Home » Articles posted by DR ANTHONY MELVIN CRASTO Ph.D (Page 6)
Author Archives: DR ANTHONY MELVIN CRASTO Ph.D
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 |
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
Lomedeucitinib
Lomedeucitinib
CAS 2328068-29-5
MF C18H172H3N6O4S
MW 419.5 g/mol
4-{[3-(methanesulfonyl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(1R)-spiro[2.2]pentane-1-carboxamido]pyridazine-3-carboxamide
4-[(3-methylsulfonyl-2-pyridinyl)amino]-6-[[(2R)-spiro[2.2]pentane-2-carbonyl]amino]-N-(trideuteriomethyl)pyridazine-3-carboxamide
Janus kinase inhibitor, anti-inflammatory, BMS-986322, BMS 986322, EYQ7KA55XA
Lomedeucitinib is an investigational new drug that is being evaluated for the treatment of psoriasis and psoriatic arthritis. It is a tyrosine kinase 2 (TYK2) inhibitor.[1]
- A Study to Evaluate Effectiveness and Safety of BMS-986322 in Participants With Moderate-to-Severe PsoriasisCTID: NCT05730725Phase: Phase 2Status: CompletedDate: 2024-09-19
- A Study to Evaluate the Drug Levels, Metabolism, and Removal of BMS-986322 in Healthy Adult Male ParticipantsCTID: NCT06088264Phase: Phase 1Status: CompletedDate: 2024-03-29
- A Study Investigating Interactions Between BMS-986322 and Rosuvastatin, Metformin and Methotrexate in Healthy ParticipantsCTID: NCT05615012Phase: Phase 1Status: CompletedDate: 2024-03-27
- A Study to Investigate the Interaction of BMS-986322 and a Combined Oral Hormonal Contraceptive (Ethinyl Estradiol [EE]/Norethindrone [NET]) in Healthy Female ParticipantsCTID: NCT05579574Phase: Phase 1Status: CompletedDate: 2023-08-18
- A Study to Assess the Safety and Tolerability of BMS-986322 in Healthy Participants of Japanese DescentCTID: NCT05546151Phase: Phase 1Status: CompletedDate: 2023-06-22
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US333829535&_cid=P10-MHIXWK-98212-1
General Scheme for Examples 252 and 253:
Example 252
Step 1
| A mixture of cesium carbonate (149 mg, 0.457 mmol), Xantphos (14.43 mg, 0.025 mmol), Pd 2(dba) 3 (11.42 mg, 0.012 mmol), 6-chloro-N-(methyl-d3)-4-((3-(methylthio)pyridin-2-yl)amino)pyridazine-3-carboxamide (65 mg, 0.208 mmol), and (R)-spiro[2.2]pentane-1-carboxamide (50.8 mg, 0.457 mmol) in dioxane (3 mL) was degassed using a vacuum/N2 fill cycle three times. The reaction was heated at 110° C. for 16 hours. The reaction was diluted with water and DCM. The DCM layer was separated and washed two more times with water and then dried (Na 2SO 4), filtered and concentrated. Purification via automated flash chromatography, eluting with methanol in DCM from 0 to 10%, gave the title compound (R)—N-(methyl-d3)-4-((3-(methylthio)pyridin-2-yl)amino)-6-(spiro[2.2]pentane-1-carboxamido)pyridazine-3-carboxamide (54 mg, 67% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 12.15 (br s, 1H), 9.88 (s, 1H), 8.68 (br s, 1H), 8.36 (br d, J=3.5 Hz, 1H), 8.25 (br s, 1H), 7.72 (br d, J=7.4 Hz, 1H), 6.97 (br dd, J=7.0, 5.1 Hz, 1H), 2.51 (s, 3H), 2.21-2.09 (m, 1H), 1.58-1.10 (m, 6H), 1.08-0.93 (m, 5H). |
| LCMS (ESI) m/e 388.1 [(M+H) +, calc’d C 18H 18D 3N 6O 2S 1, 388.1]; LC/MS retention time (method D): t R=0.80 min. |
Step 2
To a suspension of hydrogen peroxide (30% solution in water, 0.258 mL, 2.52 mmol) and (R)—N-(methyl-d3)-4-((3-(methylthio)pyridin-2-yl)amino)-6-(spiro[2.2]pentane-1-carboxamido)pyridazine-3-carboxamide (0.0489 g, 0.126 mmol) in AcOH (1 mL) was added sodium tungstate dihydrate (0.042 g, 0.126 mmol) at room temperature. After stirring at room temperature for 1 hour, the reaction was diluted with water, basified with Na 2CO 3 powder and extracted three times with DCM. The DCM layers were combined, washed with Na 2S 2O 3 (5% solution), dried (Na 2SO 4), filtered and concentrated. The crude product was purified using reverse phase prepHPLC to give the title compound (R)—N-(methyl-d3)-4-((3-(methylsulfonyl)pyridin-2-yl)amino)-6-(spiro[2.2]pentane-1-carboxamido)pyridazine-3-carboxamide (16.2 mg, 31%) as a colorless solid. 1H NMR (500 MHz, DMSO-d 6) δ 12.07 (s, 1H), 11.22 (s, 1H), 9.49 (s, 1H), 9.16 (s, 1H), 8.63 (dd, J=4.6, 1.5 Hz, 1H), 8.29 (dd, 0.1=7.8, 1.4 Hz, 1H), 7.34 (dd, 0.1=7.8, 4.7 Hz, 1H), 2.48-2.43 (m, 1H), 1.46-1.41 (m, 1H), 1.42-1.36 (m, 1H), 0.95-0.82 (m, 3H), 0.80-0.73 (m, 1H). (3H methyl sulfone was buried under DMSO peak). LCMS (ESI) m/e 420.0 [(M+H) +, calc’d C 18H 18D 3N 6O 4S, 420.1]; LC/MS retention time (method E): t R=1.38 min; OR: −205.39 (20° C.).
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US242383764&_cid=P10-MHIXVD-97150-1
PAT
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: US-11787779-B2Priority Date: 2017-11-21Grant Date: 2023-10-17
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: US-2024002364-A1Priority Date: 2017-11-21
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: KR-102702228-B1Priority Date: 2017-11-21Grant Date: 2024-09-02
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: NZ-805343-APriority Date: 2017-11-21
- Sulfonepyridine alkylamide-substituted heteroaryl compoundsPublication Number: JP-2023098942-APriority Date: 2017-11-21
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: AU-2023255024-A1Priority Date: 2017-11-21
- Heteroaryl compounds substituted with sulfone pyridinylalkylamidesPublication Number: CN-111315737-BPriority Date: 2017-11-21Grant Date: 2024-06-18
- The heteroaryl compounds are substituted with sulfone-pyridine alkyl amidesPublication Number: IL-274816-B2Priority Date: 2017-11-21
- Sulfonepyridine alkylamide substituted heteroaryl compoundsPublication Number: JP-7490107-B2Priority Date: 2017-11-21Grant Date: 2024-05-24
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: AU-2022228101-A1Priority Date: 2017-11-21
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: TW-I776994-BPriority Date: 2017-11-21Grant Date: 2022-09-11
- Sulfonepyridine alkylamide-substituted heteroaryl compoundsPublication Number: JP-7258903-B2Priority Date: 2017-11-21Grant Date: 2023-04-17
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: AU-2022228101-B2Priority Date: 2017-11-21Grant Date: 2023-08-03
- The heteroaryl compounds are substituted with sulfone-pyridine alkyl amidesPublication Number: IL-274816-B1Priority Date: 2017-11-21
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: US-2019152948-A1Priority Date: 2017-11-21
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: CA-3083122-A1Priority Date: 2017-11-21
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: KR-20200089706-APriority Date: 2017-11-21
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: US-11021462-B2Priority Date: 2017-11-21Grant Date: 2021-06-01
- Sulfone pyridine alkyl amide-substituted heteroaryl compoundsPublication Number: US-2021253554-A1Priority Date: 2017-11-21
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 | BMS-986322 |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2328068-29-5 |
| PubChem CID | 138620496 |
| IUPHAR/BPS | 13210 |
| UNII | EYQ7KA55XA |
| KEGG | D12725 |
| ChEMBL | ChEMBL5314608 |
| Chemical and physical data | |
| Formula | C18H17D3N6O4S |
| Molar mass | 419.47 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
References
- Ahsan S, Degener R, Schlamp M (2024). “Non-Invasive Treatments Invade the Psoriasis Pipeline”. Drugs in Context. 13: 2024–5–6. doi:10.7573/dic.2024-5-6. PMC 11313207. PMID 39131603.
////////lomedeucitinib, Janus kinase inhibitor, anti-inflammatory, BMS-986322, BMS 986322, EYQ7KA55XA
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
Linustedastat
Linustedastat
CAS 2254299-48-2
MFC26H29F2N3O2 MW 453.5 g/mol
FOR-6219, OG-6219, FOR 6219, OG 6219, PP3PLL7GZY, Phase 2, Endometriosis
3-[(8R,9S,13S,14S,15R,17E)-4-fluoro-17-hydroxyimino-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-15-yl]-N-(5-fluoro-2-pyridinyl)propanamide
- (15beta,17E)-4-Fluoro-N-(5-fluoro-2-pyridinyl)-17-(hydroxyimino)estra-1,3,5(10)-triene-15-propanamide
- 3-[(17E)-4-fluoro-17-(hydroxyimino)estra-1,3,5(10)-trien-15beta-yl]-N-(5-fluoropyridin-2-yl)propanamide
- Estra-1,3,5(10)-triene-15-propanamide, 4-fluoro-N-(5-fluoro-2-pyridinyl)-17-(hydroxyimino)-, (15beta,17E)-
3-[(17E)-4-fluoro-17-(hidroxiimino)estra-1,3,5(10)-trien-15β-il]-N-(5-fluoropiridin-2-il)propanamida
inhibidor de la hidroxiesteroide 17-beta deshidrogenasa 1(HSD17B1)
- OriginatorHormos Medical; Solvay Pharmaceuticals B.V.; University of Turku
- DeveloperOrganon
- ClassSmall molecules
- Mechanism of ActionEstradiol dehydrogenase inhibitors
- Phase IIEndometriosis
- 02 Jul 2025Efficacy data from the phase II ELENA trial in Endometriosis released by Organon
- 28 May 2025Organon completes a phase-II clinical trials in Endometriosis (In adults) in Latvia, Sweden, Poland, Italy, France, Hungary, Germany, Czech Republic, Czech Republic, Bulgaria, Belgium, USA (PO) (NCT05560646)
- 28 Nov 2023No recent reports of development identified for phase-I development in Endometriosis(In volunteers) in United Kingdom (PO)
Linustedastat (developmental code names FOR-6219 and OG-6219) is a 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1; HSD17B1) inhibitor which is under development for the treatment of endometriosis.[1][2][3][4][5] It is a steroidal compound derived from estrone and works by preventing the formation of the more potent estrogen estradiol from the minimally active precursor estrone.[1][2][5] This in turn results in antiestrogenic effects that may be useful in the treatment of estrogen-dependent conditions.[1][2][5] As of November 2023, the drug is in phase 2 clinical trials for endometriosis.[1][2] It is also under preclinical investigation for treatment of breast cancer and endometrial cancer.[5]
A Study to Investigate Efficacy and Safety of OG-6219 BID in 3 Dose Levels Compared With Placebo in Participants Aged 18 to 49 With Moderate to Severe Endometriosis-related Pain
CTID: NCT05560646
Phase: Phase 2
Status: Completed
Date: 2025-05-29
Pat
WO2018224736
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018224736&_cid=P21-MHFVBM-49409-1
Compound 26
3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide
Example 26 was prepared in 94% yield from the compound 25 by the same method as with Example 2 in three hours reaction time.
1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.12 – 2.48 (m, 15 H), 2.57 – 2.78 (m, 1 H), 2.80 – 2.95 (m, 2 H), 6.79 – 7.01 (m, 2 H), 7.18 – 7.38 (m, 1 H), 7.72 (td, 1 H), 8.15 (dd, 1 H), 8.31 (d, 1 H), 10.18 (s, 1 H), 10.64 (s, 1 H). MS m/z (TOF ES+): 454 (M+1).
SYNTHESIS
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 | FOR-6219; OG-6219; 3-[(17E)-4-Fluoro-17-(hydroxyimino)estra-1,3,5(10)-trien-15β-yl]-N-(5-fluoropyridin-2-yl)propanamide |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2254299-48-2 |
| PubChem CID | 171390018 |
| UNII | PP3PLL7GZY |
| KEGG | D13078 |
| Chemical and physical data | |
| Formula | C26H29F2N3O2 |
| Molar mass | 453.534 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
References
- “FOR 6219”. AdisInsight. 28 November 2023. Retrieved 15 August 2024.
- “Delving into the Latest Updates on Linustedastat with Synapse”. Synapse. 3 August 2024. Retrieved 15 August 2024.
- Barra F, Romano A, Grandi G, Facchinetti F, Ferrero S (June 2019). “Future directions in endometriosis treatment: discovery and development of novel inhibitors of estrogen biosynthesis”. Expert Opin Investig Drugs. 28 (6): 501–504. doi:10.1080/13543784.2019.1618269. hdl:11380/1201688. PMID 31072144.
- Perrone U, Evangelisti G, Laganà AS, Bogliolo S, Ceccaroni M, Izzotti A, Gustavino C, Ferrero S, Barra F (December 2023). “A review of phase II and III drugs for the treatment and management of endometriosis”. Expert Opin Emerg Drugs. 28 (4): 333–351. doi:10.1080/14728214.2023.2296080. PMID 38099328.
- Rižner TL, Romano A (2023). “Targeting the formation of estrogens for treatment of hormone dependent diseases-current status”. Front Pharmacol. 14 1155558. doi:10.3389/fphar.2023.1155558. PMC 10175629. PMID 37188267.
Several compounds with inhibitory action on the enzyme HSD17B1 have been developed and one steroidal compound, a competitive HSD17B1 inhibitor (OG-6219) recently entered the clinical phase for endometriosis […] and it is in the preclinical phase for endometrial and breast cancer (Husen et al., 2006a; Husen et al., 2006b; Konings et al., 2018b; Jarvensivu et al., 2018; Xanthoulea et al., 2021). […] Only the C15 estrone derivative developed by Organon Finland, former Forendo pharma (compound FOR-6219/OR-6219) reached the clinical phase for endometriosis with three clinical trials registered in the database Clinical Trails (Table 2). Phase 1 and 1b trials NCT04686669 and NCT03709420 determined the bio-availability of the compound administered orally as gelatine capsule in 12 subjects (NCT04686669) and then the safety, tolerability, food interactions, the pharmacokinetics and pharmacodynamics of escalating doses of the drug in 87 subjects (NCT03709420). The phase 2 randomized, double-blind, Elena study (NCT05560646) is currently recruiting patients and aims at evaluating the efficacy and safety of OG-6219 in women with moderate to severe endometriosis […]
External links
//////////Linustedastat, FOR-6219, OG-6219, FOR 6219, OG 6219, PP3PLL7GZY, Phase 2, Endometriosis
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
Imocitrelvir
Imocitrelvir
CAS 343565-99-1
MFC26H29N5O7 MW523.5 g/mol
ethyl (2E,4S)-4-{(2S)-2-[3-(5-methyl-1,2-oxazole-3-carboxamido)-2-oxopyridin-1(2H)-yl]pent-4-ynamido}-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate
ethyl (E,4S)-4-[[(2S)-2-[3-[(5-methyl-1,2-oxazole-3-carbonyl)amino]-2-oxo-1-pyridinyl]pent-4-ynoyl]amino]-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate
protease inhibitor, antiviral, AG-7404, V-7404, AG 7404, V 7404, VQ1AN3OO42
Imocitrelvir is an investigational new drug that is being evaluated for the treatment of viral infections. It is a 3C protease inhibitor in picornaviruses. Originally developed by Pfizer for treating human rhinovirus infections,[1] this small molecule has shown promise against a broader range of viruses, including polioviruses.[2][3]
SYN
Publication Name: Journal of Medicinal Chemistry
Publication Date: 2003-09-17
PMID: 14521419
DOI: 10.1021/jm030166l
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2016044656&_cid=P21-MHBDH2-20719-1
PAT
PAT
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2001040189&_cid=P21-MHBDI9-21481-1
EXAMPLE 21
Preparation of Compound 22: tra«5-(4S,3″”S)-4-(2′-{3″-[(5′”-Methylisoxazole-3′”-carbonyl)amino]-2″-oxo-2″H-pyridin- 1 “-yl} acetylamino)-5-(2″”-oxopyrrilidin-3″”-yl)pent-2-enoic Acid Ethyl Ester
Preparation of Intermediate {3-[(5′-Methylisoxazole-3′-carbonyl)amino]-2-oxo-2H-pyridin-l-yl} acetic Acid tert-Butyl Ester
To a solution of 5-methylisoxazole-3-carboxylic acid (2′-hydroxy-4′-methylpyridin-3′-yl)amide (F2, Example 19) (0.520 g, 2.37 mmol, 1 equiv) in TΗF (20 mL) at 0 °C was added NaΗ (0.095 g, 2.37 mmol, 1.0 equiv). The resulting mixture was stirred at 0 °C for 20 min, and then t-butyl bromoacetate (0.385 mL, 2.61 mmol, 1.1 equiv) was added. The reaction mixture was stirred and warmed to room temperature for 30 min, then was partitioned between 0.5 N ΗC1 (100 mL) and EtOAc (2 x 100 mL). The combined organic layers were dried over Na2SO and were concentrated. Purification of the residue by flash column chromatography (30% EtOAc in hexanes) provided the title intermediate (0.628 g, 79%) as a white solid: IR (cm-1) 3343, 1743, 1651, 1581, 1156; Η NMR (CDC13) δ 1.52 (s, 9H), 2.53 (s, 3H), 4.65 (s, 2H), 6.32 (t, 1H, 7= 7.2), 6.51 (s, IH), 7.01 (dd, 1H, 7= 6.9, 1.8), 8.50 (dd, 1H, 7= 7.5, 1.8), 9.63 (s, br. IH); Anal. C16H19N3O5: C, H, N.
Preparation of Compound 22
The preceding intermediate was transformed into Compound 22 by a process that was analogous to that described in Example 25 for the transformation of V3 to product R3: mp = 102-106 °C; IR (cm”1) 3336, 1684, 1534, 1457; JH NMR (CDCI3) δ 1.27 (t, 3H, 7= 7.2), 1.67-1.75 (m, IH), 1.98-2.09 (m, IH), 2.37-2.49 (m, IH), 2.53 (s, 3H), 2.55-2.61 (m, IH), 3.34-3.46 (m, 2H), 3.51-3.52 (m, IH), 4.17 (q, 2H, 7= 7.2), 4.61-4.78 (m, 3H), 5.98 (dd, IH, 7 = 15.6, 1.5), 6.20 (s, br. IH), 6.35 (t, 1H, 7= 7.8), 6.51 (s, IH), 6.85 (dd, IH, 7= 15.6, 5.1), 7.17 (d, IH, 7= 7.2), 8.33 (d, IH, 7= 7.2), 8.49 (d, IH, 7= 7.5), 9.57 (s, br. IH); Anal.
C23H27N5O7: C, H, N.
EXAMPLE 24
Preparation of Compound 25: trans-(2’S,3″”‘S,4S)-4-(3,-(4″-Fluorophenyl)-2′-{3″‘-[(5″”-methylisoxazole-3″”-carbonyl)amino]-2′”-oxo-2′”H-pyridin- “-yl}propionylamino)-5-(2″ oxopyrrolidin-3′””-yl)pent-2-enoic Acid Ethyl Ester
The title compound was prepared from F2 (Example 19) in a manner analogous to that described for the conversion of U2 to 13 in Example 23 utilizing intermediate Y2 (Example 25) where appropriate: IR (cm-1) 3331, 1690, 1590, 1531, 1455; !H NMR (CDCI3) δ 1.30 (t, 3H, 7= 7.0), 1.45-1.55 (m, IH), 1.64-1.75 (m, IH), 2.03-2.31 (m, 3H), 2.49 (s, 3H), 3.10 (dd, IH, 7= 13.7, 7.9), 3.20-3.46 (m, 3H), 4.20 (q, 2H, 7= 7.0), 4.36-4.47 (m, IH), 5.67 (dd, IH, 7 = 15.7, 1.4), 5.85-5.92 (m, IH), 6.29 (t, 1H, 7= 7.2), 6.45 (s, IH), 6.70 (dd, IH, 7= 15.7, 5.7), 6.86 (s, IH), 6.90-6.97 (m, 2H), 7.10-7.16 (m, 2H), 7.60 (dd, IH, 7= 7.2, 1.6), 8.37 (dd, IH, 7 = 7.2, 1.6), 8.51 (d, IH, 7= 6.6), 9.47 (s, IH).
EXAMPLE 25
Preparation of Compound 26: tr_.«5-(2’S,3″”S,4S)-4-(2′-{3″-[(5″‘-Methyl-isoxazole-3′”-carbonyl)amino]-2″-oxo-2″H-pyridin-l”-yl}butyrylamino)-5-(2″”-oxopyrrolidin-3″”-yl)pent-2-enoic Acid Ethyl Ester (R3)
Preparation of Intermediate (2R)-2-Trifluoromethanesulfonyl-oxybutyric acid tert-butyl ester (U3)
Commercially available T3 (0.575 g, 3.59 mmol, 1 equiv) was dissolved in CH2CI2 (25 mL) and cooled in an ice bath. 2,6-Lutidine (0.836 mL, 7.18 mmol, 2 equiv) and trifluoromethanesulfonic anhydride (1.15 mL, 6.84 mmol, 1.9 equiv) were added and the reaction mixture was stirred 30 min. It was then diluted with MTBE (400 mL), washed with a mixture of brine and 1 N HCl (2:1, 100 mL) and brine (100 mL), dried over Na2SO4 and evaporated to provide the title intermediate which was used without further purification.
Preparation of Intermediate (2S)-2- {3′-[(5″-Methylisoxazole-3″-carbonyl)amino]-2′-oxo-2’H-pyri din- l’-yl} butyric Acid tert-Butyl Ester (V3)
Intermediate F2 from above (0.200 g, 0.912 mmol, 1.1 equiv) was suspended in TΗF (6 mL). Sodium hydride (60% dispersion in mineral oil, 0.0332 g, 0.830 mmol, 1 equiv) was added in one portion. After stirring 30 min, a solution of intermediate U3 (0.830 mmol, 1 equiv, based on T3) in TΗF (7 mL) was added dropwise. The resulting mixture was stirred 2 hours, then diluted with EtOAc (200 mL) and washed with brine (2 x 50 mL). The organic phase was dried over MgSO4 and evaporated. The residue was purified by flash column chromatography (25% EtOAc in hexanes) to provide the title intermediate (0.178 g, 59%) as an oil: R/= 0.30 (25% EtOAc in hexanes); IR (cm”1) 3331, 1731, 1690, 1649, 1602, 1531 ; *Η NMR (CDCI3) δ 0.93 (t, 3H, 7= 7.3), 1.45 (s, 9H), 1.83-2.01 (m, IH), 2.17-2.31 (m, IH), 2.50 (s, 3H), 5.44-5.51 (m, IH), 6.32 (t, IH, 7= 7.2), 6.48 (s, IH), 7.10 (dd, IH, 7= 7.2, 1.8), 8.45 (dd, 1H, 7= 7.2, 1.8), 9.64 (s, IH); Anal. C18H23N3O5: C, H, N.
Preparation of Intermediate (2S)-2- {3′-[(5″-Methylisoxazole-3″-carbonyl)amino]-2′-oxo-2’H-pyridin-l’-yl}butyric Acid (W3)
Intermediate V3 from above (0.143 g, 0.397 mmol, 1 equiv) was stirred for 1 h in a solution of TFA (2 mL) in CΗ2CI2 (3 mL). The volatiles were evaporated. The residue was suspended in toluene (10 mL) and concentrated to dryness, providing the title intermediate which was used without further purification.
Preparation of Intermediate trα«5-(3’S,4S)-4-Amino-5-(2′-oxopyrrolidin-3′-yl)pent-2-enoic Acid Ethyl Ester (Y2)
Intermediate X2, prepared according to the method disclosed in the co-pending application, U.S. Provisional Patent Application No. 60/150,358, filed August 24, 1999(0.130 g, 0.398 mmol, 1 equiv), was stirred for 30 min in a solution of TFA (2 mL) in CH2CI2 (3 mL). The volatiles were evaporated. The residue was suspended in toluene (10 mL) and concentrated to dryness, providing the title intermediate which was used without further purification.
Preparation of Product R3 (Compound 26)
Intermediates W3 and Y2 (as prepared above) were combined in CH2CI2 (7 mL) and cooled in an ice bath. HOBt (0.064 g, 0.47 mmol, 1.2 equiv), iP^NEt (0.484 mL, 2.78 mmol, 7 equiv) and EDC (0.084 g, 0.44 mmol, 1.1 equiv) were added sequentially. The reaction mixture was allowed to warm to 23 °C overnight, then diluted with EtOAc (500 mL) and washed with 5% KHSO4 , half saturated NaHCO3, and brine (100 mL each). The organic phase was dried over MgSO4 and evaporated. The residue was purified by flash column chromatography (gradient elution, 2→3% CH3OH in CH2CI2) to provide the title intermediate (0.119 g, 58%) as a white foam: IR (cm”1) 3331, 1684, 1649, 1590, 1531; JH NMR (CDCI3) δ 0.92 (t, 3H, J = 7.3), 1.29 (t, 3H, J = 7.1), 1.47-1.58 (m, IH), 1.62-1.77 (m, IH), 1.85-2.00 (m, IH), 2.08-2.33 (m, 4H), 2.49 (s, 3H), 3.25-3.42 (m, 2H), 4.19 (q, 2H, J = 7.1), 4.39-4.50 (m, IH), 5.73 (dd, IH, J = 8.8, 6.8), 5.97 (dd, IH, J = 15.7, 1.4), 6.34 (t, IH, J = 7.2), 6.46 (s, IH), 6.86 (dd, IH, J = 15.7, 5.9), 7.18 (s, IH), 7.59 (dd, IH, J = 7.2, 1.8), 8.42 (dd, IH, J = 7.2, 1.8), 8.58-8.62 (m, IH), 9.56 (s, 1); Anal. C25H31N5O7O.5OH2O: C, H, N.
PAT
- Treatment of infection by human enterovirus d68Publication Number: US-2020016243-A1Priority Date: 2014-09-17
- Treatment of infection by human enterovirus d68Publication Number: WO-2016044656-A1Priority Date: 2014-09-17
- Treatment of infection by human enterovirus d68Publication Number: US-2021052708-A1Priority Date: 2014-09-17
- Treatment of infection by human enterovirus D68Publication Number: US-11191817-B2Priority Date: 2014-09-17Grant Date: 2021-12-07
- Therapeutic compounds and methodsPublication Number: US-2025051283-A1
- Protease Inhibitors for Treatment or Prevention of Coronavirus DiseasePublication Number: US-2023192660-A1Priority Date: 2020-05-08
- Composition and combined medication method for treating enterovirus infectionPublication Number: US-2019030027-A1Priority Date: 2016-01-29
- Composition and combined medication method for treating enterovirus infectionPublication Number: US-10864210-B2Priority Date: 2016-01-29Grant Date: 2020-12-15
- Treatment of infection by human enterovirus D68Publication Number: US-10328128-B2Priority Date: 2014-09-17Grant Date: 2019-06-25
- Treatment of infection by human enterovirus d68Publication Number: US-2017290893-A1Priority Date: 2014-09-17
- Nucleotide and nucleoside therapeutic compositions, combinations and related uses thereofPublication Number: CN-117881402-APriority Date: 2021-05-05
- Nucleotide and nucleoside therapeutic compositions, combinations and uses related theretoPublication Number: EP-4333859-A1Priority Date: 2021-05-05
- Nucleotide and nucleoside therapeutic compositions, combinations, and related usesPublication Number: JP-2024517807-APriority Date: 2021-05-05
- Nucleotide and nucleoside therapeutic compositions, combinations and uses related theretoPublication Number: WO-2022235874-A1Priority Date: 2021-05-05
- Protease inhibitors for treatment or prevention of coronavirus diseasePublication Number: EP-4146267-A1Priority Date: 2020-05-08
- 4′-substituted nucleosides and nucleotides as antiviral agentsPublication Number: WO-2024227159-A2Priority Date: 2023-04-28
- Therapeutic compoundsPublication Number: WO-2024206284-A2Priority Date: 2023-03-27
- Antibody molecules binding to sars-cov-2Publication Number: WO-2024168061-A2Priority Date: 2023-02-07
- Predictive model for variants associated with drug resistance and theranostic applications thereofPublication Number: WO-2023172635-A1Priority Date: 2022-03-08
- Nucleotide and nucleoside therapeutic compositions, combinations and uses related theretoPublication Number: CA-3216679-A1Priority Date: 2021-05-05
LIT
- Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404Publication Name: Antiviral ResearchPublication Date: 2022-12PMCID: PMC9632241PMID: 36336176DOI: 10.1016/j.antiviral.2022.105458
- Bioisosteres of the Phenyl Ring: Recent Strategic Applications in Lead Optimization and Drug DesignPublication Name: Journal of Medicinal ChemistryPublication Date: 2021-09-30PMID: 34591488DOI: 10.1021/acs.jmedchem.1c01215
- In Vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus InhibitorsPublication Name: Journal of Medicinal ChemistryPublication Date: 2018-12-04PMCID: PMC9169555PMID: 30512950DOI: 10.1021/acs.jmedchem.8b01482
- A Novel Series of Highly Potent Small Molecule Inhibitors of Rhinovirus ReplicationPublication Name: Journal of Medicinal ChemistryPublication Date: 2017-06-15PMID: 28581749DOI: 10.1021/acs.jmedchem.7b00175
- Anti-poliovirus activity of protease inhibitor AG-7404, and assessment of in vitro activity in combination with antiviral capsid inhibitor compoundsPublication Name: Antiviral ResearchPublication Date: 2013-05PMID: 23499651DOI: 10.1016/j.antiviral.2013.03.003
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 | AG-7404, V-7404 |
| Identifiers | |
| IUPAC name | |
| CAS Number | 343565-99-1 |
| PubChem CID | 5280053 |
| IUPHAR/BPS | 13223 |
| UNII | VQ1AN3OO42 |
| ChEMBL | ChEMBL141157 |
| Chemical and physical data | |
| Formula | C26H29N5O7 |
| Molar mass | 523.546 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
References
- “Imocitrelvir”. PatSnap.
- Xie H, Rhoden EE, Liu HM, Ogunsemowo F, Mainou BA, Burke RM, et al. (November 2024). “Antiviral Development for the Polio Endgame: Current Progress and Future Directions”. Pathogens. 13 (11). Basel, Switzerland: 969. doi:10.3390/pathogens13110969. PMC 11597170. PMID 39599522.
- Bandyopadhyay AS, Burke RM, Hawes KM (June 2024). “Polio Eradication: Status, Struggles and Strategies”. The Pediatric Infectious Disease Journal. 43 (6): e207-211. doi:10.1097/INF.0000000000004330. PMID 38564755.
////////Imocitrelvir, protease inhibitor, antiviral, AG-7404, V-7404, AG 7404, V 7404, VQ1AN3OO42
Ilantimod
Ilantimod
CAS 2242464-44-2
MF C18H18ClN5O3 MW 387.82
6-(4-chlorophenyl)-N-[(2S)-1-hydroxypropan-2-yl]-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide
(S)-6-(4-chlorophenyl)-N-(1-hydroxypropan-2-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide
immunomodulator, BAY-2416964, BAY 2416964, Y87V4WXQ4Z
Ilantimod is an orally available formulation containing a small molecule antagonist of the aryl hydrocarbon receptor (AhR; class E basic helix-loop-helix protein 76; bHLHe76) with potential immunomodulating and antineoplastic activities. Upon oral administration, ilantimod specifically binds to AhR, inhibits AhR activation, and prevents AhR-mediated signaling. Abrogation of AhR activation prevents the activation of immune-tolerant dendritic cells (DCs) and regulatory T-cells (Tregs) in the tumor microenvironment (TME). This may restore the immune response against tumor cells. AhR, a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors, has important roles in regulating immunity and cellular differentiation. AhR can exhibit both pro-oncogenic and tumor suppressor-like functions depending on the tumor type; therefore, its expression may serve as a negative or positive prognostic factor.
- A Study to Learn How Safe the Study Drug BAY 2416964 (AhR Inhibitor) in Combination With the Treatment Pembrolizumab is, How This Combination Affects the Body, the Maximum Amount That Can be Given, How it Moves Into, Through and Out of the Body and Its Action Against Advanced Solid Cancers in AdultsCTID: NCT04999202Phase: Phase 1Status: TerminatedDate: 2025-02-10
- A First-in-Humans Dose Finding Study for an Aryl Hydrocarbon Receptor Inhibitor (AhRi) in Patients With Advanced CancerCTID: NCT04069026Phase: Phase 1Status: CompletedDate: 2024-03-06
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018146010&_cid=P11-MHAFJG-41587-1
Example 17
6-(4-Chlorophenyl)-/V-[(2S)-1 -hydroxypropan-2-yl]-2-(1 -methyl-1 H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide
A solution of 80 mg intermediate 1 1 , 29.1 mg (2S)-2-aminopropan-1 -ol, 1 10 mg HATU and 0.1 mL ethyldiisopropylamine in 5 mL of DMF was stirred at room temperature for 14 hours. Then the reaction was quenched by water, and the mixture was extracted with dichloromethane two times. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The residue was subjected to RP-HPLC ((column: X-Bridge C18 5μηι 100x30mm, mobile phase: acetonitrile / water (0.1 vol% formic acid)-gradient)) to yield 50 mg 6-(4-chlorophenyl)-/V-[(2S)-1 -hydroxypropan-2-yl]-2-(1 -methyl-1 H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide
1H-NMR (400 MHz, CDC ): δ [ppm] = 1.34 (d, 3H); 2.73-2.82 (m, 1 H); 3.66-3.73 (m, 1 H); 3.77-3.84 (m, 1 H); 3.98 (s, 3H); 4.26-4.36 (m, 1 H); 7.49 (d, 2H); 7.87 (d, 2H); 8.12 (s, 1 H); 8.33 (s, 1 H); 8.69 (s, 1 H); 9.82 (bd, 1 H).
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=US438191125&_cid=P11-MHAFQQ-47913-1
SEE EX 17
PAT
- 2-Heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamide for the treatment of cancerPublication Number: KR-102627266-B1Priority Date: 2017-02-09Grant Date: 2024-01-24
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: US-11795164-B2Priority Date: 2017-02-09Grant Date: 2023-10-24
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: US-2024294505-A1Priority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamidesPublication Number: TW-I770113-BPriority Date: 2017-02-09Grant Date: 2022-07-11
- 2-Heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: CN-110678459-BPriority Date: 2017-02-09Grant Date: 2023-04-04
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: US-2023121195-A1Priority Date: 2017-02-09
- 2-Heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: CN-116531380-APriority Date: 2017-02-09
- 2-Heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: CN-116554152-APriority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: WO-2018146010-A1Priority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: EP-3580211-B1Priority Date: 2017-02-09Grant Date: 2020-12-02
- 2-HETEROARYL-3-OXO-2,3-DIHYDROPYRIDAZINE-4-CARBOXAMIDES FOR THE TREATMENT OF CANCERPublication Number: HR-P20210143-T1Priority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: AU-2018217860-B2Priority Date: 2017-02-09Grant Date: 2021-07-08
- 2-Troaril-3-oxo-3,2-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: IL-268469-APriority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: CA-3052718-A1Priority Date: 2017-02-09
- 2-Heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamide for the treatment of cancerPublication Number: CN-110678459-APriority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: EP-3580211-A1Priority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamide for the treatment of cancerPublication Number: KR-20190115460-APriority Date: 2017-02-09
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamidePublication Number: TW-201840549-APriority Date: 2017-02-09
- Combination of an ahr-inhibitor and an pd1-inhibitor antibody and its use in the treatment of cancerPublication Number: EP-4076462-A1Priority Date: 2019-12-16
- Combinations of AHR inhibitors and PD1 inhibitor antibodies and their use in the treatment of cancerPublication Number: JP-2023505907-APriority Date: 2019-12-16
- Combinations of AHR-inhibitors and PD1-inhibitor antibodies and their use in the treatment of cancerPublication Number: KR-20220128622-APriority Date: 2019-12-16
- Combination of an ahr-inhibitor and an pd1-inhibitor antibody and its use in the treatment of cancerPublication Number: US-2023084899-A1Priority Date: 2019-12-16
- 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancerPublication Number: AU-2018217860-A1Priority Date: 2017-02-09
- Methods and compositions for treating inflammatory and fibrotic pulmonary disordersPublication Number: US-2021401987-A1Priority Date: 2020-03-20
- Methods and compositions for treating inflammatory and fibrotic pulmonary disordersPublication Number: EP-4121111-A1Priority Date: 2020-03-20
- Combination of an ahr-inhibitor and an pd1-inhibitor antibody and its use in the treatment of cancerPublication Number: WO-2021122434-A1Priority Date: 2019-12-16
- Combination of an AhR-inhibitor and an PD1-inhibitor antibody and its use in the treatment of cancerPublication Number: AU-2020403801-A1Priority Date: 2019-12-16
- Combinations of AHR inhibitor and PD1 inhibitor antibodies and their use in cancer therapyPublication Number: CN-114786674-APriority Date: 2019-12-16
- Compositions and methods for treating myelin deficiency by rejuvenating glial progenitor cellsPublication Number: US-2023190961-A1Priority Date: 2021-10-20
- Prophylactic or therapeutic agent for severe pulmonary hypertension, refractory pulmonary hypertension, or drug-induced pulmonary hypertensionPublication Number: WO-2022149605-A1Priority Date: 2021-01-08
- Deuterated 2-arylheterocycle-3-oxo-2,3-dihydropyridazine-4-carboxamide inhibitor and preparation method therefor and application thereofPublication Number: EP-4253374-A1Priority Date: 2020-11-27
- Heteroaromatic ahr inhibitorPublication Number: WO-2022078356-A1Priority Date: 2020-10-15
- Methods and compositions for treating inflammatory and fibrotic pulmonary disordersPublication Number: WO-2021188849-A1Priority Date: 2020-03-20
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
……
///////////Ilantimod, immunomodulator, BAY-2416964, BAY 2416964, Y87V4WXQ4Z
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
New Drug Approvals 
