Day: December 6, 2022

Santandrea, Ernesto published the artcileDevelopment of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge, Product Details of C4H3Cl2N3, the publication is Organic Process Research & Development (2021), 25(5), 1190-1205, database is CAplus.

The development of the late-phase manufacturing process of the drug candidate ZPL389 and the strategies for the control of impurities are outlined in detail. Selective salt formation at several stages was pivotal to controlling the process impurities. The extensive optimization of the N-methylation of a Boc-protected amine with di-Me sulfate and of a nucleophilic aromatic substitution without the use of metal catalysts led to a robust, scalable process. The process was demonstrated on a >100 kg scale. Overall, improved drug substance quality, higher yield, and reduction of the process mass intensity were achieved.

Organic Process Research & Development published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Product Details of C4H3Cl2N3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Giordanetto, Fabrizio published the artcileDiscovery of phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, an effective antithrombotic agent without associated bleeding and insulin resistance, SDS of cas: 56-05-3, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(21), 6671-6676, database is CAplus and MEDLINE.

Structure-based evolution of the original fragment leads resulted in the identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor with favorable in vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not significantly increase bleeding time in dogs. Addnl., due to its enhanced selectivity over p110α, (S)-21 did not induce any insulin resistance in rats.

Bioorganic & Medicinal Chemistry Letters published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, SDS of cas: 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Harisha, S. published the artcileClinical trials of water based compositions of active hair growth stimulants in the treatment of alopecia, Computed Properties of 74638-76-9, the publication is European Journal of Biomedical and Pharmaceutical Sciences (2014), 1(3), 284-305, database is CAplus.

Background: Androgenic Alopecia (AGA): Androgenic alopecia (also known as Androgenetic alopecia or Alopecia androgenetica), in male humans in particular this condition is also commonly known as male pattern baldness, hereditary alopecia and simply common baldness. Pathophysiol.: Androgenetic alopecia is a genetically determined disorder and is progressive through the gradual conversion of thick terminal hairs with fine, miniaturized hairs that are eventually lost. Patients with this disorder usually have a typical patterned distribution of hair loss. In Androgenetic alopecia, Studies have indicated a self-renewal of the hair follicle via keratinocyte stem cells located at the area of the bulge of the hair follicle. In addition, a series of studies using mice has indicated that interfollicular keratinocyte stem cells could generate de novo hair follicles in adult mouse skin. These regenerated hair follicles cycled through stages of telogen to anagen. However, these transitions between bulge and epidermal keratinocytes have not been seen yet in human studies. Another report has indicated that mice lacking in functional vitamin D receptors develop a functional first coat of hair, but lack the cyclic regeneration of hair follicles leading to the development alopecia. Whether these findings will lead to a new area of exploration into the cause of Androgenetic alopecia in humans is unknown at this time. Primary objective: To evaluate the Efficacy of topical application of study drug for the treatment of mild to moderate Androgenic Alopecia in Male Patients. Secondary objective: To evaluate the safety of topical application of study drug for the treatment of mild to moderate Androgenic Alopecia in Male Patients. Methods: Subjects were enrolled as per the inclusion and exclusion criteria. All the subjects were then randomized in to 5 different groups. Drug A= FD/SBF/MX-40* Drug B- FD/SBF/PY-39* Drug C- FD/WBF/MX-36* Drug D- FD/WBF/PY-37* Drug E- FD/WBF/KX-38* *Study samples provided by “Kumar Organic Products,Research Center Private Limited”.

European Journal of Biomedical and Pharmaceutical Sciences published new progress about 74638-76-9. 74638-76-9 belongs to pyrimidines, auxiliary class Pyrimidine, name is 2,4-Diaminopyrimidine-3-oxide, and the molecular formula is C4H6N4O, Computed Properties of 74638-76-9.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Staedeli, Werner published the artcileNitrogen-15 spectroscopy. Part 5. Nitrogen-15 NMR studies of aminopyridines, aminopyrimidines and of some diazine N-oxides, Formula: C4H6N4O, the publication is Helvetica Chimica Acta (1980), 63(2), 504-22, database is CAplus.

¹⁵N NMR spectra were obtained in neutral and acidic media for mono- and diaminopyridines, and mono-, di-, and triaminopyrimidines. Ring N shifts are discussed in terms of β-, χ-, and δ-substituent effects of amino and alkyl groups. Protonation states in trifluoroacetic acid and FSO₃H solution and protonation effects on the ¹⁵N NMR spectra are determined A linear correlation is observed between amino substituent effects on the ring N-atom in aminopyridines and the corresponding ¹³C values in aminobenzenes, and, similarly, between ¹⁵N values in aminopyrimidines and ¹³C values in aminopyridines. One-bond ¹⁵N-H coupling constants for aminopyridines and aminopyrimidines are discussed in terms of conjugative interaction between NH₂ groups and the ring system.

Helvetica Chimica Acta published new progress about 74638-76-9. 74638-76-9 belongs to pyrimidines, auxiliary class Pyrimidine, name is 2,4-Diaminopyrimidine-3-oxide, and the molecular formula is C11H24O3, Formula: C4H6N4O.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Nim-anussornkul, Duangrat published the artcileSynthesis and optical properties of pyrrolidinyl peptide nucleic acid bearing a base discriminating fluorescence nucleobase 8-(pyrene-1-yl)-ethynyladenine, Application In Synthesis of 186046-81-1, the publication is Bioorganic & Medicinal Chemistry (2017), 25(24), 6388-6397, database is CAplus and MEDLINE.

A combination of fluorophore and nucleobase through a π-conjugated rigid linker integrates the base pairing and the fluorescence change into a single event. Such base discriminating fluorophore can change its fluorescence as a direct response to the base pairing event and therefore have advantages over tethered labels or base surrogates lacking the hydrogen-bonding ability. 8-(Pyrene-1-yl)ethynyl-adenine (A^PyE) has been extensively used as fluorescence labels in DNA and LNA, but it showed little discrimination between different nucleobases. Herein we investigated the synthesis, base pairing ability and optical properties of A^PyE in pyrrolidinyl peptide nucleic acid – a DNA mimic that shows much stronger affinity and specificity towards DNA than natural oligonucleotides. The A^PyE in PNA pairs specifically with thymine in the DNA strand, and resulted in 1.5-5.2-fold enhanced and blue-shifted fluorescence emission. Fluorescence quenching was observed in the presence of mismatched base or abasic site directly opposite to the A^PyE. The behavior of A^PyE in acpcPNA is distinctively different from DNA whereby a fluorescence was increased selectively upon duplex formation with complementary DNA and therefore emphasizing the unique advantages of using PNA as alternative oligonucleotide probes. Applications as color-shifting probe for detection of trinucleotide repeats in DNA were demonstrated, and the performance of the probe was further improved by combination with reduced graphene oxide as an external nano-quencher.

Bioorganic & Medicinal Chemistry published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Application In Synthesis of 186046-81-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Nim-anussornkul, Duangrat published the artcileSynthesis and optical properties of pyrrolidinyl peptide nucleic acid bearing a base discriminating fluorescence nucleobase 8-(pyrene-1-yl)-ethynyladenine, Product Details of C26H26N4O7, the publication is Bioorganic & Medicinal Chemistry (2017), 25(24), 6388-6397, database is CAplus and MEDLINE.

A combination of fluorophore and nucleobase through a π-conjugated rigid linker integrates the base pairing and the fluorescence change into a single event. Such base discriminating fluorophore can change its fluorescence as a direct response to the base pairing event and therefore have advantages over tethered labels or base surrogates lacking the hydrogen-bonding ability. 8-(Pyrene-1-yl)ethynyl-adenine (A^PyE) has been extensively used as fluorescence labels in DNA and LNA, but it showed little discrimination between different nucleobases. Herein we investigated the synthesis, base pairing ability and optical properties of A^PyE in pyrrolidinyl peptide nucleic acid – a DNA mimic that shows much stronger affinity and specificity towards DNA than natural oligonucleotides. The A^PyE in PNA pairs specifically with thymine in the DNA strand, and resulted in 1.5-5.2-fold enhanced and blue-shifted fluorescence emission. Fluorescence quenching was observed in the presence of mismatched base or abasic site directly opposite to the A^PyE. The behavior of A^PyE in acpcPNA is distinctively different from DNA whereby a fluorescence was increased selectively upon duplex formation with complementary DNA and therefore emphasizing the unique advantages of using PNA as alternative oligonucleotide probes. Applications as color-shifting probe for detection of trinucleotide repeats in DNA were demonstrated, and the performance of the probe was further improved by combination with reduced graphene oxide as an external nano-quencher.

Bioorganic & Medicinal Chemistry published new progress about 169396-92-3. 169396-92-3 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide,Others,PNA, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C26H26N4O7, Product Details of C26H26N4O7.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Ruiz Ruiz, Maria del Carmen published the artcileThe ‘t-Amino Effect’ of ortho-nitroso amines. synthesis of 2,6-diaminoadenine derivatives from 6-(dialkylamino)-5-nitrosopyrimidines, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is Helvetica Chimica Acta (2011), 94(5), 785-800, database is CAplus.

The ‘t-amino effect’ of amino-nitroso compounds was documented by preparing the (dialkylamino)-nitroso pyrimidines, and cyclising them under thermal conditions in high yields to the purine derivatives e. g., I(R¹ = Me, R² = H, Me, Pr, Ph; R¹ = Et, R² = Me; R¹ = CO₂Et, R² = CH₂CO₂Et) and II. The reactivity of the amino-nitroso-pyrimidines, particularly of 17 derived from di-Et iminodiacetate, and of I(R¹ = CO₂Et, R² = CH₂CO₂Et), derived from 1-phenylimidazolidine, correlates with the stability of the intermediate azomethine ylide. Thermolysis of the amino-nitroso-pyrimidines III(R¹ = NO, R² = 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 4-Et isonipecotate-1yl) possessing dialkylamino substituents at C(4) and C(6), proceeded by protiodenitrosation, leading to III(R¹ = H, R² = 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 4-Et isonipecotate-1yl).

Helvetica Chimica Acta published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Safety of 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Michaelis, Julia published the artcileDNA-Triggered Dye Transfer on a Quantum Dot, Safety of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, the publication is Bioconjugate Chemistry (2014), 25(1), 18-23, database is CAplus and MEDLINE.

Nucleic acid-templated reactions are frequently explored tools in nucleic acid diagnosis. To enable a separation-free DNA detection, the reactive probe mols. require conjugation with reporter groups that provide measurable changes of an observable parameter upon reaction. A widely used, generic read-out method is based on fluorescence resonance energy transfer (FRET) between two appended dyes. Yet, spectral cross-talk usually limits the achievable enhancements of the FRET signal in DNA-directed chemistries. We describe a DNA-triggered transfer reaction which provides for strong increases of a fluorescent signal caused by FRET. The method may involve DNA- and PNA-based probes and is based upon a proximity-triggered transfer reaction which leads to the covalent fixation of a fluorescence dye on the surface of a quantum dot (QD). The transfer reaction brings the dye closer to the QD than hybridization alone. The resulting FRET signal is a specific monitor of the reaction and allows efficient discrimination of single base mismatched templates. Of note, the 35-fold increase of the FRET signal is measured at 310 nm apparent Stokes shift and turnover in template provides a means for signal amplification.

Bioconjugate Chemistry published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Safety of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Michaelis, Julia published the artcileDNA-Triggered Dye Transfer on a Quantum Dot, Product Details of C26H26N4O7, the publication is Bioconjugate Chemistry (2014), 25(1), 18-23, database is CAplus and MEDLINE.

Nucleic acid-templated reactions are frequently explored tools in nucleic acid diagnosis. To enable a separation-free DNA detection, the reactive probe mols. require conjugation with reporter groups that provide measurable changes of an observable parameter upon reaction. A widely used, generic read-out method is based on fluorescence resonance energy transfer (FRET) between two appended dyes. Yet, spectral cross-talk usually limits the achievable enhancements of the FRET signal in DNA-directed chemistries. We describe a DNA-triggered transfer reaction which provides for strong increases of a fluorescent signal caused by FRET. The method may involve DNA- and PNA-based probes and is based upon a proximity-triggered transfer reaction which leads to the covalent fixation of a fluorescence dye on the surface of a quantum dot (QD). The transfer reaction brings the dye closer to the QD than hybridization alone. The resulting FRET signal is a specific monitor of the reaction and allows efficient discrimination of single base mismatched templates. Of note, the 35-fold increase of the FRET signal is measured at 310 nm apparent Stokes shift and turnover in template provides a means for signal amplification.

Bioconjugate Chemistry published new progress about 169396-92-3. 169396-92-3 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide,Others,PNA, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C26H26N4O7, Product Details of C26H26N4O7.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Beall, Edward published the artcileEffects of the backbone and chemical linker on the molecular conductance of nucleic acid duplexes, Safety of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, the publication is Journal of the American Chemical Society (2017), 139(19), 6726-6735, database is CAplus and MEDLINE.

Scanning tunneling microscope break junction measurements were used to examine how the mol. conductance of nucleic acids depends on the composition of their backbone and the linker group to the electrodes. Mol. conductances of 10 base-pair-long homoduplexes of DNA, aeg-PNA, γ-PNA, and a heteroduplex of DNA/aeg-PNA with identical nucleobase sequence were measured. The mol. conductance was found to vary by 12-13-fold with the change in backbone. Computational studies showed that the mol. conductance differences between nucleic acids of different backbones correlated with differences in backbone structural flexibility. The mol. conductance was also measured for duplexes connected to the electrode through 2 different linkers, one directly to the backbone and one directly to the nucleobase stack. While the linker caused an order-of-magnitude increase in the overall conductance for a particular duplex, the differences in the elec. conductance with backbone composition were preserved. The highest mol. conductance value(0.06G₀) was measured for aeg-PNA duplexes with a base stack linker. These findings revealed an important new strategy for creating longer and more complex electroactive, nucleic acid assemblies.

Journal of the American Chemical Society published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Safety of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia