- New cyclooxygenase-2/5-lipoxygenase inhibitors. 3. 7-tert-Butyl-2,3- dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: Variations at the 5 position
-
We report an expansion of the scope of our initial discovery that 5- keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) are antiinflammatory and analgesic agents. Several other functional groups have been introduced at the 5 position: amides, amidines, ureas, guanidines, amines, heterocycles, heteroaromatics, and heteroaryl ethenyl substituents in the 5 position all provide active compounds. These compounds are dual cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitors. They inhibit both COX-1 and COX-2 with up to 33-fold selectivity for COX-2.
- Janusz, John M.,Young, Patricia A.,Ridgeway, James M.,Scherz, Michael W.,Enzweiler, Kevin,Wu, Laurence I.,Gan, Lixian,Chen, Julian,Kellstein, David E.,Green, Shelley A.,Tulich, Jennifer L.,Rosario-Jansen, Theresa,Magrisso, I. Jack,Wehmeyer, Kenneth R.,Kuhlenbeck, Deborah L.,Eichhold, Thomas H.,Dobson, Roy L. M.
-
-
Read Online
- Piperazine derivatives and their use as therapeutic agents
-
Compounds for treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the compounds are of formula (I): where x y, W, V, R 2 , R 3 , R 4 , R 5 , R 6 , R 6a , R 7 , R 7a , R 8 , R 8a , R 9 and R 9a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
- -
-
Paragraph 0102
(2016/03/19)
-
- 2-process for the preparation of cyclopropyl-ethylamine
-
The invention discloses a preparation method of 2-cyclopropyl ethylamine. The method includes the steps of A, compound 1 and nitromethane react under the action of alkali to obtain compound 2; B, the compound 2 is dehydrated under the action of dehydration reagent to obtain compound 3; C, the compound 3 reacts in solvent under the action of reducing agent to obtain compound 4; D, the compound 4 reacts under the action of reduction hydrogenation catalyst to obtain compound 5, namely the 2-cyclopropyl ethylamine. The preparation method has the advantages that operation conditions can be simplified, cost can be lowered, and easiness in large batch production is achieved. The synthesizing route is showed as follows.
- -
-
Paragraph 0044-0046
(2017/01/09)
-
- AMIDE DERIVATIVES AS LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS
-
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, formula (I) wherein R1. X, m. R2, Y, R3, Z, n, R4. A and B are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
- -
-
Page/Page column 59-60
(2015/03/13)
-
- NOVEL COMPOUNDS
-
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, X, m, R2, Y, R3, Z, n, R4, A and B are as defined in the specification, processes for their prep
- -
-
Page/Page column 19
(2015/03/04)
-
- PURINE DERIVATIVES AS IMMUNOMODULATORS
-
The present invention includes novel compounds useful in the treatment of various disorders in particular infectious diseases, cancer, and allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, and as vaccine adjuvants
- -
-
Page/Page column 105
(2008/12/08)
-
- HETEROCYCLIC DERIVATIVES AND THEIR USE AS STEAROYL-COA DESATURASE INHIBITORS
-
Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I) where x, y, J, K, W, V, R3, R4,
- -
-
Page/Page column 42
(2008/06/13)
-
- HETEROCYCLIC DERIVATIVES AND THEIR USE AS MEDIATORS OF STEAROYL-COA DESATURASE
-
Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): Formula (I) where x, y, G, J, L, M, V, W, R2, R3, R4, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
- -
-
Page/Page column 48-49
(2010/10/20)
-
- Importance of the lipophilic group in carbamates having histamine H3- receptor antagonist activity
-
In order to evaluate changes in the lipophilic part of designed carbamates concerning their potential histamine H3-receptor antagonist properties a new series of O-[3-(1H-imidazol-4-yl)propanol]carbamates was derived containing N-mono- or dialkenyl, alkynyl, cycloalkyl, or double- branched alkyl substituents. The compounds were tested in vitro for their H3-receptor antagonist activity on synaptosomes of rat cerebral cortex and shared moderate to high antagonist activity in vitro. In this series 3-(1H- imidazol-4-yl)propyl N-(4-pentenyl)carbamate (4) was the most potent compound in vitro (K(i) = 6.3 nM). H3-receptor antagonist activity in the central nervous system (CNS) was detected for most compounds in the in vivo H3- receptor assay based upon measurement of brain N(τ)-methylhistamine levels after p.o. administration to mice. The most effective carbamate in vivo, 3- (1H-imidazol-4-yl)propyl N-(allyl)carbamate (3), showed higher CNS potency (ED50 = 0.48 mg/kg p.o.) than the reference antagonist thioperamide. For some novel carbamates their histamine H1- and H2-receptor activities were determined on isolated organs of guinea-pig thereby demonstrating their high H3-receptor selectivity.
- Kiec-Kononowicz,Wiecek,Sasse,Ligneau,Elz,Ganellin,Schwartz,Stark,Schunack
-
p. 349 - 355
(2007/10/03)
-
- PYRAZINONE THROMBIN INHIBITORS
-
Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: STR1 for example: STR2
- -
-
-