- A high-yield route to synthesize the P-glycoprotein radioligand [ 11C]N-desmethyl-loperamide and its parent radioligand [ 11C]loperamide
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N-Desmethyl-loperamide and loperamide were synthesized from α,α-diphenyl-γ-butyrolactone and 4-(4-chlorophenyl)-4- hydroxypiperidine in five and four steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2- diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21-57% overall yield. [11C]N-Desmethyl-loperamide and [ 11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.
- Wang, Min,Gao, Mingzhang,Zheng, Qi-Huang
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p. 5259 - 5263
(2013/09/23)
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- 4-OXADIAZOLYL-PIPERIDINE COMPOUNDS AND USE THEREOF
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4-Oxadiazolyl-piperidine compounds of formula (I) and (II), their compositions and use for the treatment of pain and diarrhoea.
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Page/Page column 88-89
(2008/06/13)
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- METHODS FOR MAKING 4-TETRAZOLYL-4-PHENYLPIPERIDINE COMPOUNDS
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Methods, composition, and intermediates are disclosed that are useful for making 4-Tetrazolyl-4-phenylpiperidine Compounds according to Formula (I), where Ar1 is -C3-C8 cycloalkyl, phenyl, naphthyl, anthryl, phenanthryl or -(5-7-membered) heteroaryl, each being unsubstituted or substituted with one or more R2 groups; Ar2 is phenyl, naphthyl, anthryl, phenanthryl or -(5-7-membered) heteroaryl, each being unsubstituted or substituted with one or more R2 groups; Z1 and Z2 are each independently a -(C1-C4 alkyl) group; R1 is -(CH2)nC(O)N(R3)(R4) where R3 and R4 are each independently H or -(C1-C4 alkyl); R2 is halogen, -C1-C3 alkyl, -O-(C1-C3 alkyl), -NH(C1-C3 alkyl) or -N(C1-C3 alkyl)2; n is an integer ranging from 1 to 4; m is an integer ranging from 0 to 4; and, in certain embodiments, the phenyl moiety attached to the 4-position of the piperidine ring of a compound according to Formula (I) can be optionally substituted with one or mor R2 groups.
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Page/Page column 70; 112
(2008/06/13)
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- Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor
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Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series. Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series.
- Chen, Zhengming,Davies, Ellen,Miller, Wendy S.,Shan, Shen,Valenzano, Kenneth J.,Kyle, Donald J.
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p. 5275 - 5279
(2007/10/03)
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- 2,2-DIPHENYLBUTANAMIDE DERIVATIVES AND MEDICINES CONTAINING THE SAME
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2,2-Diphenylbutanamide derivatives represented by the following formula (1): [wherein A represents -(CH2)n- (n is 1 or 2) or a methine (CH) group; when A is -CH2-, B represents a methine group or a nitrogen atom, with A and B forming a single bond; when A is -(CH2)2-, B represents a nitrogen atom, with A and B forming a single bond; when A is a methine group, B represents a quaternary carbon atom, with A and B forming a double bond; each of R1 and R2, which are identical to or different from each other, represents a hydrogen atom, a lower alkyl group, or a cycloalkyl group, or R1 and R2 may form a heterocyclic ring together with the adjacent nitrogen atom; and Ar represents an optionally substituted phenyl group, bicyclic aromatic ring, monocyclic heterocyclic ring, bicyclic heterocyclic ring, or fluorene group]; or salts of the derivatives. The derivatives or salts thereof exhibit excellent μ-opioid agonist activity and analgesic activity against neuropathic pain, and are useful as medicines such as peripheral analgesic drugs and neuropathic pain relieving drugs.
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- Peripherally active anti-hyperalgesic opiates
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Compositions and methods using the compositions for treatment of peripheral hyperalgesia are provided. The compositions contain an anti-hyperalgesia effective amount of one or more compounds that directly or indirectly interact with peripheral opiate receptors, but that do not, upon topical or local administration, elicit substantial central nervous system effects. The anti-diarrheal compound 4-(p-chlorophenyl)-4-hydroxy-N-N-dimethyl-α,α-diphenyl-1-piperidinebutyramide hydrochloride is preferred for use in the compositions and methods.
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- Triazaspiro compounds, particularly 8-(3,3-diphenylpropyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane derivatives, with opioid receptor stimulating activity, useful for treating or preventing pain.
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Triazaspiro Compounds, compositions comprising a Triazaspiro Compound, methods for treating or preventing pain in an animal comprising administering to an animal in need thereof an effective amount of a Triazaspiro Compound and methods for stimulating opioid-receptor function in a cell comprising contacting a cell capable of expressing an opioid receptor with an effective amount of a Triazaspiro Compound are disclosed.
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- 4-hydroxy-4-phenylpiperidine derivatives and pharmaceuticals containing the same
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Described is a 4-hydroxy-4-phenylpiperidine derivative represented by the following formula (1): [wherein, R1and R2are the same or different and each independently represents a hydrogen atom, a lower alkyl, or the like, R3represents a hydrogen atom or a group —(CR4R5)n—Y (in which, R4and R5each represents a hydrogen atom or a lower alkyl group, Y represents a group —COOR6, —CONR7R8, —OR9or —OCOR10(in which R6, R9and R10each independently represents a hydrogen atom, a lower alkyl group, or the like, R7and R8are the same or different and each independently represents a hydrogen atom, a lower alkyl group, or the like), and n stands for 1 to 6)], or salt thereof. The compound exhibits excellent peripheral analgesic action.
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Referential example 1
(2010/01/31)
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- PERIPHERALLY ACTIVE ANTI-HYPERALGESIC OPIATES
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Compositions and methods using the compositions for treatment of peripheral hyperalgesia are provided. The compositions contain an anti-hyperalgesia effective amount of one or more compounds that directly or indirectly interact with peripheral opiate receptors, but that do not, upon topical or local administration, elicit substantial central nervous system effects. The anti-diarrheal compound 4-(p-chlorophenyl)-4-hydroxy-N-N-dimethyl-α,α-diphenyl-1-piperidinebutyramide hydrochloride is preferred for use in the compositions and methods.
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