Genentech, Inc.

Hoffmann-La Roche Inc.

Other

F. Hoffmann-La Roche Ag

Valo Health, Inc.

Forma Tm, LLC

Array Biopharma Inc.

Sirna Therapeutics, Inc.

Genetech, Inc.

Francis Gosselin

Haiming Zhang

Xiaozhang Zheng

Kenneth W Bair

Peter Scott Dragovich

Hans Iding

Po-Wai Yuen

Stephan Bachmann

Timm R Baumeister

Bingsong Han

Zhongguo Wang

Alexandre Joseph Buckmelter

Jian Lin

Chase C Smith

Bruce D Roth

Michelangelo Scalone

Vasant R Jadhav

Steven L Colletti

Thomas Joseph Tucker

Anthony W Shaw

Reinhard Reents

Ngiap-Kie Lim

Scott J Savage

Dominic J Reynolds

Chong Han

Karl H Clodfelter

Alec Fettes

Qingping Tian

Paroma Chakravarty

Sushant Malhotra

Jeffrey Stults

Beat Wirz

Mark Edward Zak

Srinivasan Babu

Karthik Nagapudi

Keith Lee Spencer

Guiling Zhao

David M Tellers

Pirmin Hidber

Xin Linghu

Roland Meier

Peter J Stengel

Weidong Liu

Stefan Hildbrand

Sagar Raj Shakya

Travis Remarchuk

Paul Nichols

Janet L Gunzner-Toste

Ursula Hoffmann

Yamin Zhang

Yu Yuan

Jie Xu

Andrew McClory

Kyle Bradley Pascual Clagg

Nicholas Andrew White

Theresa Cravillion

Andre Hell

Martin Wunderlich

Michael Dalziel

Peter Steidle

Marie Pepelnjak

Alexander Gmehling

Edward Yost

Danial Beaudry

Herbert Yajima

Sean M Kelly

Zhigang Cheng

Sanjeev Kothari

Haiyun Hou

William Nack

Theresa Humphries

Paul D O'Shea

Cheol Keun Chung

Lauren Elizabeth Sirois

Kyle Clagg

Sarah Robinson

Jacob C Timmerman

Jeff Shen

Ugo Jonathan Orcel

Etienne Trachsel

Filip Petronijevic

Nicholas Wong

Allen Hong

Serena Maria Fantasia

Stefan Koenig

Xiongcai Liu

Daniel Zewge

Pankaj Rege

Paul J Nichols

Sebastian Herold

Andreas Stumpf

Christian Moessner

Zackary D Crane

Yonghui Ge

Johannes Adrian Burkhard

Scott Savage

Keena Green

Christian Jenny

Yingqing Ran

Antonio Giovanni Dipasquale

The present invention relates to pharmaceutical compositions comprising Akt protein kinase inhibitors with therapeutic activity against diseases such as cancer as well as processes for their preparation and their use as medicament.

Pharmaceutical compositions comprising AKT protein kinase inhibitors

The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below:

Compounds and compositions for the inhibition of NAMPT

Provided herein are methods of synthesizing quinazoline compounds comprising at least one atropisomeric center.

Synthesis of quinazoline compounds

Provided herein are methods to synthesize compounds useful in the treatment of cancer where such compounds comprise a quinazolinyl core moiety and at least one stereoisomeric or atropisomeric moiety.

Process for synthesis of quinazoline compounds

A manufacturing process to a bis-mesylate salt 1b of the pan-RAF inhibitor 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide. The process features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access penultimate intermediate 7. The final amide coupling of 7 and 2 was accomplished by a mild and safe protocol employing N,N,N',N′-tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the coupling reagent, to produce a 1:1 adduct of the freebase and THF. The adduct afforded compound 1b with excellent yield, purity, and form stability on a multikilogram production scale after reaction with MsOH and recrystallization. The methods are able to produce a compound having upwards of 95% purity.

Synthesis of a bis-mesylate salt of 4-amino-N-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide and intermediates thereto

Pharmaceutical compositions comprising Akt protein kinase inhibitors

Provided herein are solid forms, salts, and formulations of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol, processes and synthesis thereof, and methods of their use in the treatment of cancer.

Solid forms of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3- yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol and processes for preparing fused tricyclic compounds comprising a substituted phenyl or pyridinyl moiety, including methods of their use

Methods for making an arylomycin ring of formula t or salts or solvates thereof, wherein R, R, R, R, R, R, R, R, R, R, R, Rand Pgare as defined herein.

Process for making arylomycin ring analogs

Methods for preparing the Bruton's Tyrosine Kinase ('BTK') inhibitor compound 2-{3'-hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4&#x2032;]bipyridinyl-2&#x2032;-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one are provided. Methods for preparing tricyclic lactam compounds are also provided.

Process for preparing BTK inhibitors

The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below: 

A process for the manufacture N-(5-((5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide (I) wherein the vicinal amino fluoro substituents are introduced by treating 5 with sodium chloro((4-nitrophenyl)sulfonyl)amide and N-bromosucinimide and unraveling the resulting substituted aziridine (6) with trimethylamine trihydrofluoride to afford 7 which is further processed to afford 1. 

Process for the preparation of a medicament

A method of regio-selectively synthesizing an imidazo-pyrimidine compound of formulae (XXa) or (XXb) comprising a step of coupling a first compound of formula XX-P1a or XX-P1b with a second compound of formula XX-P2  This annulation reaction between &#x3b2;-ethoxy acrylamides and phosphorylated aminoimidazoles to furnish imidazo[1,2-a]pyrimidin-amines relies on steering effects from endocyclic and exocyclic phosphorylated aminoimidazoles. The reaction furnishes either 2-amino or 4-amino constitutional isomers of imidazo[1,2-a]pyrimidines with good yields and ranges of 90:10-99:1 regio-selectivity. The reaction is useful in the synthesis of various tracer molecules used in the study of neurological conditions such as where Rand Rtogether with the imidazole ring atoms to which they are bonded form a phenyl ring and the products are substituted benzimidazopyrimidines. The reaction can be generalized to form imidazo[1,2-a]pyrimidines substituted at either of their 2- and 4-positions by alkoxy or thioalkyl groups.

Regio-selective synthesis of imidazo[1,2-a]pyrimidines

A method of synthesizing comprising a step of making an imidazo-pyrimidine compound by coupling a first compound of formula (II) with a second compound of formula (III)  Followed by a deprotection and tosylation step. The methods are able to produce an isotopically substituted molecule having upwards of 95% purity relative to non-isotopically substituted molecules. The invention further comprises compounds of formula: 

Synthesis of labeled imidazo[1,2-A]pyrimidines

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South San Francisco, CA, United States of America

Francis Gosselin