- Development of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge
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The development of the late-phase manufacturing process of the drug candidate ZPL389 and the strategies for the control of impurities are outlined in detail. Selective salt formation at several stages was pivotal to controlling the process impurities. The extensive optimization of the N-methylation of a Boc-protected amine with dimethyl sulfate and of a nucleophilic aromatic substitution without the use of metal catalysts led to a robust, scalable process. The process was demonstrated on a >100 kg scale. Overall, improved drug substance quality, higher yield, and reduction of the process mass intensity were achieved.
- Santandrea, Ernesto,Waldraff, Christine,Gerber, Gilles,Moreau, Ma?l,Beney, Pascal
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- AMINOALKYLPYRIMIDINE DERIVATIVES AS HISTAMINE H4 RECEPTOR ANTAGONISTS
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Aminoalkyipyrimidine derivatives of formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 52
(2011/07/09)
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- 2H-PYRAZOLO [4,3-D]PYRIMIDIN-5-AMINE DERIVATIVES AS H4 HISTAMINE RECEPTOR ANTAGONISTS FOR THE TREATMENT OF ALLERGIC, IMMUNOLOGICAL AND INFLAMMATORY DISEASES
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Pyrazolopyrimidine derivatives of formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 91
(2010/04/30)
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- PIPERIDIN-PYRIMIDINE DERIVATIVES AS ANTAGONISTS OF HISTAMINE H4 RECEPTOR
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Piperidin-pyrimidine derivatives of formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 68
(2010/09/17)
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- FURO[3,2-D]PYRIMIDINE DERIVATIVES
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Furo[3,2-d]pyrimidine derivatives of formula I, wherein the meanings for the various substituents are as defined in the description. These compounds are useful as H4 receptor antagonists.
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Page/Page column 54
(2009/06/27)
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- 2 -AMINOPYRIMIDINE DERIVATIVES AS HISTAMINE H4 ANTAGONISTS
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2-Amino-pyrimidine derivatives of formula I, wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine receptor H4antagonists.
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Page/Page column 101
(2009/07/18)
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- 4-AMINO-PYRIMIDINE DERIVATIVES
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4-Amino-pyrimidine derivatives of Formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 72
(2009/07/25)
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- 2 -AMINO-PYRIMIDINE DERIVATIVES AS HISTAMINE H4 ANTAGONISTS
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2-Aminopyrimidine derivatives of formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 54
(2009/07/03)
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- FURO [3, 2-D] PYRIMIDINE DERIVATIVES AS H4 RECEPTOR ANTAGONISTS
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Furo[3,2-d]pypnnidine derivatives of formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 78
(2009/10/22)
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- Macrocyclic Spiro Pyrimidine Derivatives
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Macrocyclic spiro pyrimidine compounds, compositions comprising such compounds, methods for making the compounds, and methods of treating and preventing the progression of diseases, conditions, and disorders using such compounds and compositions are described herein.
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Page/Page column 77-78
(2009/09/28)
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- SUBSTITUTED PYRIMIDINE DERIVATIVES
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The present application describes substituted pyrimidine compounds of formula (I) wherein X, A1, R1, R2, R3, R4, R5, R6, R7, R8, R9, p, q, r, v,
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Page/Page column 27
(2009/10/31)
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- MACROCYCLIC BENZOFUSED PYRIMIDINE DERIVATIVES
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Macrocyclic benzofused pyrimidine compounds, compositions comprising such compounds, methods for making the compounds, and methods of treating and preventing the progression of diseases, conditions and disorders using such compounds and compositions are described herein.
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Page/Page column 120-121
(2008/12/05)
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- Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: A new class of histamine H4 receptor antagonists with improved druglikeness and in vivo efficacy in pain and inflammation models
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A new structural class of histamine H4 receptor antagonists (6-14) was designed based on rotationally restricted 2,4-diaminopyrimidines. Series compounds showed potent and selective in vitro H4 antagonism across multiple species, goo
- Cowart, Marlon D.,Altenbach, Robert J.,Liu, Huaqing,Hsieh, Gin C.,Drizin, Irene,Milicic, Ivan,Miller, Thomas R.,Witte, David G.,Wishart, Neil,Fix-Stenzel, Shannon R.,McPherson, Michael J.,Adair, Ronald M.,Wetter, Jill M.,Bettencourt, Brian M.,Marsh, Kennan C.,Sullivan, James P.,Honore, Prisca,Esbenshade, Timothy A.,Brioni, Jorge D.
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experimental part
p. 6547 - 6557
(2009/10/09)
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- 2-AMINOPYRIMIDINE DERIVATIVES AS MODULATORS OF THE HISTAMINE H4 RECEPTOR ACTIVITY
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2-Aminopyrimidine derivatives of formula (I), wherein the meanings for the various substituents are as disclosed in the description. These compounds are useful as modulators of the H4 receptor.
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Page/Page column 24
(2008/06/13)
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- MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS AND COMPOSITIONS AND METHODS RELATED THERETO
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Melanin-concentrating hormone (MCH) receptor antagonists are disclosed having utility for the treatment of MCH receptor-based disorders such as obesity. The compounds of this invention have the following structure: including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, X, R1, R2, R3, R4, and R5 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.
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