- Process development and scale-up of a selective α1- adrenoceptor antagonist
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A synthetic route to a potent and selective α-1-adrenergic receptor antagonist has been developed and demonstrated in a pilot plant. The route has been used in two pilot plant campaigns and has produced RO3203546 in 2.3 and 12.0 kg batch sizes. The first pilot plant campaign focused primarily on the end-game of the process with particular emphasis on the development of a method to isolate the active pharmaceutical ingredient (API). The second pilot plant campaign allowed front-end process improvements to be demonstrated. The reiterative process improvements resulted in an economical process with improved throughput and product quality when compared to the original discovery synthesis.
- Connolly, Terrence J.,Matchett, Michael,Sarma, Keshab
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Read Online
- With the biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound and its preparation method and application (by machine translation)
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The invention discloses a has biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound and its preparation method and application, which belongs to the with anti-tumor activity to the technical field of the synthesis of the compounds. The technical scheme of the present invention is to point: has biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound, has the following structure:, wherein R1 For the ethyl carboxylic acid ester, ethylamine methyl, formyl methyl amine, dimethyl amino formyl, pyridine - 3 - methylene amino formyl, piperidine a acyl or anilino formyl, R2 For hydrogen or phenmethyl. The invention also discloses the has biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound of preparation method and the preparation of anti-mammary tumor application of the medicament. The process of preparing the process is simple, easy to control, the target product high yield and good repeatability, prepared with anti-tumor activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compounds are all on breast cancer cell MCF - 7 has definite inhibitory effect. (by machine translation)
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Paragraph 0043-0046
(2017/08/02)
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- Inhibitors of HIV-1 attachment: The discovery and structure-activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore
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6,6-Fused ring systems including tetrahydroisoquinolines and tetrahydropyrido[3,4-d]pyrimidines have been explored as possible replacements for the piperazine benzamide portion of the HIV-1 attachment inhibitor BMS-663068. In initial studies, the tetrahydroisoquinoline compounds demonstrate sub-nanomolar activity in a HIV-1 pseudotype viral infection assay used as the initial screen for inhibitory activity. Analysis of SARs and approaches to optimization for an improved drug-like profile are examined herein.
- Swidorski, Jacob J.,Liu, Zheng,Yin, Zhiwei,Wang, Tao,Carini, David J.,Rahematpura, Sandhya,Zheng, Ming,Johnson, Kim,Zhang, Sharon,Lin, Pin-Fang,Parker, Dawn D.,Li, Wenying,Meanwell, Nicholas A.,Hamann, Lawrence G.,Regueiro-Ren, Alicia
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p. 160 - 167
(2015/12/18)
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- DIKETOPIPERIDINE DERIVATIVES AS HIV ATTACHMENT INHIBITORS
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Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, diketopiperidine derivatives that possess unique antiviral activity are provided. These compounds are useful for the treatment of HIV and AIDS.
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- HETEROBICYCLIC COMPOUNDS USEFUL AS KINASE INHIBITORS
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A compound of Formula (I) and enantiomers, diastereomers and pharmaceutically-acceptable salts thereof. Also disclosed are pharmaceutical compositions containing compounds of Formula I, and methods of treating conditions associated with the activity of p3
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Page/Page column 45
(2008/12/08)
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- NOVEL COMPOUNDS AS P2X7 MODULATORS AND USES THEREOF
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Compounds are disclosed that have a formula represented by the following (I), the compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including
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Page/Page column 42
(2010/11/26)
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- Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds
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The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.
- Murali Dhar,Wrobleski, Stephen T.,Lin, Shuqun,Furch, Joseph A.,Nirschl, David S.,Fan, Yi,Todderud, Gordon,Pitt, Sidney,Doweyko, Arthur M.,Sack, John S.,Mathur, Arvind,McKinnon, Murray,Barrish, Joel C.,Dodd, John H.,Schieven, Gary L.,Leftheris, Katerina
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p. 5019 - 5024
(2008/03/11)
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- TETRAHYDROPYRIDO[3,4-D]PYRIMIDINES AND RELATED ANALOGUES
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Tetrahydropyrido[3,4-d]pyrimidines and related analogues are provided, of the formula (I) in which variables are as described herein, as are methods for their preparation and use. Such compounds may generally be used to modulate ligand binding to histamin
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Page/Page column 40
(2008/06/13)
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- Antagonists to the vanilloid receptor subtype 1 (VR1) and uses thereof
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Compounds having formula (I) or formula (II) or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein A, N, X, Y, R1, R2 and R3 are as defined in the specification. These compounds are particul
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Page/Page column 10; 14
(2008/06/13)
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- Bicycloheteroarylamine compounds as ion channel ligands and uses thereof
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Amine compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.
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- PHENYL-ANILINE SUBSTITUTED BICYCLIC COMPOUNDS USEFUL AS KINASE INHIBITORS
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Compounds having the formula (I), and pharmaceutically acceptable salts, prodrugs, and solvates thereof, are useful as kinase inhibitors, wherein R, R1 , R2, R5, R6a, R6b, J, K, X and Z are as described in the specification.
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Page/Page column 86
(2010/02/11)
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- BICYCLOHETEROARYLAMINE COMPOUNDS AS ION CHANNEL LIGANDS AND USES THEREOF
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Amine compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, includin
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Page/Page column 59-60
(2010/02/12)
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- Quinazolone derivatives as alpha 1A/B adrenergic receptor antagonists
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This invention relates to compounds which are generally alpha-1A/B adrenoceptor antagonists and which are represented by Formula I: wherein Z is —C(O)— or —S(O)2—, X is carbon or nitrogen, Y is carbon, and X-Y considered together are two adjoin
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- Quinoline and quinazoline compounds useful in therapy
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PCT No. PCT/EP96/05609 Sec. 371 Date Jun. 17, 1998 Sec. 102(e) Date Jun. 17, 1998 PCT Filed Dec. 5, 1996 PCT Pub. No. WO97/23462 PCT Pub. Date Jul. 3, 1997The invention provides compounds of formula (I), wherein R1 represents C1-4 alkoxy optionally substituted by one or more fluorine atoms; R2 represents H or C1-6 alkoxy optionally substituted by one or more fluorine atoms; R3 represents one or more groups independently selected from H, halogen, C1-4 alkoxy and CF3; in addition, R2 and one R3 group may together represent -OCH2-, the methylene group being attached to the ortho-position of the pendant phenyl ring; R4 represents a 4-, 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O and S, the ring being optionally fused to a benzene ring or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O and S, the ring system as a whole being optionally substituted; X represents CH or N; and L is absent or represents a cyclic group or an open chain group; and pharmaceutically acceptable salts thereof. The compounds of formula (I) are useful in the treatment of inter alia benign prostatic hyperplasia.
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