54157-11-8

Upstream product

• 3891-07-4 N-(2-Hydroxyethyl)phthalimide 
• 76-83-5 trityl chloride 
• 248597-85-5 N-(trifluoroacetyl)-O-(trityl)-ethanolamine 
• 2002-24-6 2-amino-ethanol hydrochloride 

Downstream Products

• 109875-63-0 Benzoic acid (2R,3S,5R)-2-[(2-chloro-phenoxy)-(2-trityloxy-ethylamino)-phosphoryloxymethyl]-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-tetrahydro-furan-3-yl ester 
• 109875-62-9 Benzoic acid (2R,3S,5R)-2-[(2-chloro-phenoxy)-(2-trityloxy-ethylamino)-phosphoryloxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 
• 109894-55-5 Benzoic acid (2R,3S,5R)-5-(4-benzoylamino-2-oxo-2H-pyrimidin-1-yl)-2-[(2-chloro-phenoxy)-(2-trityloxy-ethylamino)-phosphoryloxymethyl]-tetrahydro-furan-3-yl ester 
• 109894-54-4 Benzoic acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-[(2-chloro-phenoxy)-(2-trityloxy-ethylamino)-phosphoryloxymethyl]-tetrahydro-furan-3-yl ester 
• 109875-67-4 (2-Trityloxy-ethyl)-phosphoramidic acid 2-chloro-phenyl ester (2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 
• 109875-69-6 Phosphoric acid (2R,3S,5R)-2-[(2-chloro-phenoxy)-(2-trityloxy-ethylamino)-phosphoryloxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-chloro-phenyl ester 
• 114744-18-2 (2-Trityloxy-ethyl)-phosphoramidic acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl ester 2-chloro-phenyl ester 
• 114744-24-0 Phosphoric acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-[(2-chloro-phenoxy)-(2-trityloxy-ethylamino)-phosphoryloxymethyl]-tetrahydro-furan-3-yl ester 2-chloro-phenyl ester 
• 114765-65-0 C₅₉H₅₆Cl₂N₆O₁₅P₂ 
• 1427722-38-0 (-)-tert-butyl (S)-3-(2-(trityloxy)ethylamino)-3-(1-(tert-butoxycarbonyl)indol-3-yl)propanoate 
• 1427722-39-1 (-)-tert-butyl (R)-3-(2-(trityloxy)ethylamino)-3-(1-(tert-butoxycarbonyl)indol-3-yl)propanoate 
• 1427722-36-8 (N-tert-butyldimethylsilyl)[2-(trityloxy)ethyl]amine 
• 110545-34-1 Phosphoric acid (2R,3S,5R)-5-(6-amino-purin-9-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl ester (2R,3S,5R)-2-[hydroxy-(2-trityloxy-ethylamino)-phosphoryloxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 

Relevant academic research and scientific papers

Histone H4-based peptoids are inhibitors of protein arginine methyltransferase 1 (PRMT1)

Methylation of arginine residues occurs on a number of protein substrates, most notably the N-terminal tails of histones, and is catalyzed by a family of enzymes called the protein arginine methyltransferases (PRMTs). This modification can lead to transcriptional activation or repression of cancer-related genes. To date, a number of inhibitors, based on natural peptide substrates, have been developed for the PRMT family of enzymes. However, because peptides are easily degraded in vivo, the utility of these inhibitors as potential therapeutics is limited. The use of peptoids, which are peptide mimetics where the amino acid side chain is attached to the nitrogen in the amide backbone instead of the α-carbon, may circumvent the problems associated with peptide degradation. Given the structural similarities, peptoid scaffolds may provide enhanced stability, while preserving the mechanism of action. Herein, we have identified that peptoids based on natural peptide substrates are not catalyzed to the product by PRMT1, but instead are inhibitors of this enzyme. Reducing the length of the peptoid reduces inhibition and suggest the residues distal from the site of modification are important for binding. Furthermore, a positive charge on the N-terminus helps promote binding and improves inhibition. Selectivity among family members is likely possible based on inhibition being moderately selective for PRMT1 over PRMT5 and provides a scaffold that can be used to develop pharmaceuticals against this class of enzymes.

MELANIN PRODUCTION INHIBITOR

Disclosed is a melanin production inhibitor which has an excellent inhibitory activity on the production of melanin and is highly safe. The melanin production inhibitor is represented by general formula (1) (excluding clotrimazole) and/or a pharmacologically acceptable salt thereof. In the formula, A1, A2 and A3 are independently selected from a hydrogen atom, an aryl group which may have a substituent, and an aromatic heterocyclic group which may have a substituent. At least one of A1, A2 and A3 is selected from the aryl group and the aromatic heterocyclic group, the total number of carbon atoms contained in A1, A2 and A3 is 6 to 50 and, when at least two of A1, A2 and A3 represent the aryl groups or the aromatic heterocyclic groups, the adjacent two aryl or aromatic heterocyclic groups may be bound to each other via an alkyl chain or an alkenyl chain to form a ring; m represents an integer of 0 to 2; X represents a hetero atom, a hydrogen atom, or a carbon atom; R1 and R2 are independently selected from a hydrogen atom and an oxo group. When one of R1 and R2 is an oxo group, the other is not present. R3 is selected from a hydrogen atom, and a C1-8 hydrocarbon group in which one or some of hydrogen atoms or carbon atoms may be substituted by a hetero atom or hetero atoms. The number of R3's present in the compound corresponds to X and, when two or more R3's are present, the R3's are independently present and the adjacent two R3's may be bound to each other to form, together with X, a ring, and the terminal of R3 may be bound to a carbon atom to which A1, A2 and A3 are bound, thereby forming a ring.

Triphenylbutanamines: Kinesin spindle protein inhibitors with in vivo antitumor activity

The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-l-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit Kiapp ≥ 10 nM and GI50 ≈ 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.

MELANIN PRODUCTION INHIBITOR

Disclosed is a melanin production inhibitor which has an excellent inhibitory activity on the production of melanin and is highly safe. The melanin production inhibitor comprises a compound represented by general formula (1) (excluding clotrimazole), and/or a pharmacologically acceptable salt thereof. In the formula, A1, A2 and A3 are independently selected from a hydrogen atom, an aryl group which may have a substituent, and an aromatic heterocyclic group which may have a substituent, wherein at least one of A1, A2 and A3 is selected from the aryl group and the aromatic heterocyclic group, the total number of carbon atoms contained in A1, A2 and A3 is 6 to 50 and, when at least two of A1, A2 and A3 represent the aryl groups or the aromatic heterocyclic groups, the adjacent two aryl or aromatic heterocyclic groups may be bound to each other via an alkyl chain or an alkenyl chain to form a ring; m represents an integer of 0 to 2; X represents a hetero atom, a hydrogen atom, or a carbon atom; R1 and R2 are independently selected from a hydrogen atom and an oxo group, wherein when one of R1 and R2 is an oxo group, the other is not present; and R3 is selected from a hydrogen atom, and a C1-8 hydrocarbon group in which one or some of hydrogen atoms or carbon atoms may be substituted by a hetero atom or hetero atoms, wherein the number of R3's present in the compound corresponds to the number of X's and, when two or more R3's are present, the R3's are independently present and the adjacent two R3's may be bound to each other to form, together with X, a ring, and the terminal of R3 may be bound to a carbon atom to which A1, A2 and A3 are bound, thereby forming a ring.

Reductive demercuration in deprotection of trityl thioethers, trityl amines, and trityl ethers

A room-temperature deprotection method of trityl amines, -ethers, and -thioethers is presented, based on coupling of metal acid catalysis (HgX2, with X- = Cl- or OAc-) and sodium borohydride reduction. The results of its application to monotritylated compounds (ethanethiol, ethanol, and piperidine) and to mono- and ditritylated 1,2-bifunctional compounds (mercaptoethanol, aminoethanethiol, and ethanolamine) are compared with those obtained with early methods based on the use of strong Bronsted acids (pure TFA and MeCN solutions of HCl). Trityl thioethers of simple thiols and amino and hydroxy thiols are promptly cleaved by reductive detritylation, and one-pot procedures can be employed to produce free thiols. In contrast, dilution with water of these same compounds in solutions of strong Bronsted acids leaves them unaffected. O-Tr and N-Tr bonds are broken by this latter treatment. However, trityl ethers are rapidly cleaved by even dilute HCl solutions, while cleaving of trityl amines is modulated by HCl concentration. Addition of NaBH4 to solutions of monofunctional trityl ethers in HgCl2/MeCN leads to complete deprotection. Monofunctional trityl amines are partially deprotected only if the complexation reaction is allowed to reach equilibrium. Combination of H+- with HgX+-catalyzed detritylation methods allows selective deprotection of pertritylated amino and hydroxy thiols. The results appear to be due to the strong difference in the affinity of the donor atoms present in the pertritylated substrates for H+ and HgX+. Catalysis based on Bronsted acids leads to cleaving of the N- and O-trityl bonds with recovering of the S-trityl group; that based on mercury salts allows recovering of N- and O-trityl groups with deprotection of the -SH function. Selectivity in deprotection of pertritylated amino alcohols seems to be severely hampered by similarity in the affinity of N- and O-atoms for H+ and HgX+, and, taking advantage of the lower HgX+-complexation rate of the N-trityl with respect to the O-trityl group, only preservation of the N-trityl bond has been achieved.

TRITYLOXYETHYLAMINO GROUP FOR THE PROTECTION OF PHOSPHORYL GROUP IN OLIGONUCLEOTIDE SYNTHESIS

Trityloxyethylamino group was used for the protection of 5'-phosphoryl group of deoxyribonucleoside.This group is not only protecting group of phosphate also the intermediate for the synthesis of d-ppA and d-pppA.