252002-46-3

Upstream product

• 459-22-3 4-fluorophenylacetonitrile 
• 821-48-7 bis-(2-chloroethyl)amine hydrochloride 
• 644981-87-3 1-(3,4-dimethoxybenzyl)-4-(4-fluorophenyl)-4-cyanopiperidine 
• 192069-85-5 1-benzyl-4-(4-fluorophenyl)piperidine-4-carbonitrile 
• 256951-79-8 4-(4-fluorophenyl)-tert-butoxycarbonylpiperidine-4-carbonitrile 

Downstream Products

• 252002-47-4 1-(3-aminopropyl)-4-(4-fluorophenyl)-piperidine-4-carbonitrile 
• 256951-81-2 1-(3-tert-Butoxycarbonylamino-propyl)-4-(4-fluorophenyl)-4-cyano-piperidine 
• 669068-96-6 1-acetyl-4-(4-fluorophenyl)piperidine-4-carbonitrile 
• 1011484-54-0 cis-4-(4-fluorophenyl)-1-(4-isopropylcyclohexyl)-4-piperidinecarbonitrile 
• 1011484-57-3 cis-1-(4-tert-butylcyclohexyl)-4-(4-fluorophenyl)-4-piperidinecarbonitrile 

Relevant academic research and scientific papers

METALLOENZYME INHIBITOR COMPOUNDS

Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.

PIPERIDINE OR PIPERAZINE LINKED IMIDAZOLE AND TRIAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG

The piperidine or piperazine linked imidazole and triazole derivatives, compositions comprising said compounds, alone or in combination with other drugs, and methods of using the compounds for improving the pharmacokinetics of a drug are provided. The compounds of the invention are useful in human and veterinary medicine for inhibiting CYP3A4 and for improving the pharmacokinetics of a therapeutic compound that is metabolized by CYP3A4.

NAPHTHYL ETHER COMPOUNDS AND THEIR USE

Compounds having the following structure wherein R1, R2, R3, R4, R5, R6, R7 m and n are as defined in the specification, in vivo-hydrolysable precursors thereof, pharmaceutically-acceptable salts thereof, the use in therapy and pharmaceutical compositions and methods of treatment using the same.

NAPHTHAMIDE DERIVATIVES AND THEIR USE

Compounds having the following structure wherein R1, R2, R3, R4, m and n are as defined in the specification, in vivo-hydrolysable precursors thereof, pharmaceutically-acceptable salts thereof, the use in therapy and pharmaceutical compositions and methods of treatment using the same.

PIPERIDINE AMINE COMPOUNDS AND THEIR USE

Compounds having the formula[Chemical formula should be inserted here. Please see paper copy] wherein R1, R2, R3, R6, R7 and Ar are as defined in the specification, in vivo-hydrolysable precursors the

CHEMICAL COMPOUNDS

The present invention relates to cyclic amine derivatives of formula(I) (I)whereinR represents halogen, C1-4 alkyl, cyano, C1-4 alkoxy, trifluoromethyl or trifluoromethoxy;R1 represents hydrogen, halogen, C3-7cycloalkyl, hydroxy, nitro, cyano or C1-4 alkyl optionally substituted by halogen, cyano or C1-4 alkoxy;R2 represents hydrogen or C1-4 alkyl;R3 and R4 independently represent hydrogen, cyano, C1-4 alkyl or R3 together with R4 represents C3-7 cycloalkyl;R5 represents trifluoromethyl, S(O)t C 1-4 alkyl, C1-4 alkyl, C1-4 alkoxy, trifluoromethoxy, halogen or cyano;R6 represents hydrogen or (CH2)rR7;R7 represents hydrogen, C3-7 cycloalkyl, NH(C1-4alkylOC1-4alkoxy), NH(C1-4alkyl), N(C1-4alkyl)2, OC(O)NR9R8, NR8C(O)R9 or C(O)NR9R8;R9 and R8 independently represent hydrogen, C1-4 alkyl or C3-7 cycloalkyl; m represents zero or an integer from 1 to 4;n represents 1 or 2;p is zero or an integer from 1 to 3;q is an integer from 1 to 3;r is an integer from 1 to 4;t is 0, 1 or 2;provided that when m is 0, p is 2, q, r and n represent 1, R1, R2,R3, R4, R5 and R7 are hydrogen and R is chlorine, R5 is not iodine; and pharmaceutically acceptable salts and solvates thereof; process for their preparation and their use in the treatment of conditions mediated by tackykinins and/or by selective inhibition of serotonin reuptake transporter protein.

Alpha 1A adrenergic receptor antagonists

This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

Design and synthesis of novel α(1a) adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety

We have previously described compound 1a as a high-affinity subtype selective α(1a) antagonist. In vitro and in vivo evaluation of compound 1a showed its major metabolite to be a μ-opioid agonist, 4-methoxycarbonyl-4- phenylpiperidine (3). Several dihydropyrimidinone analogues were synthesized with the goal of either minimizing the formation of 3 by modification of the linker or finding alternative piperidine moieties which when cleaved as a consequence of metabolism would not give rise to μ-opioid activity. Modification of the linker gave several compounds with good {1a) binding affinity (K(i) = 300 fold over α(1b) and α(1d)). In vitro analysis in the microsomal assay revealed these modifications did not significantly affect N-dealkylation and the formation of the piperidine 3. The second approach, however, yielded several piperidine replacements for 3, which did not show significant μ-opioid activity. Several of these compounds maintained good affinity at the α(1a) adrenoceptor and selectivity over α(1b) and α(1d). For example, the piperidine fragments of (+)-73 and (+)-83, viz. 4-cyano-4-phenylpiperidine and 4-methyl-4-phenylpiperidine, were essentially inactive at the μ-opioid receptor (IC50 > 30 μM vs 3 μM for 3). Compounds (+)-73 and (+)-83 were subjected to detailed in vitro and in vivo characterization. Both these compounds, in addition to their excellent selectivity (> 880-fold) over α(1b) and α(1d), also showed good selectivity over several other recombinant human G-protein coupled receptors. Compounds (+)-73 and (+)-83 showed good functional potency in isolated human prostate tissues, with K(b)s comparable to their in vitro α(1a) binding data. In addition, compound (+)-73 also exhibited good uroselectivity (DBP K(b)/IUP K(b) > 20-fold) in the in vivo experiments in dogs, similar to 1a.