312937-01-2

Upstream product

• 383-63-1 ethyl trifluoroacetate, 
• 51-45-6 histamine 
• 76-83-5 trityl chloride 
• 56-92-8 histamine dichloride 
• 50580-77-3 2,2,2-trifluoro-N-[2-(1H-imidazol-4-yl)ethyl]acetamide 

Downstream Products

• 620972-22-7 α-N-trifluoroacetyl-3-benzylhistamine 
• 340179-89-7 (1-trityl-1H-imidazol-4-yl)methylamine 
• 476494-04-9 1-[7-((Methanesulfonyl)oxy)naphthyl]-4-[2-(1-triphenylmethyl-4-imidazolyl)-ethyl]-2-piperazinone 
• 476494-03-8 methanesulfonic acid 8-{2-[2-(1-trityl-1H-imidazol-4-yl)-ethylamino]-acetylamino}-naphthalen-2-yl ester 
• 254108-76-4 methanesulfonic acid 8-(4-{2-[3-(4-bromo-3-fluoro-benzyl)-3H-imidazol-4-yl]-ethyl}-2-oxo-piperazin-1-yl)-naphthalen-2-yl ester 
• 312937-07-8 1-(3-chloro-phenyl)-4-[2-(1-trityl-1H-imidazol-4-yl)-ethyl]-piperazin-2-one 
• 312937-03-4 N-(3-chloro-phenyl)-2-[2-(1-trityl-1H-imidazol-4-yl)-ethylamino]-acetamide 
• 620972-31-8 N-[2-(3-benzyl-2-cyclopentyl-3H-imidazol-4-yl)-ethyl]-2,2,2-trifluoro-acetamide 
• 620972-32-9 N-[2-(3-benzyl-2-cyclobutyl-3H-imidazol-4-yl)-ethyl]-2,2,2-trifluoro-acetamide 
• 620972-30-7 N-[2-(3-benzyl-2-tert-butyl-3H-imidazol-4-yl)-ethyl]-2,2,2-trifluoro-acetamide 
• 620972-33-0 N-[2-(3-benzyl-2-cyclopropyl-3H-imidazol-4-yl)-ethyl]-2,2,2-trifluoro-acetamide 
• 195053-92-0 1-(Triphenylmethyl)-4-(2-amino-1-ethyl)imidazole 

Relevant academic research and scientific papers

GLP RECEPTOR AGONISTS

The disclosures herein relate to novel compounds of formula (1 ): and salts thereof, wherein Q, W, X, Y, Z, AA1, AA2, AA3, AA4, AA5, AA6, AA7, AA8, AA9, LysR, R1, R2 and n are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with Glucagon-like peptide (GLP) receptors.

ORAL GLP RECEPTOR AGONISTS

The disclosures herein relate to novel compounds of formula (1a) or formula (1b): and salts thereof, wherein S, T, W, Z, AA1, AA2, AA3, AA4, AA5, AA6, AA7, AA8, AA9, AA10, AA11, AA12, AA13, AA14, AA15, A16, AA17, AA18, AA19, AA20, AA21, AA22, Sa, Ta, Wa, Xa, Ya, Za, AA1a, AA2a, AA3a, AA4a, AA 5a, AA 6a,AA 7a,AA8a,AA 9a,AA 10a,AA11a,AA 12a,AA13aAA 14a,AA15a,AA 16a, R, R1 and R2 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with Glucagon-like peptide (GLP) receptors.

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

Four new imidazole-based ligands, 4-((1H-imidazol-4-yl)methyl)-2-phenyl-4,5-dihydrooxyzole (LOL1), 4-((1H-imidazol-4-yl)methyl)-2-(tert-butyl)-4,5-dihydrooxyzole (LOL2), 4-((1H-imidazol-4-yl)methyl)-2-methyl-4,5-dihydrooxyzole (LOL3), and N-(2,2-dimethylpropylidene)-2-(1-trityl-1H-imidazol-4-yl-)ethyl amine (Limz1), have been synthesized. The corresponding copper(I) complexes [Cu(I)(LOL1)(CH3CN)]PF6 (CuLOL1), [Cu(I)(LOL2)(CH3CN)]PF6 (CuLOL2), [Cu(I)(LOL3)(CH3CN)]PF6 (CuLOL3), [Cu(I)(Limz1)(CH3CN)2]PF6 (CuLimz1) as well as the Cu(I) complex derived from the known ligand bis(1-methylimidazol-2-yl)methane (BIMZ), [Cu(I)(BIMZ)(CH3CN)]PF6 (CuBIMZ), are screened as catalysts for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC-H2) to 3,5-di-tert-butylquinone (3,5-DTBQ). The primary reaction product of these oxidations is 3,5-di-tert-butylsemiquinone (3,5-DTBSQ) which slowly converts to 3,5-DTBQ. Saturation kinetic studies reveal a trend of catalytic activity in the order CuLOL3?≈?CuLOL1?>?CuBIMZ?>?CuLOL2?>?CuLimz1. Additionally, the catalytic activity of the copper(I) complexes towards the oxygenation of monophenols is investigated. As substrates 2,4-di-tert-butylphenol (2,4-DTBP-H), 3-tert-butylphenol (3-TBP-H), 4-methoxyphenol (4-MeOP-H), N-acetyl-l-tyrosine ethyl ester monohydrate (NATEE) and 8-hydroxyquinoline are employed. The oxygenation products are identified and characterized with the help of UV/Vis and NMR spectroscopy, mass spectrometry, and fluorescence measurements. Whereas the copper complexes with ligands containing combinations of imidazole and imine functions or two imidazole units (CuLimz1 and CuBIMZ) are found to exhibit catalytic tyrosinase activity, the systems with ligands containing oxazoline just mediate a stoichiometric conversion. Correlations between the structures of the complexes and their reactivities are discussed.

DOUBLE-ACYLATED GLP-1 DERIVATIVES

The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1 (7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1 (7-37), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37), wherein the first K residue is designated K37, and the second K residue is designated K26, which derivative comprises two albumin binding moieties attached to K26 and K37, respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: ????????Chem. 1:?????HOOC-(CH2)x-CO-* ????????Chem. 2:?????HOOC-C6H4-O-(CH2)y-CO-* ????????Chem. 3:?????R1-C6H4-(CH2)z-CO-* ????????Chem. 4:?????HOOC-C4SH2-(CH2)w-CO-* in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, R1 is a group having a molar mass not higher than 150 Da, and w is an integer in the range of 6-18; with the proviso that when the protracting moiety is Chem. 1, the albumin binding moiety further comprises a linker of formula Chem. 5: *-NH-(CH2)2-(O-(CH2)2)k-O-(CH2)n-CO-*, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.

1,3 AND 1,3,5 SUBSTITUTED IMIDAZOLES AS ANTIHYPERTENSIVES

The present invention provides novel 1,5 and 1,3,5-substituted imidazole compounds of formulas (I), (IIa), (IIIb) in hydrophilic or lipophilic form, which are useful as angiotensin II AT1 receptor antagonists with sympathetic suppressant properties. In particular, the invention provides pharmaceutical compositions containing the pharmacophoric groups of Losartan and Clonidine as well compounds, processes and intermediates for preparing compounds and their use in methods of treating hypertension and cardiovascular diseases through Renin Angiotensin System (RAS) and Sympathetic System (SS). Alkylated histamine based double action Saltans are lipophilic and can act transdermally.

Trityl-directed regiospecific synthesis of 2,3-disubstituted bioimidazoles

We report an efficient trityl-directed regiospecific synthesis of 2,3-disubstituted-L-histdines and 2,3-disubstituted histamines starting from α-N-trifluoroacetyl-L-histidine methyl ester and α-N-trifluoroacetylhistamine respectively in five steps.

INHIBITORS OF PRENYL-PROTEIN TRANSFERASE

The present invention is directed to peptidomimetic piperazine-containing macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras

Potent inhibitors of farnesyltransferase and geranylgeranyltransferase-I

Compound 1 has been shown to be a dual prenylation inhibitor with FPTase (IC50=2 nM) and GGPTase-I (IC50=95 nM). Analogues of 1, which replaced the cyanophenyl group with various biaryls, led to the discovery of highly potent dual FPTase/GGPTase-I inhibitors. 4-Trifluoromethylphenyl, trifluoropentynyl, and trifluoropentyl were identified as good p-cyano replacements.