76471-50-6

Upstream product

• 21906-36-5 1-(4-iodophenyl)-2-propanone 
• 21905-93-1 4-Iod-β-nitro-propenylbenzol 
• 15164-44-0 p-(iodophenyl)carboxaldehyde 
• 477260-03-0 2,2,2-trifluoro-N-[(1R)-2-(4-iodophenyl)-1-methylethyl]acetamide 
• 14383-60-9 (R)-(-)-N-acetyl-α-methylphenylethylamine 
• 133906-31-7 (R)-(-)-N-(trifluoroacetyl)-1-(4-nitrophenyl)-2-aminopropane 
• 133867-98-8 (R)-(+)-N-(trifluoroacetyl)-1-(4-aminophenyl)-2-aminopropane 
• 133795-93-4 (R)-4-Nitroamphetamine 
• 156-34-3 l-amphetamine 
• 82691-32-5 Iofetamine hydrochloride 

Downstream Products

• 643093-80-5 tert-butyl [(2R)-2-(6-chloro-3-pyridinyl)-2-hydroxyethyl][(1R)-2-(4-iodophenyl)-1-methylethyl]carbamate 
• 699015-99-1 (1R)-1-(3-chlorophenyl)-2-{[(1R)-2-(4-iodophenyl)-1-methylethyl]amino}ethanol 

Relevant academic research and scientific papers

N-isopropyl-p-iodoamphetamine hydrochloride is predominantly metabolized by CYP2C19

[123I]N-Isopropyl-p-iodoamphetamine hydrochloride ([ 123I]IMP) is clinically used to evaluate blood flow in the brain on single photon emission-computed tomography. This is a rare radiopharmaceutical that undergoes metabolism. The first step is reported to be [ 123I]p-iodoamphetamine formation. The drug-metabolizing enzyme(s) involved remain(s) unclear. This study examined the roles of human cytochrome P450 (P450) in the metabolism of nonradiolabeled IMP with the use of human liver microsomes (HLM) and recombinant human CYP1A1, -1A2, -1B1, -2A6, -2B6, -2C8, -2C9, -2C19, -2D6, -2E1, -3A4, and -3A5. Disappearance of IMP was examined because p-iodoamphetamine was not available. IMP (0.5 μM) time-dependently disappeared when HLM and NADPH-generating system were added to the reaction mixture. (S)-Mephenytoin (1 mM) inhibited the IMP disappearance by approximately 90%. The disappearance of IMP was predominantly catalyzed by recombinant CYP2C19, with Km and Vmax of 8.6 μM and 9.7 nmol · min-1 · nmol P450-1, respectively. IMP disappearance in CYP2C19-deficient HLM (CYP2C19*2/*2) was approximately 30% of that in the presence of HLM harboring wild-type CYP2C19, indicating that IMP is polymorphically metabolized by CYP2C19. High-performance liquid chromatography of the incubation mixture of IMP and CYP2C19 revealed an unidentified peak. As the area of the IMP peak decreased, the area of this unidentified peak increased in a time-dependent fashion. The peak was also detectable on incubation of IMP with HLM. Mass spectrometry revealed that the molecular weight of a compound in this unidentified peak was the same as that of p-iodoamphetamine. Thus, we demonstrated that IMP was predominantly metabolized by CYP2C19 to form p-iodoamphetamine. Copyright

Discovery of a novel series of biphenyl benzoic acid derivatives as highly potent and selective human β3 adrenergic receptor agonists with good oral bioavailability. Part II

The left-hand side (LHS) and central part of our first generation biphenyl (FGB) series was modified to improve in vitro and in vivo β3-AR potency without loss of oral bioavailability. First, in this study, we focused our efforts on replacement of the 3-chlorophenyl moiety in the LHS of FGB analogues with 3-pyridyl ring analogues to adjust the lipophilicity. Second, we investigated the replacement of the central part of this series and discovered that introduction of a methyl group into the α-position of the phenethylamine moiety greatly enhanced potency keeping good oral availability. Finally, the replacement of the two carbon linker of the central part with an ethoxy-based linker provided improved potency and PK profiles. As a result of these studies, several analogues (i.e., 9h, 9k, 91, 10g, 10m, 10p, 10r, 11b, and 11l) were identified that displayed an excellent balance of very higher human β3-AR potency compared to the FGB compounds, high selectivity, and good pharmacokinetic profiles. Furthermore, these several compounds showed high in vivo efficacy in an overactive bladder (OAB) model. These findings suggest that our selected second generation biphenyl (SGB) series compounds may be attractive new successful therapeutic candidates for the treatment of OAB.

AMINOALCOHOL DERIVATIVES

The present invention relates to a compound formula [I]: wherein Y is bond,--O--(CH2)n--(in which n is 1, 2, 3 or 4), etc., Z is cyano, tetrazolyl, etc., R1 is hydrogen, lower alkyl, etc., R2 is hydrogen or an amino protective group, R3 is hydrogen or lower alkyl, R4 is hydrogen or lower alkyl, R5 and R8 are each independently hydrogen, halogen, hydroxy, lower alkyl, etc., R6 is hydrogen, lower alkyl, etc., R9 is hydrogen or lower alkyl, and i is 1 or 2, or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.

Aminoalcohol derivatives

The present invention relates to a compound formula [I]: wherein R1 is hydrogen or halogen, R2 is hydrogen or an amino protective group, R3 is hydrogen or lower alkyl, X is bond, —CH2— or —O—, and Y is ?in which R4 is lower alkoxycarbonyl, ?in which R5 is carboxy(lower)alkyl, etc., ?in which R6 is hydroxy, etc., and so on, or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.

AMINOALCOHOL DERIVATIVES AND THEIR USE AS BETA-3 ADRENERGIC RECEPTOR AGONISTS

The present invention relates to a compound formula [I] or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.

Binding of Substituted and Conformationally Restricted Derivatives of N-(3-Phenyl-n-propyl)-1-phenyl-2-aminopropane at ?-Receptors

Certain benzomorphans, such as N-allylnormetazocine, are classical "?-opiates" that bind both at ? and phencyclidine (PCP) binding sites with modest affinity.Recently, we identified N-substituted 2-phenylaminoethane as being the primary ?-pharmacophore of

Amines useful as brain imaging agents

Certain radioiodine containing amines useful as brain imaging agents are disclosed. The compounds of the invention are represented by the formula STR1 wherein I is a radioisotope of iodine with I-123 being preferred, R is lower alkyl or halogen, R1 and R2 are the same or different and are selected from the group consisting of hydrogen and lower alkyl, R3 and R4 are the same or different and are selected from the group consisting of hydrogen, alkyl, aryl, substituted aryl, aralkyl, substituted aralkyl and substituted carbamoyl methyl or R3 and R4 taken together with the nitrogen to which they are attached form a 5- or 6-membered ring which may be substituted with one or more lower alkyl groups, x is 0 to 4, y is 0 to 3 and z is 0 or 1 and pharmaceutically acceptable acid addition salts thereof.