- FUMAGILLOL COMPOUNDS AND METHODS OF MAKING AND USING SAME
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Disclosed herein, in part, are fumagillol compounds and methods of use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making fumagillol compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
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Paragraph 00239
(2018/03/06)
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- Urea Derivatives of 2-Aryl-benzothiazol-5-amines: A New Class of Potential Drugs for Human African Trypanosomiasis
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A previous publication from this lab (Patrick, et al. Bioorg. Med. Chem. 2016, 24, 2451-2465) explored the antitrypanosomal activities of novel derivatives of 2-(2-benzamido)ethyl-4-phenylthiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of human African trypanosomiasis. While a number of these compounds, particularly the urea analogues, were quite potent, these molecules as a whole exhibited poor metabolic stability. The present work describes the synthesis of 65 new analogues arising from medicinal chemistry optimization at different sites on the molecule. The most promising compounds were the urea derivatives of 2-aryl-benzothiazol-5-amines. One such analogue, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole (57) was chosen for in vivo efficacy studies based upon in vitro activity, metabolic stability, and brain penetration. This compound attained 5/5 cures in murine models of both early and late stage human African trypanosomiasis, representing a new lead for the development of drugs to combat this neglected disease.
- Patrick, Donald A.,Gillespie, J. Robert,McQueen, Joshua,Hulverson, Matthew A.,Ranade, Ranae M.,Creason, Sharon A.,Herbst, Zackary M.,Gelb, Michael H.,Buckner, Frederick S.,Tidwell, Richard R.
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supporting information
p. 957 - 971
(2017/02/19)
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- N-Acyl-N'-(pyridin-2-yl) Ureas and Analogs Exhibiting Anti-Cancer and Anti-Proliferative Activities
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Described are compounds of Formula I which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-1R), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c-FMS, c-KIT, or PDGFR kinases.
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Paragraph 0363
(2014/09/30)
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- PROCESS FOR PREPARING ALISKIREN AND ITS INTERMEDIATES
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The present application relates to a process for the preparation of aliskiren and its pharmaceutically acceptable salts. In particular, the present application relates to a process for the preparation of intermediates for aliskiren, and their conversion to aliskiren or its salts.
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Page/Page column 29-30
(2012/03/09)
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- PROCESS FOR THE PREPARATION OF (2S,4S,5S,7S)-N-(2-CARBAMYL-2- METHYLPROPYL)-5-AMINO-4-HYDROXY-2,7-DIISOPROPYL-8-[4-METHOXY-3-(3- METHOXYPROPOXY)PHENYL]-OCTANAMIDE HEMIFUMARATE AND ITS INTERMEDIATES THEREOF
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The present invention relates to a process for the preparation of (2S,4S,5S,7S)-N-(2- Carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxy propoxy )phenyl]-octanamide compound of formula- 1 and its pharmaceutically acceptable salts thereof. Further, relates to the processes for the preparation of (R)-4-(2-(halomethyl)-3- methylbutyl)-l-methoxy-2-(3-methoxypropoxy) benzene and (R)-2-(4-methoxy-3-(3-methoxy propoxy) benzyl)-3-methyIbutan-l-ol useful intermediates in the synthesis of compound of formula- 1.
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Page/Page column 64
(2011/12/14)
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- A PROCESS FOR DIMETHYLATION OF ACTIVE METHYLENE GROUPS
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The present invention discloses a process for dimethylation of active methylene groups. Specifically, the invention discloses aprocess for preparing3-amino-2,2- dimethylpropanamide. Compounds produced by the present dimethylation process such as 3-amino-2,2-dimethylpropanamide can be used as intermediates in the route of synthesis of therapeutic, prophylactic or diagnostic agent, for example aliskiren or cryptophycin. Particularly, the invention relates to embodiments further extending to processesfor preparing pharmaceutical dosage form comprising said therapeutic, prophylactic or diagnostic agents. More specifically, the invention relates to the use of compounds produced by the present dimethylation process for the manufacture of therapeutic, prophylactic or diagnostic agents or for the manufacture of pharmaceutical dosage forms comprising said therapeutic, prophylactic or diagnostic agents. The processes according to the present invention can be beneficially applied for the synthesis of various active pharmaceutical ingredients, such as aliskiren or crypthophycin.
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Page/Page column 29
(2010/11/03)
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- Practical synthesis of an orally active renin inhibitor aliskiren
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A convergent synthesis of aliskiren was accomplished via the use of Segment AB as the key intermediate, which was prepared via the coupling of the Grignard reagent derived from Segment B with Segment A, followed by subsequent oxidative lactonization.
- Dong, Hua,Zhang, Zhi-Liu,Huang, Jia-Hui,Ma, Rujian,Chen, Shu-Hui,Li, Ge
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p. 6337 - 6340
(2007/10/03)
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- A NOVEL REACTION OF α,γ-DINITRO COMPOUNDS. TRANSFORMATION OF METHYL 4,6-DINITRO-5,5-DIMETHYLHEXANOATE TO 2,2-DIMETHYL-3-OXIMINOADIPATE AND SUBSEQUENT CYCLIZATION TO 3-(4,4-DIMETHYL-5-KETO-3-ISOXAZOLE)PROPIONIC ACID
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Methyl 4,6-dinitro-5,5-dimethylhexanoate (2) is converted by catalytic quantities of sodium methoxide and ammonia to dimethyl 2,2-dimethyl-3-oximinoadipate (10) and 2,2-dimethyl-3-oximinoadipamide (11), respectively.On treatment with dilute acid, compounds 10 and 11 are readily cyclized to 3-(4,4-dimethyl-5-keto-3-isoxazole)propionic acid (3).Compound 3 is also obtained directly from compound 2 on treatment with base and subsequent acidification.
- Feuer, Henry,Halasa, Adel F.
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p. 1281 - 1288
(2007/10/02)
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