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GDC 0853, Fenebrutinib

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product image (CAS 1434048-34-6)Fenebrutinib.png

 

.

Picture credit….

GDC 0853, Fenebrutinib

GDC-0853; RG 7845

Molecular Formula: C37H44N8O4
Molecular Weight: 664.79646 g/mol

2-[3-(hydroxymethyl)-4-[1-methyl-5-[(7-methyl-6,8-dihydro-5H-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one

3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one

3-[3-(hydroxymethyl)-4-[5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-1H-pyridin-3-yl]-2-pyridyl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one

2H-​Cyclopenta[4,​5]​pyrrolo[1,​2-​a]​pyrazin-​1(6H)​-​one, 2-​[1,​6-​dihydro-​3′-​(hydroxymethyl)​-​1-​methyl-​5-​[[5-​[(2S) ​-​2-​methyl-​4-​(3-​oxetanyl)​-​1-​piperazinyl]​-​2-​pyridinyl]​amino]​ -​6-​oxo[3,​4′-​bipyridin]​-​2′-​yl]​-​3,​4,​7,​8-​tetrahydro-​7,​7-​ dimethyl-

s ISoMER 1434048-34-6 desired

r iSoMER 1434048-57-3 undesired

 

Phase 1

Patients with Patients with Resistant B-Cell Lymphoma or Chronic Lymphocytic Leukemia..

‘s Btk inhibitor

https://clinicaltrials.gov/ct2/show/NCT01991184

Bruton tyrosine kinase inhibitor

  • 01 Sep 2015 Phase-I clinical trials in Autoimmune disorders (In volunteers) in USA (PO, Capsule and Tablet) (NCT02699710)
  • 16 Oct 2014 Discontinued – Phase-I for Non-Hodgkin’s lymphoma (Second-line therapy or greater) in USA (unspecified route)
  • 16 Oct 2014 Discontinued – Phase-I for Chronic lymphocytic leukaemia (Second-line therapy or greater) in USA (unspecified route)

SCHEMBL14912984.png

GDC-0853; RG 7845; RO 7010939

2-[1,6-dihydro-3′-(hydroxymethyl)-1-methyl-5-[[5-[(2S)-2-methyl-4-(3-oxetanyl)-1-piperazinyl]-2-pyridinyl]amino]-6-oxo[3,4′-bipyridin]-2′-yl]-3,4,7,8-tetrahydro-7,7-dimethyl-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one

GDC-0853 is an orally bioavailable, selective, and reversible Bruton’s tyrosine kinase (BTK) inhibitor with IC50s ranging from 2-9 nM for basophil activation, B cell receptor activation, and constitutive p-BTK activity in whole blood lysates.1,2 In rats, treatment for longer than 7 days leads to pancreatic toxicity but it does not occur in mice or dogs, even at higher doses.3 Formulations containing GDC-0853 were well-tolerated in Phase I clinical trials and are in additional clinical trials for rheumatoid arthritis, lupus erythematosus, lymphoma, and leukemia.

  • Originator Genentech
  • Class Antineoplastics; Antirheumatics; Piperazines; Pyrazines; Pyridines
  • Mechanism of Action Agammaglobulinaemia tyrosine kinase inhibitors

Highest Development Phases

  • Phase II Rheumatoid arthritis; Systemic lupus erythematosus; Urticaria
  • Phase I  Autoimmune disorders
  • Discontinued Chronic lymphocytic leukaemia; Non-Hodgkin’s lymphoma

Most Recent Events

  • 01 Jun 2018 Chemical structure information added
  • 07 Nov 2017 Genentech initiates enrolment in a phase II extension trial for Systemic Lupus Erythematosus in Spain (EudraCT2017-001764-37)
  • 13 Sep 2017 Genentech initiates enrolment in a phase I trial in Healthy volunteers in United Kingdom (NCT03290703)

BTK inhibitor GDC-0853 An orally available inhibitor of Bruton’s tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, GDC-0853 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways, which leads to the inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B-lymphocyte development, activation, signaling, proliferation and survival.

Patent

WO 2013067274

https://www.google.co.in/patents/WO2013067274A1?cl=en

part

Example 271a (S)-tert-Butyl 4-(6-(5-Chloro-2-methoxypyridin-3-ylamino)pyridin-3-yl)-3-methylpiperazine-1-carboxylate 271a

Image loading...

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (40 mL), (S)-tert-butyl 4-(6-amino pyridin-3-yl)-3-methylpiperazine-1-carboxylate 101h (2.04 g, 7.0 mmol), 3-bromo-5-chloro-2-methoxypyridine (2.8 g, 12.6 mmol), Pd2(dba)3 (640 mg, 0.70 mmol), XantPhos (404.6 mg, 0.70 mmol), and cesium carbonate (4.56 g, 14.0 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 100 °C for 4 h. After this time the reaction was cooled to room temperature. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:3 ethyl acetate/petroleum ether to afford 271a (1.7 g, 57%) as a yellow solid. MS-ESI: [M+H]+ 434.2

Example 271btert-Butyl (3S)-4-(6-{[5-(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-3-(hydroxymethyl)pyridin-4-yl)-2-methoxypyridin-3-yl] amino}pyridin-3-yl)-3-methylpiperazine-1-carboxylate 271b

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 271a (650 mg, 1.50 mmol), {3-[(acetyloxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (1.79 g, 4.5 mmol), Pd2(dba)3 (137.2 mg, 0.15 mmol), P(cy)3(167.4 mg, 0.60 mmol), Cs2CO3 (978 mg, 3.0 mmol), dioxane (20 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110°C for 16 h. After this time the reaction was cooled to room temperature. Lithium hydroxide monohydrate (1.89 g, 45 mmol) and water (2.0 mL) were added. The resulting mixture was stirred at 45°C for 4 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 3:1 ethyl acetate/petroleum ether to afford 271b (290 mg, 27%) as a yellow solid. MS-ESI: [M+H]+ 709.3

Example 271c 10-[3-(Hydroxymethyl)-4-[5-({5-[(2S)-2-methylpiperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridin-2-yl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 271c

A solution of 271b (286.6 mg, 0.40 mmol) in dioxane/HCl (30 mL) was stirred at 50 °C for 2 h. It was evaporated under reduced pressure to afford 271c (450 mg, crude) as a black solid. MS-ESI: [M+H]+ 595.3

Example 271 3-[3-(hydroxymethyl)-4-[5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-1H-pyridin-3-yl]-2-pyridyl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one 271

To a solution of 271c (450 mg, 0.75 mmol) in methanol (10 mL) was added oxetan-3-one (162 mg, 2.25 mmol), NaBH3CN (141.8 mg, 2.25 mmol), and ZnCl2 (306 mg, 2.25 mmol). The reaction was stirred at room temperature for 3 h. The mixture was evaporated under reduced pressure and the residue was diluted with water (5 mL). It was then extracted with dichloromethane (3 X 10 mL) and the combined dichloromethane extract was concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 271 (23.0 mg, 8.8%, over two steps) as a yellow solid. MS-ESI: [M+H]+651.3. 1H NMR (500 MHz, CDCl3) δ 9.76 (s, 1H), 8.74 (d, J = 2.0 Hz, 1H), 8.53 (d, J = 5.0 Hz, 1H), 7.99 (d, J = 3.0 Hz, 1H), 7.84 (s, 1H), 7.73 (s, 1H), 7.41 (d, J = 4.5 Hz, 1H), 7.35 (dd, J = 2.5 Hz, 8.5 Hz, 1H), 6.87 (s, 1H), 6.85 (d, J = 9.0 Hz, 1H), 5.16-5.13 (m, 1H), 4.72-4.69 (m, 5H), 4.54-4.53 (m, 1H), 4.36-4.35 (m, 1H), 4.19-4.17 (m, 2H), 3.89-3.87 (m, 1H), 3.56-3.49 (m, 2H), 3.11-3.09 (m, 2H), 2.60-2.48 (m, overlap, 7H), 2.24-2.21 (m, 1H), 1.29 (s, 6H), 1.02 (d, J = 6.0 Hz, 3H)

Image loading...271

………………………..

syn of 191 j

is intermediateImage loading...not product, is acid

To a mixture of 4-chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 108a (500 mg, 1.46 mmol), tert-butyl alcohol (20 mL), and dichloromethane (5 mL) was added 2-methyl-2-butene (3066 mg, 43.8 mmol). An aqueous solution (8 mL) of NaClO2 (263 mg, 2.92 mmol) and NaH2PO4·2water (683 mg, 4.38 mmol) was added dropwise at -10°C and the reaction mixture was stirred at -10 °C for overnight. It was concentrated under reduced pressure and the residue was extracted with ethyl acetate (4 × 20 mL). The combined organic extract was dried over MgSO4 and concentrated. The residue was purified with reverse-phase prep-HPLC to afford 210a (315 mg, 60%) as a pale yellow solid. MS-ESI: [M+H]+ 360.1

Example 210b 2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl} -4-[1-methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carboxylic Acid 210b

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with 210a (400 mg, 1.1 mmol), (S)-1-methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 191j (536 mg, 1.1 mmol), PdCl2(dppf) (81 mg, 0.11 mmol), K3PO4 (466 mg, 2.2 mmol), sodium acetate (216 mg, 2.2 mmol), acetonitrile (10 mL), and water (0.2 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100°C for 3 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 1:3 petroleum/ethyl acetate to afford 210b as a yellow solid (306 mg, 41%). MS-ESI: [M+H]+ 679.3

construction, use your discretion

Example 130a (3S)-tert- utyl 3-methyl-4-(6-nitropyridin-3-yl)piperazine-l-carboxylate 130a

130a

Following the procedures as described for compound lOlg, reaction of 5-bromo-2-nitropyridine (10.5 g, 50 mmol), and (JS)-tert-butyl-3 -methylpiperazine- 1 -carboxylate (10.0 g, 50 mmol) afforded 130a as a yellow solid (8.05 g, 50%). LCMS: [M+H]+ 323

Example 130b (3 S)-tert-butyl-4-(6-aminopyridin-3 -yl)-3 -methylpiperazine- 1 -carboxylate 130b

130b

Following the procedures as described for compound lOlh, hydrogenation of 130a (5.8 g) afforded 130bas a brown solid (4.9 g, 96%). LCMS: [M+H]+ 293

Example 130c (3 S)-tert-Butyl-4-(6-(5 -bromo- 1 -methyl -2 -oxo- 1,2-dihydropyridin-3 -yl amino) pyridine-3 -yl)-3 -methylpiperazine- 1 -carboxylate 130c

N

Following the procedures as described for compound lOli, reaction of 130b (4.0 g) and 3,5-dibromo-l-methylpyridin-2(lH)-one (5.5 g) afforded 130c as a yellow solid (5.4 g, 83%). LCMS: [M+H]+ 478

Example 130d (3 S)-5 -Bromo- 1 -methyl-3 -(5 -(2-methylpiperazin- 1 -yl)pyridin- 2-ylamino)pyridine-2(lH)-one 130d

Following the procedures as described for compound lOlj, acidic hydrolysis of the Boc group of 130c (3.1 g) afforded 130d as a yellow solid (2.3 g, 95%). LCMS: [M+H]+ 380.

Example 130e (3 S)-5 -Bromo- 1 -methyl-3 -(5 -(2 -methyl-4-(ox etan-3-yl)piperazin-l-yl) pyridine -2-ylamino)pyridin-2(lH)-one 130e

Following the procedures as described for compound 101k, reductive amination of 130d (2.35 g) with oxetan-3-one (0.4 mL) afforded 130e as a yellow solid (2.6 g, 98%). LCMS: [M+H]+ 434.

Example 13 Of (3S)-l-methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-l-yl)pyridin-2-ylamino) -5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-2(lH)-one 130f

check pyridine ring position

A 100 mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 130e (1.0 g, 1.0 eq., 2.3 mmol), Pin2B2 (1.46 g, 2.50 eq., 5.75 mmol), Pd2(dba)3 (105 mg, 0.05 eq., 0.125 mmol), X-Phos (93 mg, 0.1 eq., 0.23 mmol), AcOK (676 mg, 3.0 eq., 6.9 mmol), and dioxane (50 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90 °C for 4 hrs, then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was washed with 3: 1 PE/EA (80 mL) to afford 130f as yellow solid (1.0 g, 90%). MS: [M+H]+ 482.

check pyridine ring position, use your discretion

Example 191h ( 3S)-5 -Bromo- 1 -methyl-3 -(5 -(2-methylpiperazin- 1 -yl)pyridin- -ylamino)pyridine-2(lH)-one 191h

Following the procedure described for compound lOlj and starting with (3S)-tert-butyl 4-(6-(5 -bromo- 1 -methyl-2-oxo- 1 ,2-dihydropyridin-3 -ylamino)pyridine-3 -yl)-3 -methyl-piperazine-l-carboxylate 191g (3.1 g, 6.5 mmol) afforded 191h as a yellow solid (2.3 g, 94%). MS-ESI: [M+H]+ 378.

Example 1 1 i (S)-5 -Bromo- 1 -methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin- 1 -yl)pyridin-2-ylamino)pyridin-2(lH)-one 191i

A mixture of (5)-5-bromo-l-methyl-3-(5-(2-methylpiperazin-l-yl)pyridin-2-ylamino)pyridin-2(lH)-one 191h (40.0 g, 106 mmol), oxetan-3-one (1 1.4 g, 159 mmol), NaBH3CN (10.0 g, 159 mmol), and zinc chloride (21.3 g, 159 mmol) in methanol (700 mL) was stirred at 50°C for 5 hours. The mixture was added to water (100 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (200 mL x 3). The combined organic layer was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 40: 1 dichloromethane /methanol to afford 191i (35 g, 73%). MS: [M+H]+ 434.

Example 191j (J5)-l-Methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-l-yl)-pyridin- -ylamino) -5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)pyridin-2(lH)-one 191j

191 i 191j

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with (5)-tert-butyl-4-(6-(5-bromo-l-methyl-2-oxo-l ,2-dihydropyridin-3-ylamino)pyridine-3-yl)-3-methylpiperazine-l-carboxylate 191i (1.0 g, 1.0 eq., 2.3 mmol), Pin2B2 (1.46 g, 2.50 eq., 5.75 mmol), Pd2(dba)3 (105 mg, 0.05 eq., 0.125 mmol), X-Phos (93 mg, 0.1 eq., 0.23 mmol), potassium acetate (676 mg, 3.0 eq., 6.9 mmol), and dioxane (50 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90°C for 4 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was washed with 3 : 1 petroleum ether/ethyl acetate (80 mL) to afford 191j as yellow solid (1.0 g, 90%). MS: [M+H]+ 482.

pipeline

http://www.gene.com/medical-professionals/pipeline

Pictrelisib, GDC-0941, RG7321 and GNE0941

Patent ID Date Patent Title
US8921353 2014-12-30 Heteroaryl pyridone and aza-pyridone compounds
US2014378432 2014-12-25 HETEROARYL PYRIDONE AND AZA-PYRIDONE COMPOUNDS
US8716274 2014-05-06 Heteroaryl pyridone and aza-pyridone compounds

 

Patent ID

Title

Submitted Date

Granted Date

US8716274 Heteroaryl pyridone and aza-pyridone compounds
2012-11-02
2014-05-06
US9782405 HETEROARYL PYRIDONE AND AZA-PYRODINE COMPOUNDS
2015-11-17
2016-08-11
US8921353 Heteroaryl pyridone and aza-pyridone compounds
2014-03-13
2014-12-30
US2017247381 DOSAGE FORM COMPOSITIONS COMPRISING AN INHIBITOR OF BRUTON’S TYROSINE KINASE
2017-02-27
US9238655 HETEROARYL PYRIDONE AND AZA-PYRIDONE COMPOUNDS
2014-09-08
2014-12-25

Development of an Efficient Manufacturing Process for Reversible Bruton’s Tyrosine Kinase Inhibitor GDC-0853

Department of Small Molecule Process ChemistryGenentech, Inc.1 DNA Way, South San Francisco, California 94080, United States
Department of Process Chemistry and Catalysis and Department of Drug Substance Scale-up and SupplyF. Hoffmann-La Roche AGGrenzacherstrasse 124, 4070 Basel, Switzerland
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.8b00134
ACS Editors’ Choice – This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. https://pubs.acs.org/doi/10.1021/acs.oprd.8b00134
Abstract Image

Efforts toward the process development of reversible Bruton’s tyrosine kinase (BTK) inhibitor GDC-0853 (1) are described. A practical synthesis of GDC-0853 was accomplished via a key highly regioselective Pd-catalyzed C–N coupling of tricyclic lactam 5 with 2,4-dichloronicotinaldehyde (6) to afford the C–N coupling product 3, a Suzuki–Miyaura cross-coupling of intermediate 3 with boronic ester 4 derived from a Pd-catalyzed borylation of tetracyclic bromide 7, to generate penultimate aldehyde intermediate 2 and subsequent aldehyde reduction and recrystallization. Process development of starting materials 56, and 7 is also discussed.

(S)-2-(3′-(Hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro-[3,4′-bipyridin]-2′-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one (crude GDC-0853, 1)

GDC-0853 (1, 196 kg, 81% yield, >99 A%, Pd < 10 ppm): mp 271 °C (DSC);

FTIR (cm–1, neat) 3430, 3313, 2945, 2865, 1606, 1573;

1H NMR (400 MHz, CDCl3) δ 8.65 (d, J = 2.2 Hz, 1H), 8.48 (d, J = 5.1 Hz, 1H), 7.96 (d, J = 2.7 Hz, 1H), 7.83 (d, J = 2.3 Hz, 2H), 7.36 (d, J = 5.1 Hz, 1H), 7.31 (dd, J = 8.9, 2.8 Hz, 1H), 6.87–6.76 (m, 2H), 5.18–4.98 (m, 1H), 4.77–4.58 (m, 5H), 4.50 (m, 1H), 4.33 (m, 1H), 4.16 (m, 2H), 3.86 (m, 1H), 3.71 (s, 3H), 3.61–3.38 (m, 2H), 3.07 (m, 2H), 2.67–2.39 (m, 7H), 2.20 (dd, J = 10.8, 6.3 Hz, 1H), 1.27 (s, 6H), 0.98 (d, J = 6.3 Hz, 3H);

13C NMR (101 MHz, CDCl3) δ 161.7, 157.6, 154.3, 150.3, 148.4, 141.9, 140.0, 131.4, 131.1, 129.7, 128.8, 127.7, 125.8, 123.9, 117.2, 116.3, 112.4, 111.3, 75.5, 75.5, 59.4, 59.1, 56.3, 52.9, 50.0, 49.2, 48.2, 45.9, 42.7, 40.9, 39.6, 38.5, 30.3, 15.3.

HRMS (ESI+) calcd for C37H45N8O4 ([M + H]+), 665.3564; found, 665.3588.

https://pubs.acs.org/doi/suppl/10.1021/acs.oprd.8b00134/suppl_file/op8b00134_si_001.pdf

/////////////

O=C1N(C)C=C(C2=CC=NC(N3CCN4C(C3=O)=CC5=C4CC(C)(C)C5)=C2CO)C=C1NC(N=C6)=CC=C6N7CCN(C8COC8)C[C@@H]7C

//////GDC 0853, Btk inhibitor, phase 1, Patients with Resistant B-Cell Lymphoma,  Chronic Lymphocytic Leukemia, Bruton tyrosine kinase inhibitor,  GDC-0853,  RG 7845, 1434048-34-6, Fenebrutinib

N1(CCN(CC1C)C2COC2)c3cnc(cc3)NC=4C(N(\C=C(/C=4)c5c(c(ncc5)N6CCn7c(C6=O)cc8CC(Cc78)(C)C)CO)C)=O

CC1CN(CCN1C2=CN=C(C=C2)NC3=CC(=CN(C3=O)C)C4=C(C(=NC=C4)N5CCN6C7=C(CC(C7)(C)C)C=C6C5=O)CO)C8COC8

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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, amcrasto@gmail.com, +91 9323115463 India.

I , Dr A.M.Crasto is writing this blog to share the knowledge/views, after reading Scientific Journals/Articles/News Articles/Wikipedia. My views/comments are based on the results /conclusions by the authors(researchers). I do mention either the link or reference of the article(s) in my blog and hope those interested can read for details. I am briefly summarising the remarks or conclusions of the authors (researchers). If one believe that their intellectual property right /copyright is infringed by any content on this blog, please contact or leave message at below email address amcrasto@gmail.com. It will be removed ASAP

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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