Matthew A Zajac

US Patent:

8076475, Dec 13, 2011

Filed:

Mar 6, 2009

Appl. No.:

12/921199

Inventors:

Matthew Allen Zajac - King of Prussia PA, US

Assignee:

GlaxoSmithKline LLC - Philadelphia PA

International Classification:

C07D 401/00

US Classification:

540523

Abstract:

The present invention generally relates to a novel process for preparing vitronectin receptor antagonist compounds having a benzodiazepinyl core structure. This invention relates to the preparation of pharmaceutically active compounds which inhibit the vitronectin receptor and are useful for treatment of inflammation, cancer and cardiovascular disorders, such as atherosclerosis and restenosis, and diseases wherein bone resorption is a factor, such as osteoporosis. In particular, the present invention relates to a novel process for preparing ()-3-oxo-8-{[3-(pyridin-2-ylamino)propyl]oxy}-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetic acid, (R)-3-oxo-8-{[3-(pyridin-2-ylamino)propyl]oxy}-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetic acid and (S)-3-oxo-8-{[3-(pyridin-2-ylamino)propyl]oxy}-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetic acid or a pharmaceutically acceptable salt thereof.

US Patent:

20090143581, Jun 4, 2009

Filed:

Mar 17, 2006

Appl. No.:

11/908901

Inventors:

Andrew G. Myers - Boston MA, US
Seth B. Herzon - Cambridge MA, US
Jeremy Earle Wulff - Victoria, CA
Romain Siegrist - Somerville MA, US
Jakub Svenda - Cambridge MA, US
Matthew Alan Zajac - Douglassville PA, US

Assignee:

PRESIDENT AND FELLOWS OF HARVARD COLLEGE - Cambridge MA

International Classification:

C07D 471/22
C07C 45/61
C07D 209/56
C07D 491/052

US Classification:

544341, 544338, 568361, 548439, 548421

Abstract:

The syntheses of the natural products, avrainvillamide and stephacidin B, are provided. The α,β-unsaturated nitrone functionality of avrainvillamide and its 3-alkylidene-3H-indole 1-oxide core is shown to covalently and reversibly bond to heteroatom-based nucleophiles. This capability may allow these molecules to bind active site nucleophiles and may provide the basis for designing potent and selective enzyme inhibitors. Both avrainvillamide and its dimer stephacidin B have been reported to exhibit antiproliferative activity, and avrainvillamide has been reported to exhibit antimicrobial activity against multi-drug resistant bacteria. Avrainvillamide has been found to target cytoskeleton-linking membrane protein (CLIMP-63) thereby preventing cells from undergoing mitosis. The invention provides syntheses of these natural products as well as analogs of these natural products and their functional cores. The compounds of the invention may be used in the treatment of diseases such as cancer, autoimmune diseases, and bacterial infection.

US Patent:

20110166170, Jul 7, 2011

Filed:

Oct 27, 2010

Appl. No.:

12/913091

Inventors:

Andrew G. Myers - Boston MA, US
Seth B. Herzon - New Haven CT, US
Jeremy Earle Wulff - Victoria, CA
Romain Siegrist - Allschwil, CH
Jakub Svenda - Cambridge MA, US
Matthew Allen Zajac - Douglassville PA, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

A61K 31/437
C07D 487/04
C07D 471/22
C07D 209/56
C07D 209/82
A61K 31/407
A61K 31/403
A61P 35/00

US Classification:

514279, 548421, 546 40, 548418, 548440, 514410, 514411

Abstract:

The syntheses of the natural products, avrainvillamide and stephacidin B, are provided. The α,β-unsaturated nitrone functionality of avrainvillamide and its 3-alkylidene-3H-indole 1-oxide core is shown to covalently and reversibly bond to heteroatom-based nucleophiles. This capability may allow these molecules to bind active site nucleophiles and may provide the basis for designing potent and selective enzyme inhibitors. Both avrainvillamide and its dimer stephacidin B have been reported to exhibit antiproliferative activity, and avrainvillamide has been reported to exhibit antimicrobial activity against multi-drug resistant bacteria. Avrainvillamide has been found to target cytoskeleton-linking membrane protein (CLIMP-63) thereby preventing cells from undergoing mitosis. The invention provides syntheses of these natural products as well as analogs of these natural products and their functional cores. The compounds of the invention may be used in the treatment of diseases such as cancer, autoimmune diseases, and bacterial infection.

US Patent:

20120226053, Sep 6, 2012

Filed:

Sep 1, 2010

Appl. No.:

13/393174

Inventors:

Matthew Allen Zajac - King of Prussia PA, US

International Classification:

C07D 207/09

US Classification:

548537

Abstract:

The present application provides a process for the preparation of α-carboxamide pyrrolidine derivatives of formula (I), wherein Rand Rare independently hydrogen, Calkyl or CcycloalkylCalkyl; or such Rand R, together with the nitrogen to which they are attached, may form an unsubstituted 3-, 4-, 5- or 6-membered saturated ring; X is carbon or nitrogen; n is 0, 1 or 2, wherein when present each Ris independently selected from the list consisting of Calkyl, halogen, cyano, haloCalkyl, hydroxy, Calkoxy and Chaloalkoxy; either Ror Ris —O—R, —OCHRR,—NCHRor —(CH)Rwherein the other Ror Ris hydrogen or R; and wherein Ris a phenyl ring or wherein the phenyl ring is optionally substituted by one or more groups independently selected from the list consisting of Calkyl, halogen, cyano, haloCalkyl, hydroxy, Calkoxy and Chaloalkoxy; and Ris hydrogen or Calkyl.

US Patent:

20130035501, Feb 7, 2013

Filed:

Apr 6, 2011

Appl. No.:

13/639594

Inventors:

Jose J. Conde - King of Prussia PA, US
John Anthony Kowalski - King of Prussia PA, US
Matthew Allen Zajac - King of Prussia PA, US

Assignee:

GLAXOSMITHKLINE LLC - Philadelphia PA

International Classification:

C07F 5/04

US Classification:

558288

Abstract:

The present invention is a process comprising contacting a compound of formula 6:

US Patent:

20160168168, Jun 16, 2016

Filed:

Dec 15, 2015

Appl. No.:

14/969467

Inventors:

- Brentford, GB
John Anthony KOWALSKI - King of Prussia PA, US
Matthew Allen ZAJAC - King of Prussia PA, US

International Classification:

C07F 5/02

Abstract:

The present invention is a process comprising contacting a compound of formula 6:or a pharmaceutically acceptable salt thereof;with a deprotecting reagent to form a compound of formula A:or a pharmaceutically acceptable salt thereof;where R is H or OR; Rand each Rare protecting groups; R is H or OH, and n is 0, 1, 2, 3, 4, or 5.