- A New Synthesis of Coprine and O-Ethylcoprine
-
Coprine (1), a toxine of the mushroom Coprinus atramentarius, was synthesized starting from the 2-amino- and 1-carboxy-protected L-glutamic acids 4 and 12.Compound 4 was first decarboxylated by radical chain reaction to bromide 5 which underwent ring closure to cyclopropanecarboxylate 6 on treatment with NaH (Scheme 1).Subsequent oxidative electrolysis of 7 to form tert-butyl N-(1-ethoxycyclopropyl)carbamate (8) and acidic hydrolysis yielded the 1-aminocyclopropanol hydrochloride (9).Selective cleavage of the amino-protecting group of 8(-> 10 or 11), coupling of the corresponding amine 13 with L-glutamic acid 12, and acidic hydrolysis of the resulting L-glutamine derivative 17 yielded O-ethylcoprine (3) and coprine (1).
- Kienzler, Thomas,Strazewski, Peter,Tamm, Christoph
-
-
Read Online
- AZETIDIN-3-YLMETHANOL DERIVATIVES AS CCR6 RECEPTOR MODULATORS
-
The present invention relates to compounds of Formula (I), their synthesis and use as CCR6 receptor modulators for the treatment or prevention of various diseases, conditions or disorders.
- -
-
Page/Page column 169; 170
(2021/11/06)
-
- ANTIVIRAL PYRIDOPYRAZINEDIONE COMPOUNDS
-
The invention provides compounds of Formula (I) as described herein, along with pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and methods to use these compounds, salts and compositions for treating viral infections, particularly infections caused by herpesviruses.
- -
-
Paragraph 0580-0581
(2020/04/09)
-
- Hepatitis C Virus Inhibitors
-
The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.
- -
-
Paragraph 1751-1752
(2015/02/25)
-
- COMBINATIONS OF HEPATITIS C VIRUS INHIBITORS
-
The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.
- -
-
Page/Page column 587
(2015/02/02)
-
- DIBENZOTHIOPHENE DERIVATIVES AS DNA- PK INHIBITORS
-
Compound formula I: wherein: X1 and X2 may be either (a) C and O, (b) N and N, or (c) C and NH, where the dotted bonds represents a double bond in the appropriate location; R1 and R2 are independently selected from hydrogen, an optionally substituted C1-7 alkyl group, an optionally substituted C3-20 heterocyclyl group, or an optionally substituted C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; RN1 is selected from hydrogen and an optionally substituted C1-4 alkyl group; RC1 is selected from an optionally substituted C1-7 alkyl group, an optionally substituted C3-20 heterocyclyl group, or an optionally substituted C5-20 aryl group; or RN1 and RC1 may together form an optionally substituted C2-4 alkylene group.
- -
-
Page/Page column 61-62
(2010/12/26)
-
- Toward the back-up of Boceprevir (SCH 503034): Discovery of new extended P4-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease with improved potency and pharmacokinetic profiles
-
Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P4 pocket and optimization of the P1′ capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P4-capped inhibitors were also found to have improved PK profile.
- Bogen, Stéphane L.,Pan, Weidong,Ruan, Sumei,Nair, Latha G.,Arasappan, Ashok,Bennett, Frank,Chen, Kevin X.,Jao, Edwin,Venkatraman, Srikanth,Vibulbhan, Bancha,Liu, Rong,Cheng, Kuo-Chi,Guo, Zhuyan,Tong, Xiao,Saksena, Anil K.,Girijavallabhan, Viyyoor,Njoroge, F. George
-
scheme or table
p. 3679 - 3688
(2010/04/05)
-
- Cyclopropanecarboxylic acid esters as potential prodrugs with enhanced hydrolytic stability
-
Esters of cyclopropanecarboxylic acid demonstrate a substantial increase in stability under both acid- and base-catalyzed hydrolytic conditions. Comparison of the stability of valacyclovir 13 with the cyclopropane analogue 14 shows that at 40 °C and pH 6 the half-life of 14 is >300 h while the value for 13 is 69.7 h. CBS-QB3 calculations on isodesmic reactions for transfer of groups from an alkane to an ester show that a cyclopropyl group provides hyperconjugative stabilization.
- Bender, David M.,Peterson, Jeffrey A.,McCarthy, James R.,Gunaydin, Hakan,Takano, Yu,Houk
-
p. 509 - 511
(2008/09/19)
-
- Cyclic dipeptides and azetidinone compounds and their use in treating CNS injury and neurodegenerative disorders
-
The present invention provides 4-substituted-2-azetidinone compounds, bicyclic 2-5-diketopiperazine compounds, and pharmaceutical compositions thereof that are potent, safe and effective neuroprotective agents. Due to their strong central nervous system (CNS) activity, the compounds can be used to enhance memory and to treat a variety of neurological disorders. The compounds are particularly useful for treating neurological disorders caused by, or associated with, CNS trauma.
- -
-
Page/Page column 50
(2010/11/26)
-