Lurbinectedin

New Drug Approvals

Lurbinectedin

(1’R,6R,6aR,7R,13S,14S,16R)-5-(Acetyloxy)-2′,3′,4′,6,6a,7,9′-decahydro-8,14-dihydroxy-6′,9-dimethoxy-4,10,23-trimethyl-spiro(6,16-(epithiopropaneoxymethano)-7.13-imino-12H-1,3-dioxolo[7,8]soquino[3,2-b][3]benzazocine-20,1′-[1H]pyrido[3,4-b]indol]-19-one

Molecular Weight	784.87
Formula	C41H44N4O10S
CAS No.	497871-47-3 (Lurbinectedin);
Chemical Name	Spiro[6,16-(epithiopropanoxymethano)-7,13-imino-12H-1,3-dioxolo[7,8]isoquino[3,2-b][3]benzazocine-20,1′-[1H]pyrido[3,4-b]indol]-19-one, 5-(acetyloxy)-2′,3′,4′,6,6a,7,9′,13,14,16-decahydro-8,14-dihydroxy-6′,9-dimethoxy-4,10,23-trimethyl-, (1’R,6R,6aR,7R,13S,14S,16R)- (9CI)

fda approved , 6/15/2020,ZEPZELCA, Pharma Mar S.A.

To treat metastatic small cell lung cancer
Drug Trials Snapshot

Research Code：PM-01183;PM-1183

MOA：RNA polymerase inhibitor

Indication：Ovarian cancer;Breast cancer;Non small cell lung cancer (NSCLC)лурбинектединلوربينيكتيدين芦比替定(1R,1’R,2’R,3’R,11’S,12’S,14’R)-5′,12′-Dihydroxy-6,6′-dimethoxy-7′,21′,30′-trimethyl-27′-oxo-2,3,4,9-tetrahydrospiro[β-carboline-1,26′-[17,19,28]trioxa[24]thia[13,30]diazaheptacyclo[12.9.6.1^3,11…^2,13.0^4,9.0^15,23.0^16,20]triaconta[4,6,8,15,20,22]hexaen]-22′-yl acetate[ACD/IUPAC Name]2CN60TN6ZS497871-47-3[RN]9397

Lurbinectedin is in phase III clinical development for the treatment of platinum refractory/resistant ovarian cancer.

Phase II clinical trials are also ongoing for several oncology indications: non-small cell lung cancer, breast cancer, small cell lung cancer, head and neck carcinoma, neuroendocrine tumors, biliary tract carcinoma, endometrial carcinoma, germ cell tumors and Ewing’s family of tumors.

Lurbinectedin, sold under the brand nameZepzelca, is a medication for the treatment of adults with metastatic small cell lung cancer (SCLC) with disease progression on or after…

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AK 3280

New Drug Approvals

AK-3280

AK 3280; GDC3280; RG 6069

C₁₉ H₁₅ F₃ N₄ O_2, 388.34

CAS 1799412-33-1

4H-Benzimidazol-4-one, 1,5-dihydro-1-methyl-7-(1-methyl-1H-pyrazol-4-yl)-5-[4-(trifluoromethoxy)phenyl]-

Ci8Hi₄N50₂F₃, mass 389.3 g/mol),

ROCHE,

Ark Biosciences , under license from Roche , is developing AK-3280, an antifibrotic agent, for the potential oral treatment of IPF. In July 2018, Ark intended to further clinical development of the drug, for IPF. In June 2019, a phase I trial was planned in Sweden.

• Originator Genentech
• Mechanism of Action Undefined mechanism

• Phase I Interstitial lung diseases

• 19 Jun 2019Ark Biosciences plans a phase I trial for Idiopathic pulmonary fibrosis (In volunteers) in Sweden (PO, Tablet), in August 2019 , (NCT03990688)
• 28 Sep 2018GDC 3280 is still in phase I trials for Interstitial lung diseases (Genentech pipeline, September 2018)
• 28 Jun 2018No recent reports of development identified for phase-I development in Fibrosis(In…

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SRT 1720

New Drug Approvals

SRT-1720 diHCl

CAY10559

CAS: 1001645-58-4 (di HCl) , 925434-55-5 (free base)   1001645-58-4 (HCl)
Chemical Formula: C25H25Cl2N7OS
Molecular Weight: 542.483
Elemental Analysis: C, 55.35; H, 4.65; Cl, 13.07; N, 18.07; O, 2.95; S, 5.91

SRT-1720 HCl, SRT-1720 hudrochloride; SRT1720; SRT-1720; SRT 1720; CAY10559; CAY-10559; CAY 10559; SIRT-1933; SIRT 1933; SIRT1933.

 N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)quinoxaline-2-carboxamide dihydrochloride

• Molecular FormulaC₂₅H₂₃N₇OS
• Average mass469.561 Da

SRT-1720, also known as CAY10559 and is a drug developed by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1. It has similar activity in the body to the known SIRT1 activator resveratrol, but is 1000x more potent. In animal studies it was found to improve insulin sensitivity and lower plasma glucose levels in fat, muscle and liver tissue, and increased mitochondrial and metabolic function. A study of SRT1720 conducted by the National Institute on Aging found that the drug may extend the lifespan…

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Thiotepa, チオテパ ,тиотепа , ثيوتيبا , 塞替派 ,

New Drug Approvals

Thiotepa, チオテパ

• Use:antineoplastic, alkylating agent
• Chemical name:1,1′,1”-phosphinothioylidynetrisaziridine
• Formula:C₆H₁₂N₃PS

• MW:189.22 g/mol
• CAS:52-24-4
• EINECS:200-135-7
• LD₅₀:14500 μg/kg (M, i.v.); 38 mg/kg (M, p.o.);
  9400 μg/kg (R, i.v.)
• Aziridine, 1,1′,1”-phosphinothioylidynetris-
  Aziridine, 1-[bis(1-aziridinyl)phosphinothioyl]-
  N,N’,N”-Triethylenethiophosphoramide
  Phosphorothioic tri(ethyleneamide)

  SZ2975000

  T3NTJ APS&- AT3NTJ&- AT3NTJ [WLN]

  Thiofozil

  Thiotef

  1,1′,1”-Phosphorothioyltriaziridine

JAPAN APPROVED, Rethio, PMDA, 2019/3/26

тиотепа [Russian] [INN]

ثيوتيبا [Arabic] [INN]

塞替派 [Chinese] [INN]

Thiotepa (INN,^[1] chemical name: N,N′,N′′-triethylenethiophosphoramide) is an alkylating agent used to treat cancer.

Thiotepa is an organophosphorus compound with the formula SP(NC₂H₄)₃.^[2] It is an analog of N,N′,N′′-triethylenephosphoramide (TEPA), which contains tetrahedral phosphorus and is structurally akin to phosphate. It is manufactured by heating aziridine with thiophosphoryl chloride.

History

Thiotepa was developed…

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Acefylline

New Drug Approvals

Acefylline

• Molecular FormulaC₉H₁₀N₄O₄
• Average mass238.200 Da

(1,3-Dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)acetic acid

1,2,3,6-Tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic Acid

1,3-Dimethylxanthine-7-acetic acid

211-490-2 [EINECS]

652-37-9 [RN]

7-(Carboxymethyl)theophylline

7H-Purine-7-acetic acid, 1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-

CAS Registry Number: 652-37-9

CAS Name: 1,2,3,6-Tetrahydro-1,3-dimethyl-2,6-dioxopurine-7-acetic acid

Additional Names: carboxymethyltheophylline; 7-theophyllineacetic acid

Molecular Formula: C9H10N4O4

Molecular Weight: 238.20

Percent Composition: C 45.38%, H 4.23%, N 23.52%, O 26.87%

Literature References: Prepn: DE 352980 (1922 to E. Merck); Frdl. 14, 1320; S. M. Ride et al., Pharmazie 32, 672 (1977). Prepn of salts: J. Baisse, Bull. Soc. Chim. Fr. 1949, 769; M. Milletti, F. Virgili, Chimica 6, 394 (1951), C.A. 46, 8615h (1952). GC determn in urine: J. Zuidema, H. Hilbers, J. Chromatogr. 182, 445 (1980). HPLC determn in serum and pharmacokinetics: S. Sved et al.,Biopharm. Drug Dispos. 2, 177 (1981).

Properties: Crystals from water, mp 271°.

Melting point: mp…

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Structural evolution of carbon in an Fe@C catalyst during the Fischer–Tropsch synthesis reaction

Shuai Lyu,^ab  Chengchao Liu,^b  Guanghui Wang,*^a  Yuhua Zhang,^b  Jinlin Li^b  and  Li Wang*^b 

 Author affiliations

*Corresponding authors

^aHubei Key Laboratory of Coal Conversion and New Carbon Material, School of Chemical Engineering and Technology, Wuhan University of Science and Technology, Wuhan 430081, China
E-mail: wghwang@263.net

^bKey Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission & Ministry of Education, South-Central University for Nationalities, Wuhan 430074, China
E-mail: li.wang@mail.scuec.edu.cn

Abstract

A pseudo-in situ research method was applied to provide insight into the structural evolution of carbon in an Fe@C catalyst at different stages of the Fischer–Tropsch reaction. Five typical stages of the catalyst were selected for in-depth structural investigation; these were: the fresh catalyst, reduced catalyst, and catalyst in the stable conversion period, in an increased-conversion period and at the inactivation stage. The results indicated that the integral structure of Fe@C constantly changed in the Fischer–Tropsch reaction. Iron carbide transformed from the Fe phase that was easily oxidized under high temperature Fischer–Tropsch conditions, and the carbon framework was completely destroyed in the reaction process, leading to a drastic decrease in the specific surface area of the material. This destruction could have two opposing effects: on the one hand, the loss of carbon could re-expose the active sites that have been covered by carbon at a reaction temperature of 320 °C and favor the reaction; on the other hand, the deposition of carbon could block the active sites and lead to inactivation when the reaction temperature is over 340 °C.

https://pubs.rsc.org/en/Content/ArticleLanding/2019/CY/C8CY02420K?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2Fcy+%28RSC+-+Catalysis+Science+%26+Technology+latest+articles%29#!divAbstract

////////Fischer–Tropsch

Eco-friendly decarboxylative cyclization in water: practical access to the anti-malarial 4-quinolones

Abstract

An environmentally benign decarboxylative cyclization in water has been developed to synthesize 4-quinolones from readily available isatoic anhydrides and 1,3-dicarbonyl compounds. Isatins are also compatible for the reaction to generate 4-quinolones in the presence of TBHP in DMSO. This protocol provides excellent yields under mild conditions for a broad scope of 4-quinolones, and has good functional group tolerance. Only un-harmful carbon dioxide and water are released in this procedure. Moreover, the newly synthesized products have also been selected for anti-malarial examination against the chloroquine drug-sensitive Plasmodium falciparum 3D7 strain. 3u is found to display excellent anti-malarial activity with an IC₅₀ value of 33 nM.

Eco-friendly decarboxylative cyclization in water: practical access to the anti-malarial 4-quinolones

Yue Ma,^a  Yongping Zhu,^a  Dong Zhang,^a  Yuqing Meng,^a  Tian Tang,^a  Kun Wang,^a  Ji Ma,^a  Jigang Wang^a  and  Peng Sun*^a 

 Author affiliations

*Corresponding authors

^aArtermisinin Research Center and Institute of Chinese Meteria Medica, Academy of Chinese Medical Sciences, Beijing, P. R. China
E-mail:psun@icmm.ac.cn

https://pubs.rsc.org/en/Content/ArticleLanding/2019/GC/C8GC03570A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

ethyl 2-(4-(benzyloxy)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (3u) White solid, m.p. 288-289 oC;

1H NMR (600 MHz, DMSO-d6) δ 12.14 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.72 (ddd, J = 8.4, 7.1, 1.5 Hz, 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.52 (td, J = 8.5, 1.7 Hz, 1H), 7.43 – 7.35 (m, 4H), 7.29 – 7.21 (m, 4H), 7.10 (td, J = 7.5, 0.5 Hz, 1H), 5.17 (s, 2H), 3.91 (q, J = 7.1 Hz, 2H), 2.00 (s, 1H), 0.83 (t, J = 7.1 Hz, 3H) ppm;

13C NMR (150 MHz, DMSO-d6) δ 174.1, 166.2, 156.2, 148.0, 139.8, 137.2, 132.8, 132.0, 130.5, 129.4, 128.7, 128.2, 127.6, 125.5, 125.2, 124.3, 123.6, 120.9, 118.9, 116.4, 115.8, 113.5, 70.2, 60.2, 14.0 ppm;

HRMS (ESI) calcd for [C25H21NO4+H]+ 400.1471, found 400.1463.

 

////////

Development of an SNAr Reaction: A Practical and Scalable Strategy To Sequester and Remove HF

ORGANIC CHEMISTRY SELECT

A simple and operationally practical method to sequester and remove fluoride generated through the S_NAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubber of the hydrofluoric acid byproduct, which is simply precipitated and filtered from the reaction mixture during standard aqueous workup. The method has been tested from 10 to 100 g scale of operation, showing >99.5% decrease in fluoride content in each case. Full mass recovery of calcium fluoride is demonstrated at both scales, proving this to be a general, efficient, and robust method of fluoride abstraction to help prevent corrosion of glass-lined reactors.

A. John Blacker*^† , Gabriel Moran-Malagon^†, Lyn Powell^‡, William Reynolds^†, Rebecca Stones^†, and 

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Development of an SNAr Reaction: A Practical and Scalable Strategy To Sequester and Remove HF

A simple and operationally practical method to sequester and remove fluoride generated through the S_NAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubber of the hydrofluoric acid byproduct, which is simply precipitated and filtered from the reaction mixture during standard aqueous workup. The method has been tested from 10 to 100 g scale of operation, showing >99.5% decrease in fluoride content in each case. Full mass recovery of calcium fluoride is demonstrated at both scales, proving this to be a general, efficient, and robust method of fluoride abstraction to help prevent corrosion of glass-lined reactors.

A. John Blacker*^† , Gabriel Moran-Malagon^†, Lyn Powell^‡, William Reynolds^†, Rebecca Stones^†, and Michael R. Chapman^†

^† Institute of Process Research and Development, School of Chemistry and School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, United Kingdom

^‡ Chemical Development, AstraZeneca, Macclesfield SK10 2NA, United Kingdom

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00090

*E-mail: j.blacker@leeds.ac.uk.

///////////////aryl amines, calcium fluoride, fluoride sequestration, scale-up, S_NAr reaction,

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

National award to Anthony Melvin Crasto for contribution to Pharma society from Times Network for Excellence in HEALTHCARE) | 5th July, 2018 | Taj Lands End, Mumbai, India

DR ANTHONY MEVIN CRASTO Conferred prestigious individual national award at function for contribution to Pharma society from Times Network, National Awards for Marketing Excellence ( For Excellence in HEALTHCARE) | 5th July, 2018 | Taj Lands End, Mumbai India

 

////////////National award,  contribution to Pharma society, Times Network, Excellence in HEALTHCARE,  5th July, 2018, Taj Lands End, Mumbai,  India, ANTHONY CRASTO

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