- PIPERAZINONE-SUBSTITUTED TETRAHYDRO-CARBOLINE MCH-1 ANTAGONISTS, METHODS OF MAKING, AND USES THEREOF
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The present invention relates to piperazinone-substituted tetrahydro-carboline derivatives of formula (I): having the substituents as described herein which are melanin-concentrating hormone (MCH-1) receptor antagonists. The present invention also relates
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Page/Page column 19
(2012/06/30)
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- AZINONE-SUBSTITUTED AZEPINO[b]INDOLE AND PYRIDO-PYRROLO-AZEPINE MCH-1 ANTAGONISTS, METHODS OF MAKING, AND USE THEREOF
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Novel MCH-1 receptor antagonists are disclosed. These compounds are used in the treatment of various disorders, including obesity, anxiety, depression, non-alcoholic fatty liver disease, and psychiatric disorders. Methods of making these compounds are als
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Page/Page column 82
(2011/01/12)
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- New 1-(heterocyclylalkyl)-4-(propionanilido)-4-piperidinyl methyl ester and methylene methyl ether analgesics
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A series of new 1-(heterocyclyalkyl)-4-(propionanilido)-4-piperidinyl methyl esters and methylene methyl ethers have been synthesized and pharmacologically evaluated. In the mouse hot-plate test, the majority of compounds exhibited an analgesia (ED50 1 mg/kg) superior to that of morphine. These studies revealed a pharmacological accommodation for many more structurally diverse and far bulkier aromatic ring systems than the corresponding components of the arylethyl groups of the prototypic methyl ester (carfentanil, 2) and methylene methyl ether (sufentanil, 3 and alfentanil, 4) 4-propionanilido analgesics. Compound 9A (methyl 1-[2-(1H-pyrazol-1-yl)-ethyl]-4-[(1-oxopropyl) phenylamino]-4-piperidinecarboxylate), which exhibited appreciable μ-opioid receptor affinity, was a more potent and short-acting analgesic, than alfentanil with less respiratory depression in the rat. On the other hand, the phthalimides 57A and 57B, which exhibited negligible affinity for opioid receptors associated with the mediation of nociceptive transmission (i.e., μ-, κ-, and δ-subtypes), displayed analgesic efficacy in all antinociception tests. In addition, while 57B, compared to clinical opioids, showed a superior recovery of motor coordination after regaining of righting reflex from full anesthetic doses in the rat rotorod test, 57A showed significantly less depression of cardiovascular function at supraanalgesic doses in the isoflurane-anesthetized rat.
- Bagley,Thomas,Rudo,Spencer,Doorley,Ossipov,Jerussi,Benvenga,Spaulding
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p. 827 - 841
(2007/10/02)
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