Month: June 2015

Controlling Residual Arylboronic Acids as Potential Genotoxic Impurities in APIs

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

DRUG REGULATORY AFFAIRS INTERNATIONAL

Arylboronic acids, but not the corresponding deboronated arenes, recently have been found to be weakly mutagenic in microbial assays [1].  Hence arylboronic acids may be considered potentially genotoxic impurities, and controlling the levels of residual arylboronic acids in APIs could become a regulatory requirement.  The issues should be decided by toxicology studies for the specific arylboronic acids in question.

Several approaches have been successful in removing boronic acids.  Diethanolaminomethyl polystyrene (DEAM-PS) [2],[3] and immobilized catechol [4] have been used to scavenge boronic acids.  Complex formation with diethanolamine may solubilize residual boronic acids in mother liquors.  Since arylboronic acids ionize similarly to phenols, basic washes of an API solution may remove arylboronic acids.  A selective crystallization can purge an arylboronic acid from the API.

The best means to control residual aryl boronic acids in APIs at the ppm level may be to decompose them through deboronation.  Sterically hindered, electron-rich aryl boronates…

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ML-236B, Mevastatin (compactin)

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

Mevastatin2DCSD.svgMevastatin (compactin, ML-236B) is a hypolipidemic agent that belongs to the statins class.

It was isolated from the mold Penicillium citrinum by Akira Endo in the 1970s, and he identified it as a HMG-CoA reductase inhibitor,[1] i.e., a statin. Mevastatin might be considered the first statin drug;[2] clinical trials on mevastatin were performed in the late 1970s in Japan, but it was never marketed.[3] The first statin drug available to the general public was lovastatin.

In vitro, it has antiproliferative properties.[4]

A British group isolated the same compound from Penicillium brevicompactum, named it compactin, and published their results in 1976.[5] The British group mentions antifungal properties with no mention of HMG-CoA reductase inhibition.

High doses inhibit growth and proliferation of melanoma cells.[6]

Systematic (IUPAC) name
(1S,7R,8S,8aR)-8-{2-[(2

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AG 014699, Rucaparib

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

AG014699AG014699, 


AG014699, the phosphate salt of AG14447, which has improved aqueous solubility, has been selected for clinical trial.AG014699 is a tricyclic indole poly(ADP-Ribose) polymerase (PARP) inhibitor with potential antineoplastic activity.


M.Wt: 421.3593
Formula: C19H21FN3O5P
CAS No: 459868-92-9

Figure

Rucaparib, PF-01367338283173-50-2  cas 6H-​Pyrrolo[4,​3,​2-​ef]​[2]​benzazepin-​6-​one, 8-​fluoro-​1,​3,​4,​5-​tetrahydro-​2-​[4-​[(methylamino)​methyl]​phenyl]​-6H- ​Azepino[5,​4,​3-​cd]​indol-​6-​one, 8-​fluoro-​1,​3,​4,​5-​tetrahydro-​2-​[4-​[(methylamino)​methyl]​phenyl] ​-8-​Fluoro-​2-​[4-​[(methylamino)​methyl]​phenyl]​-​1,​3,​4,​5-​ tetrahydro-​6H-​azepino[5,​4,​3-​cd]​indol-​6-​one;8-Fluoro-2-(4-methylaminomethyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one8-Fluoro-2-(4-methylaminomethyl-phenyI)-l,3,4,5-tetrahydro-azepino[5,4,3- cd]indol-6-one

MW..C19 H18 F N3 O
cas of csa salt—–1327258-57-0
773059-19-1 (hydrochloride)
773059-22-6 (L-tartrate)
773059-23-7 (acetate)
459868-92-9  PHOSPHATE
AG-014699
AG-14699
CO-338
PF-01367338
AG-014447 (free base)
AG-14447 (free base) 
Agouron (Originator)
Pfizer (Originator)
Clovis Oncology
WO 2014052550, WO 2014037313, WO 2000042040WO 2004087713WO 2005012305

Rucaparib (AG 014699) is a PARP inhibitor being investigated as a potential anti-cancer agent.

Rucaparib inhibits “the contraction of isolated vascular smooth muscle, including that from the tumours of cancer patients. It also reduces the migration of some cancer and normal cells in culture.”[1]

It can be taken orally in tablet form.[2]

It…

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7 LAKH VIEWS ON THIS BLOG……NEW DRUG APPROVALS

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

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Scalable Access to Aeruginosins

DR ANTHONY MELVIN CRASTO Ph.D spectroscopy, STRUCTURE ELUDICATION, Synthesis

thumbnail image: Scalable Access to Aeruginosins

Scalable Access to Aeruginosins

Palladium-catalyzed C–H activation reactions

Read more

http://www.chemistryviews.org/details/ezine/7956351/Scalable_Access_to_Aeruginosins.html

 

 

http://www.mdpi.com/1660-3397/13/4/2347

 

 

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Missing out on discoveries

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

amphoteros

Scientists make discoveries all the time. Research findings differ in terms of significance, breadth, and downstream potential, but they do happen on a daily basis to everyone who is passionate about research. Any undergraduate student who is just getting into the “research groove” is a good example. The fact that the majority of his/her discoveries early on are not going to impress the community-at-large is not important. What is critical is to get into the habit of noticing interesting things, even if they are not earth-shattering. Upon training, one gets to appreciate the finer details, which inevitably leads to significant findings.

Now let’s consider someone who has just made a truly thought-provoking discovery. Here is a question that interests me: how often have others passed by that observation and did not even think twice about its significance? One can probably say that the predecessors might not have had the right tools, which…

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Pirarubicin Hydrochloride 

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

Pirarubicin Hydrochloride  

(7S,9S)-7-((2R,4S,5S,6S)-4-amino-6-methyl-5-((R)-tetrahydro-2H-pyran-2-yloxy)-tetrahydro-2H-pyran-2-yloxy)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione HCl

(CAS 95343-20-7)

THP Hydrochloride

(7S,9S)-7-((2R,4S,5S,6S)-4-amino-6-methyl-5-((R)-tetrahydro-2H-pyran-2-yloxy)-tetrahydro-2H-pyran-2-yloxy)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione HCl

MF C32H38ClNO12

MW 664.1

BASE 72496-41-4

Pirarubicin
or Pinorubicin
or Therarubicin
or (8S,10S)-10-(((2R,4S,5S,6S)-4-Amino-6-methyl-5-(((R)-tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione
or Pirarubicin

Pirarubicin Hcl is an analogue of the anthracycline anti-neoplastic doxorubicin, which is an inhibitor of Topo II.
Target: Topoisomerase
Pirarubicin is an anthracycline drug. An analogue of the anthracycline antineoplastic antibiotic doxorubicin. Pirarubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. This agent is less cardiotoxic than doxorubicin and exhibits activity against some doxorubicin-resistant cell lines.

File:Pirarubicin.png

Pirarubicin (THP-adriamycin or THP-doxorubicin) was found during a search of new anthracycline antibiotics among 4′-O-substituted compounds having less toxicities than other anthracycline anticancer drugs in 1979 by Umezawa et al. In its preclinical…

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(1S)-(-)-beta-Pinene

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

(1S)-(1)-beta-Pinene Structure

(1S)-(1)-beta-Pinene, (1S)-(-)-beta-Pinene

.

image of (1s)-(-)-b-pinene.

image of (1s)-(-)-b-pinene

13C NMR

.

image of (1s)-(-)-b-pinene.

APT

image of (1s)-(-)-b-pinene.

DEPT

image of (1s)-(-)-b-pinene.

COSY

image of (1s)-(-)-b-pinene.

HETCOR

image of (1s)-(-)-b-pinene

IR

MASS

.

.

RAMAN

CAS No.18172-67-3
Chemical Name:(1S)-(1)-beta-Pinene
Synonyms:β-Pinen;FEMA 2903;PINENE BETA;(1S)-(-)-B-PINENE;LAEVO-BETA-PINENE;(1s)-(-)-á-pinene;ALPHA,BETA-PINENE;(1S)-(-)-SS-PINENE;PINENE, (1S)-(-)-B-;(1s)-(1)-beta-pinene
CBNumber:CB8270232
Molecular Formula:C10H16
Formula Weight:136.23
MOL File:18172-67-3.mol
(1S)-(1)-beta-Pinene Property
mp :−61 °C(lit.)
bp :165-167 °C(lit.)
alpha :-18.5 º (c=neat 25 ºC)
density :0.866 g/mL at 25 °C
vapor density :4.7 (vs air)
vapor pressure :~2 mm Hg ( 20 °C)
FEMA :2903
refractive index :n20/D 1.478
Fp :91 °F
storage temp. :2-8°C
Water Solubility :insoluble
Merck :14,7446
BRN :2038282
CAS DataBase Reference:18172-67-3(CAS DataBase Reference)
NIST Chemistry Reference:Bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-, (1S)-(18172-67-3)
EPA Substance Registry System:Bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-, (1S,5S)-(18172-67-3)
Safety
Hazard Codes :Xn,N,Xi
Risk Statements :10-20/21/22-36/37/38-43-51-65-51/53
Safety Statements :16-26-36/37-46-61-62
RIDADR :UN 2319 3/PG 3
WGK Germany :3
RTECS :DT5077000
HazardClass :3
PackingGroup :III
HS Code :29021910

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Amalner,  Jalgaon, Maharashtra, India

Amalner – Wikipedia, the free encyclopedia

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BMS 564929, Androgen receptor (AR) modulator

DR ANTHONY MELVIN CRASTO Ph.D Synthesis

New Drug Approvals

BMS-564,929.svg

BMS-564929.png

BMS-564929; BMS564929; 627530-84-1; 2-Chloro-4-[(7r,7as)-7-Hydroxy-1,3-Dioxotetrahydro-1h-Pyrrolo[1,2-C]imidazol-2(3h)-Yl]-3-Methylbenzonitrile; hydantoin,

CAS 627530-84-1, Squibb Bristol Myers Co

Molecular Formula:C14H12ClN3O3
Molecular Weight:305.71638 g/mol

4-[(7R,7aS)-7-Hydroxy-1,3-dioxoperhydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

7-K,7aS)-2-Chloro-4-(7-hydroxy-l,3-dioxotetrahydropyrrolo[l,2- c]imidazol-2-yl)-3-methylbenzonitrile

4-[(7R,7aS)-7-hydroxy-1,3-dioxo-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

BMS-564929 is a highly potent, orally active and nonsteroidal tissue selective modulator of androgen receptor (AR) with Ki value of 2.11 nM.

BMS-564929 is a selective androgen receptor (AR) modulator with Ki value of 2.11 ± 0.16 nM [1].
The AR is a type of nuclear receptor that is activated by the androgenic hormones, testosterone, or dihydrotestosterone. The important function is regulating gene expression.
BMS-564929 is a muscle-tissue specific agonist for AR with a bicyclic hydantoin structure [2]. BMS-564929 is about 400-fold selective for AR vs. PR and more than 1000-fold selective for AR vs. GR, MR and ERα and β. In the C2C12 myoblast cell line, BMS-564929 shows a potency of 0.44 ± 0.03 nM compared with…

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