- COMPOUNDS OF PHOSPHINANES AND AZAPHOSPHINANES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I) wherein: Ak1 represents an alkyl chain, X represents —(CH2)m—, —CH(R)—, —N(R)—, —CH2—N(R)—, —N(R)—CH2— or —CH2—N(R)—CH2—, m and R are as defined in the description, R1 and R2 each represent H when X represents —(CH2)m—, —CH(R)—, —N(R)—, —CH2—N(R)— or —N(R)—CH2—, or together form a bond when X represents —CH2—N(R)—CH2—, R3 represents NH2, Cy-NH2, Cy-Ak3-NH2 or piperidin-4-yl, Cy and Ak3 are as defined in the description, R4 and R5, which may be identical or different, each represent H or F, their optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in treating conditions requiring a TAFIa inhibitor.
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Paragraph 0314; 0344; 0345
(2018/02/27)
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- Based on 4 - phenyl -6 - (2, 2, 2 - trifluoro -1 - phenyl ethoxy) pyrimidine compound and its application method
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The present invention relates to compounds based on 4-phenyl-6-(2,2,2-trifluoro-1-phenyl ethoxy) pyrimidine and an application method thereof, particularly discloses compounds of formula I and compositions comprising the compounds, and the application method thereof in treatment, prevention and / or management of diseases or disorders.
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Paragraph 0240
(2017/08/25)
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- 1,3,8-TRIAZASPIRO[4,5]DECAN-4-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ORL-1 RECEPTOR MEDIATED DISORDERS
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The present invention is directed to novel 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formulawherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, substance abuse, neuropathic pain, acute pain, migraine, asthma, cough and for improved cognition.
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Paragraph 0133-0136
(2017/02/28)
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- METHODS OF AFFECTING GASTROINTESTINAL TRANSIT AND GASTRIC EMPTYING, AND COMPOUNDS USEFUL THEREIN
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Methods and compounds are disclosed for affecting gastrointestinal motility and gastric emptying, which comprise inhibiting tryptophan hydroxylase (TPH) in patients in need thereof.
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- 4-PHENYL-6-(2,2,2-TRIFLUORO-1-PHENYLETHOXY)PYRIMIDINE-BASED COMPOUNDS AND METHODS OF THEIR USE
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Compounds of formula I are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and/or manage diseases and disorders:
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Page/Page column 20
(2008/12/06)
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- Design and synthesis of 6-fluoro-2-naphthyl derivatives as novel CCR3 antagonists with reduced CYP2D6 inhibition
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In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC50 value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC50 value of 400 nM. In order to reduce its CYP2D6 inhibitory activity, we performed further systematic structural modifications on 1. In particular, we focused on reducing the number of lipophilic moieties in the biphenyl part of 1, using C log D7.4 values as the reference index of lipophilicity. This research led to the identification of N-{(3-exo)-8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-3-(piperidin-1-ylcarbonyl)isonicotinamide 1-oxide (30) which showed comparable CCR3 inhibitory activity (IC50 = 23 nM) with much reduced CYP2D6 inhibitory activity (IC50 = 29,000 nM) compared with 1.
- Sato, Ippei,Morihira, Koichiro,Inami, Hiroshi,Kubota, Hirokazu,Morokata, Tatsuaki,Suzuki, Keiko,Iura, Yosuke,Nitta, Aiko,Imaoka, Takayuki,Takahashi, Toshiya,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-ichi
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p. 8607 - 8618
(2008/12/23)
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- 1,3,8-Triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders
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The present invention is directed to novel 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, substance abuse, neuropathic pain, acute pain, migraine, asthma, cough and for improved cognition.
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- Preparation of 2- and 5-aryl substituted thiazoles via palladium-catalyzed Negishi cross-coupling
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2-Aryl substituted thiazoles 3a-k were prepared by oxidative insertion of zinc into 2-bromothiazole (1) followed by palladium(0)-catalyzed Negishi cross-coupling in a one-pot procedure. 5-Aryl substituted thiazoles 6a-i were prepared by regioselective C-5 lithiation of 2-(trimethylsilyl)thiazole (4) followed by transmetalation with zinc chloride and palladium(0)-catalyzed Negishi cross-coupling in a one-pot procedure. The synthetic sequences were combined to give 2,5-diaryl substituted thiazoles 8a,b and 10 via stepwise C-2 and C-5 arylation and vice versa.
- Jensen,Skj?rb?k,Veds?
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p. 128 - 134
(2007/10/03)
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