Month: May 2015

ZSTK 474

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

ZSTK474

4-[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]morpholine

ZSTK474; 475110-96-4; 4,4′-(6-(2-(Difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine; ZSTK-474; ZSTK 474; TCMDC-137004;

2-(2-Difluoromethylbenzimidazol-1-yl)-4,6-bis(morpholino)-1,3,5-triazine

2-(2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine

Zenyaku Kogyo (Innovator)

phase2………Treatment of Solid Tumors Therapy

ZSTK474 is a cell permeable and reversible P13K inhibitor with an IC₅₀ at 6nm. It was identified as part of a screening library, selected for its ability to block tumor cell growth. ZSTK474 has shown strong antitumor activities against human cancer xenographs when administered orally to mice without a significant toxic effect.

Phosphatidylinositol 3-kinase (PI3K) has been implicated in a variety of diseases including cancer. A number of PI3K inhibitors have recently been developed for use in cancer therapy. ZSTK474 is a highly promising antitumor agent targeting PI3K. We previously reported that ZSTK474 showed potent inhibition against four class I PI3K isoforms but not against 140 protein kinases.

However, whether ZSTK474 inhibits DNA-dependent protein kinase (DNA-PK), which is structurally similar to PI3K, remains unknown. To investigate the inhibition of DNA-PK, we developed a…

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Lascufloxacin, KRP-AM1977, by Kyorin

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

Figure JPOXMLDOC01-appb-C000001

2D chemical structure of 848416-07-9

Lascufloxacin

CAS 848416-07-9

Kyorin Pharmaceutical Co., Ltd., 杏林製薬株式会社

3-Quinolinecarboxylic acid, 7-((3S,4S)-3-((cyclopropylamino)methyl)-4-fluoro-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-8-methoxy-4-oxo-

7-((3S,4S)-3-((Cyclopropylamino)methyl)-4-fluoropyrrolidin-1-yl)-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

{(3S, 4S) -3 – [(cyclopropylamino) methyl] -4-fluoro-1-yl} -6-fluoro-1- (2 – fluoroethyl) -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

 

(KRP-AM1977X)

  • C21-H24-F3-N3-O4
  • 439.4316
  • SMILES……COc1c2c(cc(c1N3C[C@H](C(C3)CNC4CC4)F)F)c(=O)c(cn2CCF)C(=O)O

…………………………

Lascufloxacin hydrochloride

2D chemical structure of 1433857-09-0

  • C21-H24-F3-N3-O4.Cl-H
  • 475.8925
  • CAS 1433857-09-0

3-Quinolinecarboxylic acid, 7-((3S,4S)-3-((cyclopropylamino)methyl)-4-fluoro-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-8-methoxy-4-oxo-, hydrochloride (1:1)

……………….

Lascufloxacin mesylate2D chemical structure of 1433857-41-0

3-Quinolinecarboxylic acid, 7-((3S,4S)-3-((cyclopropylamino)methyl)-4-fluoro-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-8-methoxy-4-oxo-, methanesulfonate (1:1)

  • C21-H24-F3-N3-O4.C-H4-O3-S
  • 535.5372
  • CAS 1433857-41-0

The other non-fluorinated quinolone under clinical development is KRP-AM1977, by Kyorin, which is in Phase I of clinical trials. The oral formulation of the compound (KRP-AM1977X) is being tested for treatment of respiratory infections and the I.V. formulation is under development for treatment of MRSA infections [1,2].

………………………………..

PATENT

WO 2013069297

http://www.google.co.in/patents/WO2013069297A1?cl=en

The present invention is represented by Formula (1) – {(3S, 4S) -3 – [(cyclopropylamino) methyl] -4-fluoro-1-yl} -6-fluoro-1- (2 – fluoroethyl) -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (hereinafter, compound (1) crystals of a salt also referred to), and a method for their preparation.

Figure JPOXMLDOC01-appb-C000001

Typically, the pharmaceutical, in addition…

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CARMEN DRAHL….Tribute to a Great Writer

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

CARMEN DRAHL

Award-winning science communicator and social media power user based in Washington, DC.

Specialties:
interviewing, science writing, social media, Twitter, Storify, YouTube,
public speaking, hosting, video production, iPhone videography,
non-linear video editing, blogging (WordPress and Blogger), HTML website
coding

We have been reading her for the past several years and a inspiration for many

Links

Carmen Drahl (@carmendrahl) | Twitter

www.linkedin.com/in/carmendrahl/en

http://www.ddn-news.com/

http://cenblog.org/the-safety-zone/

Carmen Drahl – Google+

Carmen Drahl

Education

Princeton University

Ph.D., Chemistry

2002 – 2007

Ph.D. with Erik J. SorensenShe was on a team that completed the first total synthesis of
abyssomicin C, a molecule found in small quantities in nature that
showed hints of promise as a potential antibiotic. I constructed
molecular probes from abyssomicin for proteomics studies…

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Motesanib (AMG-706)

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

Motesanib (AMG-706)

Amgen Inc.

Motesanib.svg

Motesanib (AMG 706) is an experimental drug candidate originally developed by Amgen[1] but is now being investigated by theTakeda Pharmaceutical Company. It is an orally administered small molecule belonging to angiokinase inhibitor class which acts as an antagonist of VEGF receptors, platelet-derived growth factor receptors, and stem cell factor receptors.[2] It is used as thephosphatesalt motesanib diphosphate.

Motesanib, also known as AMG-706, is an orally administered multikinase inhibitor that selectively targets VEGF receptors, platelet-derived growth factor receptors, and Kit receptors.

Clinical trials

Motesanib was originally investigated for effectiveness against advanced nonsquamous non-small-cell lung cancer (NSCLC), withPhase II trials indicating an effectiveness comparable to bevacizumab when they were both used in combination withpaclitaxel/carboplatin.[3] However a later and more detailed Phase III trial failed to show any benefit for the treatment of NSCLC.

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Allisartan isoproxil

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

Figure US20100292286A1-20101118-C00007

Allisartan isoproxil

CAS: 947331-05-7

553.01, C27 H29 Cl N6 O5

Shanghai Allist Pharmaceutical, Inc.

Allist Shanghai Pharmaceutical Co., Ltd.

2-butyl-4-chloro-1-[2′-(1H-tetrazol-5-yl)-1,1′-biphenyl-methyl]-imidazole-5-carboxylic acid, 1-[(isopropoxy)-carbonyloxy] methyl ester,

2-Butyl-4-chloro-1-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-imidazole-5-carboxylic acid isopropoxycarbonyloxymethyl ester

2-butyl-4-chloro-1-[2′-(1H-tetrazol-5-yl)1,1′-biphenyl-methyl]imidazole-5-carboxylic acid, 1-[(isopropoxycarbonyl)oxy]methyl ester

Allisartan is an orally-available angiotensin AT1 antagonist in phase II clinical trials at Shanghai Allist Pharmaceutical for the treatment of mild to moderate essential hypertension.

Shanghai Allist Pharmaceutical PHASE 2 for Hypertension

The prior art discloses Arleigh medoxomil illiquid, low bulk density, electrostatic phenomena evident. Chinese patent discloses a CN200710094131.0 Alicante medoxomil polymorph and method of preparation. Allie medoxomil based crystal prepared by the method has high stability characteristics, but relatively small bulk density of the crystal clear after the electrostatic phenomenon and poor liquidity dried, crushed and used for easy dispensing generate dust, operating the site clean and labor protection inconvenience, on the other hand also for accurate weighing and packaging products inconvenience.

CN200710094021.4 and CN201110289695.6 disclose the preparation…

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Enantioselective α-amination of 1,3-dicarbonyl compounds in batch and flow with immobilized thiourea organocatalysts

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

Green Chemistry International

Enantioselective α-amination of 1,3-dicarbonyl compounds in batch and flow with immobilized thiourea organocatalysts

*Corresponding authors
aInstitute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain
bDepartament de Química Orgànica, Universitat de Barcelona, 08080 Barcelona, Spain
Green Chem., 2015, Advance Article

A PS-immobilized thiourea catalyses the enantioselective [small alpha]-amination of dicarbonyl compounds at room temperature. It is not deactivated by azodicarboxylate reagents, allowing multiple recycling in batch as well as use in flow (21 min residence time).
DOI: 10.1039/C5GC00496A

A polymer-supported bifunctional thiourea organocatalyst (PS-TU) has been prepared and successfully used in the enantioselective α-amination of 1,3-dicarbonyl compounds with azodicarboxylates. In contrast to homogeneous thioureas, PS-TU is not irreversibly deactivated by the azodicarboxylate reagents, and simple washing with triethylamine…

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Cyclopentyl methyl ether-NH4X: a novel solvent/catalyst system for low impact acetalization reactions

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

Green Chemistry International

Green Chem., 2015, Advance Article
*Corresponding authors
aDipartimento di Chimica e Farmacia, Università di Sassari, via Vienna 2, 07100 – Sassari, Italy
E-mail: ugo@uniss.it
Green Chem., 2015, Advance Article

DOI: 10.1039/C5GC00465A

Cyclopentyl methyl ether and ammonium salts provide an environmentally friendly reaction medium for the synthesis of acetals.
Cyclopentyl methyl ether-NH4X: a novel solvent/catalyst system for low impact acetalization reactions
Cyclopentyl methyl ether, a low impact ether forming a positive azeotrope with water, was successfully employed as a solvent in the synthesis of 1,3-dioxanes and 1,3-dioxolanes carried out under Dean-Stark conditions by the acetalization of aliphatic and aromatic aldehydes or ketones, employing ammonium salts as environmentally friendly acidic catalysts.

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Strain-Driven Direct Cross-Aldol and -Ketol Reactions of Four-Membered Heterocyclic Ketones

DR ANTHONY MELVIN CRASTO Ph.D ORGANIC CHEMISTRY, Synthesis , ,

Figure

Strain-Driven Direct Cross-Aldol and -Ketol Reactions of Four-Membered Heterocyclic Ketones

Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1519 Budapest, Hungary
Org. Lett., Article ASAP
DOI: 10.1021/acs.orglett.5b01002

Owing to the ring strain and α-heteroatom effect, the four-membered heterocyclic ketones can undergo direct cross-aldol and -ketol reactions without the need for preformed enol or “enolate-like” intermediates. Besides the organocatalyzed cross-ketol addition onto their highly active carbonyl group, their ability to act as a nucleophilic donor has also been explored. As a result, a number of discrete aldol adducts were synthesized and the distinct reactivities were successfully combined into a double-aldol one-pot reaction.

Budapest, Hungary

Budapest is the largest city and also the capital of Hungary. It is the principal transportation, industrial, commercial, …

Map of budapest hungary

danube

Championed first by the Ottomans, Budapest’s famed thermal baths include the sprawling, baroque Széchenyi Baths in City Park.

ANAGLIPTIN Spectral visit

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide

N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide
CAS No.:739366-20-2
Synonyms:
  • Anagliptin;
Formula:C19H25N7O2
Exact Mass:383.20700

Anagliptin chemically known as N-[2-[2-[2(S)-cyanopyrrolidin-l-yl]-2-oxoethylamino]- 2-methylpropyl]-2-methylpyrazolo[l,5-a]pyrimidine-6-carboxamide is represented by the structural formula:

Figure imgf000003_0001

Anagliptin is a dipeptidyl peptidase IV- inhibitor. United States Patent No 7345 1 80- (IJS’ 180) discloses anagliptin.

N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide NMR spectra analysis, Chemical CAS NO. 739366-20-2 NMR spectral analysis, N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide H-NMR spectrumN-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide NMR spectra analysis, Chemical CAS NO. 739366-20-2 NMR spectral analysis, N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide C-NMR spectrum

Example 5: Synthesis of N-[2-2[2(S)-Cyano pyrrolidin-l-yl]-2-oxoethyIamino]-2- methyIpropyl]-2-methyaIpyrazoIo [1, 5-a] pyrimidine-6-carboxamide (I, anagliptin).

1H NMR (300 MHz, CDC13): δ 1.16 (s, 6H), 2.23(m, 4H), 2.54(s, 3H), 3.25-3.51 (m, 6H), 4.78 (m, 1H), 6.53 (s, 1H), 8.05 (s, 1H), 8.93 (s, 1H), 9.22(s, 1H)

HPLC Purity: 99.71%, Chiral purity: 100%………WO2014147640A2

Kato, M.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Makino, M.; Takeda, M.; Mirensha, Y.;
Kakigami, T. Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-
2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective
DPP-IV inhibitor. Bioorg. Med. Chem. 2011, 19, 7221–7227.

http://www.sciencedirect.com/science/article/pii/S0968089611007784

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LATUR, MAHARASHTRA, INDIA

http://en.wikipedia.org/wiki/Latur

Latur
लातूर
Lattalur…

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