: 2019-05-10
Grant Date: 2024-12-03
- PHENYLAMINOPYRIMIDINE AMIDE INHIBITORS OF AUTOPHAGY AND METHODS OF THEIR APPLICATIONPublication Number: HR-P20231730-T1Priority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: US-12071432-B2Priority Date: 2019-05-10Grant Date: 2024-08-27
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: CN-118878519-APriority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: CN-118878520-APriority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: CN-118930524-APriority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: AU-2020275392-B2Priority Date: 2019-05-10Grant Date: 2023-09-14
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: CN-114127057-BPriority Date: 2019-05-10Grant Date: 2024-07-12
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: EP-3966207-B1Priority Date: 2019-05-10Grant Date: 2023-11-01
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: EP-4342469-A2Priority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: ES-2966807-T3Priority Date: 2019-05-10Grant Date: 2024-04-24
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: EP-3966207-A1Priority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: KR-20220008873-APriority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitor and how to use itPublication Number: JP-2022531801-APriority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: US-11530206-B2Priority Date: 2019-05-10Grant Date: 2022-12-20
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: US-2023039712-A1Priority Date: 2019-05-10
- Combination of dcc-3116 and mapkap pathway inhibitors for use in the treatment of cancerPublication Number: WO-2024050351-A1Priority Date: 2022-09-02
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: US-2020354352-A1Priority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: WO-2020231806-A1Priority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereofPublication Number: AU-2020275392-A1Priority Date: 2019-05-10
- Phenylaminopyrimidine amide autophagy inhibitor and method of usePublication Number: CN-114127057-APriority Date: 2019-05-10
PAT
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020231806&_cid=P12-MHCSWS-98394-1
AS ON JUNE2025 4.45 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
……
/////////Inlexisertib, serine/ threonine kinase inhibitor, antineoplastic, DCC 3116, JM2ZTM8S7S
Icovamenib
Icovamenib
CAS 2448172-22-1
MF C31H34N8O3 MW 566.7 g/mol
N-{4-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl}-4-{[(3R)-3-(prop-2-enamido) piperidin-1-yl]methyl}pyridine-2-carboxamide
N-[4-(4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl]-4-[[(3R)-3-(prop-2-enoylamino)piperidin-1-yl]methyl]pyridine-2-carboxamide
menin-MLL (mixed-lineage leukemia) protein interaction inhibitor,
antineoplastic, BMF-219, BMF 219, 2Z737MY35A, Menin-MLL inhibitor 21
Icovamenib is an investigational irreversible covalent inhibitor of menin. It is developed by Biomea Fusion for diabetes, lymphoma, leukemia, and multiple myeloma.[1][2][3]
Icovamenib is an orally bioavailable, irriversible inhibitor of menin, an essential co-factor of oncogenic menin-mixed lineage leukemia (MLL; myeloid/lymphoid leukemia; KMT2A) fusion proteins, with potential antineoplastic activity. Upon oral administration, icovamenib specifically targets and binds to menin, thereby preventing the interaction between the two proteins menin and MLL and the formation of the menin-MLL complex. This reduces the expression of downstream target genes, such as MYC and Bcl2, and results in an inhibition of the proliferation of MLL-rearranged tumor cells. Menin, an essential transcriptional regulator, plays a key role in oncogenic signaling in cancers driven by oncogenic MLL-fusions.
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US299042443&_cid=P20-MH9YDY-31032-1
Example 9
Synthesis of Compound 10
Compound 10
General Procedure for Preparation of Intermediate 2
| 1H NMR: CDCl 3 400 MHz 8.80 (d, J=4.85 Hz, 1H), 8.15 (d, J=0.66 Hz, 1H), 7.53 (dt, J=4.91, 0.85 Hz, 1H), 5.27-5.34 (m, 2H), 4.00-4.08 (m, 3H), 3.11 (s, 3H) |
General Procedure for Preparation of Intermediate 5—
| To a solution of Intermediate 4 (1.50 g, 4.29 mmol, 1 eq) in THF (7.00 mL) was added LiOH.H 2O (540.3 mg, 12.8 mmol, 3 eq) in H 2O (7.00 mL). The mixture was stirred at 25° C. for 3 h. TLC (Dichloromethane:Methanol=10:1, R f=0) showed the reaction was complete. The mixture was poured into H 2O (20.0 mL) and extracted with DCM (10.0 mL×3). Then the organic phases dried over Na 2SO 4, filtered and concentrated under vacuum. The crude without purification. Give the Intermediate 5 (1.20 g, crude) as a yellow solid. |
General Procedure for Preparation of Intermediate 6—
| To a solution of Intermediate 5 (0.80 g, 2.39 mmol, 1 eq), Intermediate 3A (704.4 mg, 2.39 mmol, 1 eq), TEA (1.69 g, 16.7 mmol, 2.32 mL, 7 eq) in DCM (10.0 mL) was added HATU (1.36 g, 3.58 mmol, 1.5 eq). The mixture was stirred at 20° C. for 12 h. LCMS showed the reaction was complete. The mixture was poured into H 2O (40.0 mL) and extracted with DCM (20.0 mL×3). Then the organic phases were washed with brine (50.0 mL) dried over Na 2SO 4, filtered and concentrated under vacuum. The crude for next step without purification. Give the Intermediate 6 (0.60 g, crude) as a yellow solid. |
General Procedure for Preparation of Intermediate 7—
| To a solution of Intermediate 6 (0.50 g, 816.0 umol, 1 eq) in MeOH (5.00 mL) was added HCl/MeOH (4 M, 5.00 mL, 24.51 eq). The mixture was stirred at 20° C. for 12 h. LCMS showed the reaction was complete. The mixture was concentrated under vacuum. The crude for next step without purification. Give the Intermediate 7 (0.50 g, crude, HCl) as a yellow solid. |
General Procedure for Preparation of Compound 10—
| To a solution of Intermediate 3 (0.50 g, 910.6 umol, 1 eq, HCl) in DMF (10.0 mL) was added TEA (645.0 mg, 6.37 mmol, 887.2 uL, 7 eq) and prop-2-enoyl chloride (82.4 mg, 910.6 umol, 74.2 uL, 1 eq). Then the mixture was stirred at 20° C. for 12 h. LCMS showed the reaction was complete. The mixture was poured into H 2O (50.0 mL), then was filtered and filter cake was concentrated in vacuum. The crude product was purified by reversed-phase HPLC (column: Phenomenex Luna C18 200*40 mm*10 um; mobile phase: [water(0.05% HCl)-ACN]; B %: 10%-30%, 10 min) and (column: Xtimate C18 150*25 mm*5 um; mobile phase: [water(10 mM NH 4HCO 3)-ACN]; B %: 30%-60%, 10 min). Give the Intermediate Compound 10 (20.0 mg, 35.0 umol, 3.85% yield, 99.3% purity) as a yellow solid. |
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024172911&_cid=P20-MH9YNT-37455-1
PAT
- Substituted pyridines as irreversible inhibitors of menin-MLL interactionPublication Number: US-11702421-B2Priority Date: 2018-12-31Grant Date: 2023-07-18
- Irreversible inhibitors of menin-mll interactionPublication Number: US-2023227458-A1Priority Date: 2018-12-31
- N-[4-[4-(4-MORPHOLINYL)-7H-PYRROLO[2,3-d]PYRIMIDIN-6-YL]PHENYL]-4-[[3(R)-[(1-OXO-2-PROPEN-1-YL)AMINO]-1-PIPERIDINYL]METHYL]-2-PYRIDINE CARBOXAMIDE AND USES THEREOFPublication Number: US-2024376112-A1Priority Date: 2018-12-31
- Covalent inhibitors of menin-mll interaction for diabetes mellitusPublication Number: WO-2023018825-A1Priority Date: 2021-08-11
- Covalent inhibitors of Mennin-MLL interaction for diabetesPublication Number: CN-118076357-APriority Date: 2021-08-11
- Irreversible inhibitors of menin-mll interactionPublication Number: US-2020223853-A1Priority Date: 2018-12-31
- Substituted pyridines as irreversible inhibitors of menin-MLL interactionPublication Number: US-11084825-B2Priority Date: 2018-12-31Grant Date: 2021-08-10
- Irreversible inhibitors of menin-mll interactionPublication Number: US-2022169627-A1Priority Date: 2018-12-31
- Crystalline forms of an irreversible inhibitor of menin-mll interactionPublication Number: US-2023086137-A1Priority Date: 2021-08-20
- Crystalline form of n-[4-[4-(4-morpholinyl)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-4-[[3(r)-[(1-oxo -2-propen-1-yl)amino]-1-piperidinyl]methyl]-2-pyridinecarboxamide, an irreversible menin-mll inhibitor for the treatment of cancerPublication Number: EP-4387972-A1Priority Date: 2021-08-20
- Crystalline forms of N-[4-[4-(4-morpholinyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-4-[[3(r)-[(1-oxo-2-propen-1-yl)amino]-1-piperidinyl]methyl]-2-pyridinecarboxamide as an irreversible inhibitor of menin-MLL interactionPublication Number: US-12018032-B2Priority Date: 2021-08-20Grant Date: 2024-06-25
- Crystalline form of n-[4-[4-(4-morpholinyl)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-4-[[3(r)-[(1-oxo -2-propen-1-yl)amino]-1-piperidinyl]methyl]-2-pyridinecarboxamide, an irreversible menin-mll inhibitor for the treatment of cancerPublication Number: WO-2023022912-A1Priority Date: 2021-08-20
- Crystalline forms of an irreversible inhibitor of menin-mll interactionPublication Number: US-2024343731-A1Priority Date: 2021-08-20
- Synthetic methods for preparing a pyridinecarboxamide compoundPublication Number: WO-2024011450-A1Priority Date: 2022-07-13
- Menin-mll inhibitors and compositions for proliferation of beta cellsPublication Number: WO-2024006391-A1Priority Date: 2022-06-28
- Flt3 combination therapy for cancer and compositions thereforPublication Number: WO-2023225005-A1Priority Date: 2022-05-17
- Treatment of cancer with menin inhibitors and immuno-oncology agentsPublication Number: WO-2023172925-A1Priority Date: 2022-03-08
- Treatment of hematological malignancies with menin inhibitors and p-glycoprotein inhibitorsPublication Number: WO-2023150635-A1Priority Date: 2022-02-04
- Crystalline forms of N[4[4-(4-Morpholinyl)-7H-Pyrrolo[2-3-D]Pyrimidin-6-yl]Phenyl]-4-[[3(R)-[(1-Oxo-2-Protein-1-yl)Amino]-1-Piperidinyl]Methyl]2-Pyridinecarboxamide]Publication Number: US-12215113-B2Priority Date: 2023-01-18Grant Date: 2025-02-04
- CRYSTALLINE FORMS OF N-[4-[4-(4-MORPHOLINYL)-7H-PYRROLO[2,3-d]PYRIMIDIN-6-YL]PHENYL]-4-[[3(R)-[(1-OXO-2-PROPEN-1-YL)AMINO]-1-PIPERIDINYL]METHYL]-2-PYRIDINECARBOXAMIDE AS IRREVERSIBLE INHIBITORS OF MENIN-MLL INTERACTIONPublication Number: US-2024417404-A1Priority Date: 2023-01-18
- Crystalline forms of n-[4-[4-(4-morpholinyl)-7h-pyrrolo[2,3-d]pyrimidin-6- yl]phenyl]-4-[[3(r)-[(l-oxo-2-propen-l-yl)amino]-l-piperidinyl]methyl]-2-pyridinecarboxamide as a covalent inhibitor of menin-mll interactionPublication Number: WO-2024155710-A1Priority Date: 2023-01-18
- Crystalline forms of n-[4-[4-(4-morpholinyl)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-4-[[3(r)-[(l-oxo-2-propen-l-yl)amino]-l-piperidinyl]methyl]-2- pyridinecarboxamide as a covalentinhibitor of menin-mll interactionPublication Number: WO-2024155719-A1Priority Date: 2023-01-18
- Combinations of lsd1 inhibitors and menin inhibitors for treating cancerPublication Number: WO-2024110649-A1Priority Date: 2022-11-24
AS ON JUNE2025 4.45 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
- Rodriguez, Jose E.; Abitbol, Alexander; Abuzgaya, Fathi; Perez, Cesar; Mourya, Sanchita; Munneke, Brian; Morris, Stephan W.; Butler, Thomas (20 June 2023). “91-LB: COVALENT-111, a Phase 1/2 Trial of BMF-219, a Covalent Menin Inhibitor, in Patients with Type 2 Diabetes Mellitus—Preliminary Results”. Diabetes. 72 (Supplement_1) 91-LB. doi:10.2337/db23-91-LB. S2CID 259444592.
- Ravandi-Kashani, F.; Kishtagari, A.; Carraway, H.; Schiller, G.; Curran, E.; Yadav, B.; Cacovean, A.; Morris, S.; Butler, T.; Lancet, J. (23 June 2022). “P587: Covalent-101: A Phase 1 Study of BMF-219, A Novel Oral Irreversible Menin Inhibitor, in Patients with Relapsed/Refractory Acute Leukemia, Diffuse Large B-Cell Lymphoma, and Multiple Myeloma”. HemaSphere. 6: 486–487. doi:10.1097/01.HS9.0000845236.32931.83.
- Somanath, Priyanka; Lu, Daniel; Law, Brian; Archer, Tenley C.; Cacovean, Alexandru; Palmer, James T.; Kinoshita, Taisei; Butler, Thomas (5 November 2021). “Novel Irreversible Menin Inhibitor, BMF-219, Shows Potent Single Agent Activity in Clinically Relevant DLBCL Cells”. Blood. 138 (Supplement 1): 4318. doi:10.1182/blood-2021-148045.
| Clinical data | |
|---|---|
| Other names | BMF-219 |
| Legal status | |
| Legal status | Investigational |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2448172-22-1 |
| PubChem CID | 154988914 |
| ChemSpider | 115037287 |
| UNII | 2Z737MY35A |
| Chemical and physical data | |
| Formula | C31H34N8O3 |
| Molar mass | 566.666 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
/////////Icovamenib, antineoplastic, BMF-219, BMF 219, 2Z737MY35A, Menin-MLL inhibitor 21
Ibrilatazar
Ibrilatazar
CAS 57818-44-7
MF C18H32O3 MW 296.4 g/mol
rac-(2R)-(9Z,12Z)-2-hydroxyoctadeca-9,12-dienoic acid
(9Z,12Z)-2-hydroxyoctadeca-9,12-dienoic acid
peroxisome proliferator activated receptor (PPAR) alpha and gamma agonist, antineoplastic, ABILITY PHARMA, ABTL 0812, alpha-Hydroxylinoleic acid, ABTL0812
- alpha-Hydroxylinoleic acid
- ABTL0812
- 2-hydroxylinoleic acid
| Ingredient | UNII | CAS | InChI Key |
|---|---|---|---|
| ABTL-0812 Sodium | X1840C8161 | Not Available | VFXKYDDSDQXKLC-NBTZWHCOSA-M |
Ibrilatazar also known as α-hydroxylinoleic acid is a small-molecule, experimental cancer drug being developed by Ability Pharmaceuticals.[1]
Ibrilatazar is an orally bioavailable, lipid analogue and inhibitor of raptor-mammalian target of rapamycin (mTOR) (mTOR complex 1; mTORC1), rictor-mTOR (mTOR complex 2; mTORC2) and dihydrofolate reductase (DHFR) with potential antineoplastic activity. Upon oral administration, ibrilatazar binds to and inhibits both mTORC1 and mTORC2, which may result in apoptosis and a decrease in proliferation in mTORC1/2-expressing tumor cells. mTOR is a serine/threonine kinase that is upregulated in some tumors; it plays an important role in the PI3K/Akt/mTOR signaling pathway which is often deregulated in cancer cells. In addition, ibrilatazar inhibits DHFR, an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, thereby blocking tetrahydrofolate synthesis, and resulting in both the depletion of nucleotide precursors and the inhibition of DNA, RNA and protein synthesis. This induces autophagy-induced cell death and further inhibition of cell proliferation.
- A Study of ABTL0812 in Pancreatic CancerCTID: NCT03417921Phase: Phase 1/Phase 2Status: SuspendedDate: 2024-07-31
- ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic StudyCTID: NCT04431258Phase: Phase 1/Phase 2Status: CompletedDate: 2024-03-18
- Phase I/Ib Clinical Trial of ABTL0812 in Advanced Cancer PatientsCTID: NCT02201823Phase: Phase 1Status: CompletedDate: 2015-07-02
- Microbiological production method of γ- and δ-lactonesPublication Number: JP-H03187387-APriority Date: 1989-08-04
- Process for the microbiological production of gamma- and delta-lactonesPublication Number: US-5168054-APriority Date: 1989-08-04Grant Date: 1992-12-01
- Degradation control of environmentally degradable disposable materialsPublication Number: US-2002123546-A1Priority Date: 1988-08-08
- Degradation control of environmentally degradable disposable materialsPublication Number: US-6323307-B1Priority Date: 1988-08-08Grant Date: 2001-11-27
- Degradation control of environmentally degradable disposable materialsPublication Number: US-6740731-B2Priority Date: 1988-08-08Grant Date: 2004-05-25
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=US38087288&_cid=P12-MH8IQK-97634-1
AS ON JUNE2025 4.45 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
……
History
In 2015, Ability announced that it had received orphan drug designation (ODD) for pediatric cancer neuroblastoma from the European Medical Agency (EMA) and the US Food and Drug Administration (FDA).[1] Also in 2016 a preclinical study confirmed that ABTL0812 was well tolerated.[2] In December 2016 the company announced Ibrilatazar has received an Orphan Drug Designation for the treatment of pancreatic cancer.[1]
Mechanism of action
One mechanism of action is the activation of the PPAR-alpha and PPAR-gamma receptors which in turn up-regulate the expression of the TRIB3 gene, leading to inhibition of the PI3K/AKT/mTOR pathway. This pathway is excessively activated in most human cancers, supporting tumor growth. It is a principal target of various new anti-tumour drugs. Tumor cells are killed via autophagic cell death, rather than apoptosis.[3][4]
ABTL0812 activates the PPAR receptors, inducing TRIB3 over-expression. TRIB3 binds to the Akt oncogene and inhibits the Akt/mTOR axis.[3]
Clinical trials
ABTL0812 showed efficacy in Phase I clinical trials in patients with advanced cancer, with low toxicity and high tolerability.[3]
References
- “Ability Pharmaceuticals Announces Orphan Drug Designation in the US for ABTL0812 in Pancreatic Cancer”. Ability Pharmaceuticals SL.
- “Ability Pharmaceuticals Announces Positive Phase 1 1b Study Results Of ABTL0812 In Cancer Patients With Advanced Solid Tumors”. http://www.biospace.com.
- “New mechanism of antitumor action identified”. Medical Xpress. 25 January 2016.
- Erazo T, Lorente M, López-Plana A, Muñoz-Guardiola P, Fernández-Nogueira P, García-Martínez JA, et al. (May 2016). “The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase”. Clinical Cancer Research. 22 (10): 2508–19. doi:10.1158/1078-0432.ccr-15-1808. hdl:2445/207600. PMID 26671995.
| Clinical data | |
|---|---|
| Other names | α-Hydroxylinoleic acid; 2-Hydroxylinoleic acid; ABTL-0812 |
| Legal status | |
| Legal status | Investigational |
| Identifiers | |
| IUPAC name | |
| CAS Number | 57818-44-7 |
| PubChem CID | 21158511 |
| ChemSpider | 20118100 |
| UNII | 0DE74TJ7EZ |
| ChEBI | CHEBI:136927 |
| CompTox Dashboard (EPA) | DTXSID301258077 |
| Chemical and physical data | |
| Formula | C18H32O3 |
| Molar mass | 296.451 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
/////////Ibrilatazar, peroxisome proliferator activated receptor (PPAR) alpha and gamma agonist, antineoplastic, ABILITY PHARMA, ABTL 0812, alpha-Hydroxylinoleic acid, ABTL0812
Fovinaciclib
Fovinaciclib
CAS 2146171-49-3
MF C29H40N8OS
Exact Mass: 548.3046
Molecular Weight: 548.75
7-cyclopentyl-N,N-dimethyl-2-({5-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]pyridin-2-yl}amino) thieno[3,2-d]pyrimidine-6-carboxamide
7-cyclopentyl-N,N-dimethyl-2-((5-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)pyridin-2-yl)amino)thieno[3,2-d]pyrimidine-6-carboxamide
7-cyclopentyl-N, N-dimethyl-2- ( (5- (4- (4-methylpiperazin-1-yl) piperidin-1-yl) pyridin-2-yl) amino) thieno [3, 2-d] pyrimidine-6-carboxamide
7-Cyclopentyl-N,N-dimethyl-2-((5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)pyridin-2-yl)amino Thieno[3,2-d]pyrimidine-6-carboxamide
cyclin dependent kinase inhibitor, antineoplastic, Fovinaciclibum, LPW3H579X8, inzhou Aohong Pharmaceutical Co
- OriginatorChongqing Fochon Pharmaceutical
- DeveloperAhon Pharmaceutical; Chongqing Fochon Pharmaceutical; Shanghai Fosun Pharmaceutical
- Class2 ring heterocyclic compounds; Amides; Amines; Antineoplastics; Cyclopentanes; Piperazines; Piperidines; Pyridines; Pyrimidines; Small molecules; Thiophenes
- Mechanism of ActionCyclin-dependent kinase 4 inhibitors; Cyclin-dependent kinase 6 inhibitors
- MarketedHER2 negative breast cancer
- No development reportedSolid tumours
- 04 Sep 2025Chemical structure information added.
- 02 Sep 2025Launched for HER2-negative-breast-cancer (Late-stage disease, Second-line therapy or greater) in China (PO) (Shanghai Henlius Biotech pipeline, September 2025)
- 26 Aug 2025Registered for HER2-negative-breast-cancer (Late-stage disease, Second-line therapy or greater) in China (PO) prior to August 2025
Fovinaciclib is an orally bioavailable inhibitor of cyclin-dependent kinase (CDK) types 4 (CDK4) and 6 (CDK6), with potential antineoplastic activity. Upon administration, fovinaciclib selectively inhibits CDK4 and CDK6, which inhibits the phosphorylation of retinoblastoma protein (Rb) early in the G1 phase, prevents CDK-mediated G1/S transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play key roles in the regulation of both cell cycle progression from the G1-phase into the S-phase and cell proliferation.
On May 29, 2025, China’s National Medical Products Administration (NMPA) approved the Class 1 innovative drug Fovinaciclib (CDK4&6 inhibitor), developed by Jinzhou Aohong Pharmaceutical Co., Ltd. This medication, in combination with fulvestrant, is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative recurrent or metastatic breast cancer, who have experienced disease progression following prior endocrine therapy.
Notably, Fovinaciclib represents an excellent example of scaffold hopping—its design replaces the pyrrolo-pyrimidine core of Ribociclib (first approved on March 13, 2017) with a thieno-pyrimidine ring.
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=CN236278427&_cid=P21-MGRD95-18783-1
| Example 3 |
| 7-Cyclopentyl-N,N-dimethyl-2-((5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)pyridin-2-yl)amino Thieno[3,2-d]pyrimidine-6-carboxamide (3) |
According to the synthesis method of Example 2, CH
3 CHO replaced by CH
2 O, to prepare the title compound 7-cyclopentyl-N,N-dimethyl-2-((5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)pyridin-2-yl)amino)thieno[3,2-d]pyrimidine-6-carboxamide (3). MS-ESI (m/z): 549 [M+1] + .
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017193872&_cid=P21-MGRDEF-24321-1
[0266]
7-cyclopentyl-N, N-dimethyl-2- ( (5- (4- (4-methylpiperazin-1-yl) piperidin-1-yl) pyridi n-2-yl) amino) thieno [3, 2-d] pyrimidine-6-carboxamide (5)
[0267]
To a solution of 7-cyclopentyl-N, N-dimethyl-2- ( (5- (4- (piperazin-1-yl) piperidin-1-yl) pyridin-2-yl) amino) thieno [3, 2-d] pyrimidine-6-carboxamide (4) (1.5 g, 2.8 mmol) in DCM (45 mL) was added NaBH (OAc) 3(3.56 mg, 16.8 mmol) followed by CH 2O (40％in water, 252 mg, 3.4 mmol) . The mixture was stirred at r.t. for 30 min. The mixture was diluted with saturated aqueous NaHCO 3(100 mL) and extracted with DCM (2 × 30 mL) . The extracts were dried over Na 2SO 4. Solvents were evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with 96: 3: 1 DCM/methanol/ammonia to give 7-cyclopentyl-N, N-dimethyl-2- ( (5- (4- (4-methylpiperazin-1-yl) piperidin-1-yl) pyridin-2-yl) amino) thieno [3, 2-d] pyrimidine-6-carboxamide (5) . MS-ESI (m/z) : 549 [M + 1] +.
PAT
- Certain protein kinase inhibitorsPublication Number: JP-2019516790-APriority Date: 2016-05-07
- Certain protein kinase inhibitorsPublication Number: US-2019209566-A1Priority Date: 2016-05-07
- Certain protein kinase inhibitorsPublication Number: WO-2017193872-A1Priority Date: 2016-05-07
- Certain protein kinase inhibitorsPublication Number: US-10835535-B2Priority Date: 2016-05-07Grant Date: 2020-11-17
- A class of protein kinase inhibitorsPublication Number: CN-109153686-BPriority Date: 2016-05-07Grant Date: 2021-04-30
- specific protein kinase inhibitorsPublication Number: KR-102374033-B1Priority Date: 2016-05-07Grant Date: 2022-03-14
- Certain protein kinase inhibitorsPublication Number: EP-3452484-B1Priority Date: 2016-05-07Grant Date: 2023-07-05
- Certain protein kinase inhibitorsPublication Number: ES-2954148-T3Priority Date: 2016-05-07Grant Date: 2023-11-20
AS ON JUNE2025 4.45 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
……
//////////Fovinaciclib, CHINA 2025, APPROVALS 2025, cyclin dependent kinase inhibitor, antineoplastic, Fovinaciclibum, LPW3H579X8, inzhou Aohong Pharmaceutical Co
Foselutoclax
Foselutoclax
CAS 2271269-01-1
MF C53H59ClF3N6O10PS3 MW 1159.7 g/mol
(10R)-14-chloro-25-methyl-7,7-dioxo-10-[(phenylsulfanyl)methyl]-134-(phosphonooxy)-21-(propan-2-yl)-83-(trifluoromethanesulfonyl)-21H-7λ6-thia-6,9-diaza-4(1,4)-piperazina-13(1)-piperidina-2(2,3)-pyrrola-1(1),3(1,3),5,8(1,4)-tetrabenzenatridecaphane-24-carboxylic acid
5-(4-chlorophenyl)-2-methyl-4-[3-[4-[4-[[4-[[(2R)-1-phenylsulfanyl-4-(4-phosphonooxypiperidin-1-yl)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylamino]phenyl]piperazin-1-yl]phenyl]-1-propan-2-ylpyrrole-3-carboxylic acid
B-cell lymphoma 2 (Bcl-2) inhibitor, antineoplastic, VT53CL5GES, UBX 1325
Foselutoclax is an investigational new drug that is being evaluated for the treatment of age-related eye diseases, particularly diabetic macular edema (DME) and wet age-related macular degeneration (AMD). Developed by Unity Biotechnology, this senolytic compound acts as a potent inhibitor of Bcl-xL, a protein that senescent cells rely on for survival.[1] Foselutoclax is designed to selectively eliminate senescent cells in the retina, potentially addressing the underlying causes of vision loss in these conditions.[2]
- Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE)CTID: NCT06011798Phase: Phase 2Status: CompletedDate: 2025-08-05
- Safety, Tolerability and Evidence of Activity Study of UBX1325 in Patients With Diabetic Macular Edema (BEHOLD)CTID: NCT04857996Phase: Phase 2Status: CompletedDate: 2024-05-16
- Safety and Tolerability Study of UBX1325 in Patients With Diabetic Macular Edema or Neovascular Age-Related Macular DegenerationCTID: NCT04537884Phase: Phase 1Status: CompletedDate: 2022-03-10
REF
- Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial resultsPublication Name: Nature MedicinePublication Date: 2024-02PMID: 38321220DOI: 10.1038/s41591-024-02802-4
- Senolytics in the treatment of diabetic retinopathyPublication Name: Frontiers in PharmacologyPublication Date: 2022-08-26PMCID: PMC9462063PMID: 36091769DOI: 10.3389/fphar.2022.896907
- Senolytic drugs: from discovery to translationPublication Name: Journal of Internal MedicinePublication Date: 2020-08-04PMCID: PMC7405395PMID: 32686219DOI: 10.1111/joim.13141
- bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell deathPublication Name: CellPublication Date: 1993-08-27PMID: 8358789DOI: 10.1016/0092-8674(93)90508-n
PAT
Treatment of Lung Diseases Using Pharmaceutical Agents that Eliminate Senescent Cells
Publication Number: US-2020354336-A9
Priority Date: 2017-08-11
- Senescent Cells and for Treating CancerPublication Number: US-2022017485-A1Priority Date: 2018-06-13
- Acyl sulfonamides that are bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancerPublication Number: EP-4335516-A2Priority Date: 2018-06-13
- Methods of Inhibiting Pathological AngiogenesisPublication Number: US-2020253991-A1Priority Date: 2017-10-31
- Methods of inhibiting pathological angiogenesisPublication Number: US-11129838-B2Priority Date: 2017-10-31Grant Date: 2021-09-28
- Treatment of Lung Diseases Using Pharmaceutical Agents that Eliminate Senescent CellsPublication Number: US-2020199103-A1Priority Date: 2017-08-11
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US279621490&_cid=P21-MGPXU3-15237-1
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US421382898&_cid=P21-MGPXWE-19244-1
A crystalline solid meglumine salt of of (R)-5-(4-chlorophenyl)-1-isopropyl-2-methyl-4-(3-(4-(4-((4-((1-(phenylthio)-4-(4-((phosphonooxy)methyl)piperidin-1-yl)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonamido)phenyl)piperazin-1-yl)phenyl)-1H-pyrrole-3-carboxylic acid, the compound of Formula I:
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US348024244&_cid=P21-MGPXWE-19244-1
AS ON JUNE2025 4.45 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
……
| Clinical data | |
|---|---|
| Other names | UBX1325 |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2271269-01-1 |
| PubChem CID | 147562879 |
| IUPHAR/BPS | 13366 |
| ChemSpider | 115277082 |
| UNII | VT53CL5GES |
| Chemical and physical data | |
| Formula | C53H59ClF3N6O10PS3 |
| Molar mass | 1159.69 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
References
- Crago SM (22 June 2023). “Design for Phase 2B ASPIRE Study of UBX1325 for DME announced by UNITY”. Modern Retina. Archived from the original on 13 August 2024.
- Macha N, Yu M, Sapieha P, Klier S, Ghosh A, White L, et al. (September 2024). “Multifocal Electroretinography Changes after UBX1325 (Foselutoclax) Treatment in Neovascular Age-Related Macular Degeneration”. Journal of Clinical Medicine. 13 (18): 5540. doi:10.3390/jcm13185540. PMC 11433175. PMID 39337030.
//////////foselutoclax, antineoplastic, VT53CL5GES, UBX 1325
New Drug Approvals 
