Barbiturates And Minor Tranquilizers
S.J. Mulé, Henry Brill in Chemical and Biological Aspects of Drug Dependence, 2019
The major route of synthesis of chlordiazepoxide and other derivatives, as shown in Figure 8, is via a ring enlargement of quinazoline 3-oxides with either a primary aliphatic amine or hydrazine.49,54 “ 56 Several 2-amino-l, 4-benzodiazepine derivatives may also be fabricated from this type of chemical reation by utilizing substituted quinazoline 3-oxides, in which R may be a phenyl or a substituted phenyl,54-56 2- or 4-pyridyl,5.7 2-thienyl,56 hydrogen,49 alkyl,49 or cyclohexyl56 group. In addition, X at the number 6 carbon may be a alkylthio,58 chlorine,54–56 bromine,55 hydrogen,55,56 methyl,55,56 methoxycarbonyl,49 nitro,59 or a trifluoromethyl substituted group.49 Although quinazoline 3-oxide derivatives are primarily reacted with primary amines to cause the enlargement of a ring from a 6 to a 7 membered structure, a similar reaction may occur with some secondary amines.51 The two weak basic amines that have been utilized are dimethylamine60 and pyrrolidine,49 thereby resulting in a compound with a tertiary amine in the number 2 position. The leaving group at the number 2 position of quinazoline is usually chlorine.54-56
Proteases as Biocatalysts for the Synthesis of Model Peptides
Willi Kullmann in Enzymatic Peptide Synthesis, 1987
Structural patterns of the amine components also played a decisive role in the following studies.69-71 Again it was observed that amino acid amides are better nucleophilic acceptors than free amino acids. Additionally, d-amino acids, dipeptides, and secondary amides were shown to be inappropriate amine components.69 The use of amino acid alkyl esters as amine components in the presence of Nα-blocked amino acid and peptide methyl esters as carboxyl components permitted the synthesis of the intended peptides. However, in many cases byproducts with an extended chain length were also created.70 In fact surplus amino acid residues were incorporated into the products by random oligomerization of the amine components; the methyl esters of hydrophobic amino acid residues in particular being involved in this side reaction, whereas hydrophilic amino acid methyl esters were oligomerized only to a minor extent. The degree of oligomerization, however, could be reduced both by enlarging the alkyl ester moiety of the amine component and by employing phenylmercuric chloride-treated carboxypeptidase Y.71 In addition, this latter study revealed that benzylated ester donors may serve the function of a carboxyl component more efficiently than the corresponding methyl esters. This effect was observed for instance with the benzylated alanine derivative Bz-Ala-Bzl which proved to be strikingly superior as an acyl group donor in comparison to its methylated analog Bz-Ala-OMe.
Conditioning of Hair
Dale H. Johnson in Hair and Hair Care, 2018
While the tertiary alkyl amines have been used extensively as conditioning agents, more recently the amido amine structure shown in Figure 1 has gained favor over the tertiary amine because of its performance advantages. Both amines and amido amines contain a long alkyl group, but in the case of the amido amine, an amido group is inserted between the nitrogen and the alkyl group. The presence of an amido group radically influences the functional differences between amines and amido amines. Concentration of positive charge on the hydrophobic portion of the molecule imparts strong cationic properties. At an acidic pH, the amine group becomes protonated and the character changes from water-insoluble to water-soluble. Friedli (22) discusses the organic chemistry of amido amines in detail.
Pharmacokinetic evaluation of quetiapine fumarate controlled release hybrid hydrogel: a healthier treatment of schizophrenia
Published in Drug Delivery, 2018
Muhammad Akhlaq, Faiza Maryam, Abdelhamid Elaissari, Hashmat Ullah, Muhammad Adeel, Abid Hussain, Muhammad Ramzan, Obaid Ullah, Muhammad Zeeshan Danish, Shehla Iftikhar, Nighat Aziz
Swelling increases as the quantity of Gel increases. The functional groups of Gel responsible for swelling of hydrogels are amine (–NH2) and carboxylic acid group (–COOH) (Raafat, 2010). Amine contains basic nitrogen and is basically a derivative of ammonia with one or more hydrogen atom(s) replaced by alkyl or aryl group. At pH below pKb of basic components (acidic pH), ionization (protonation) occurs that results in formation of –NH3+ ions and due to the presence of similar cations, electrostatic repulsion takes place within them resulting in swelling of hydrogel in acidic medium (Gil et al., 2005). Gel also contains -COOH group which is an acidic component and at pH above pKa (basic medium) loses H + ion thus becomes COO−, ionization of COOH group at pH 7.4 causes the repulsion of anions due to electrostatic repulsion and thus swelling of the hydrogel occurs in basic medium. Because of the presence of these functional groups, Gel/HPMC hydrogel showed swelling at both acidic and basic pH (Lou & Chirila, 1999).
Identification of a dual TAOK1 and MAP4K5 inhibitor using a structure-based virtual screening approach
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Min-Wu Chao, Tony Eight Lin, Wei-Chun HuangFu, Chao-Di Chang, Huang-Ju Tu, Liang-Chieh Chen, Shih-Chung Yen, Tzu-Ying Sung, Wei-Jan Huang, Chia-Ron Yang, Shiow-Lin Pan, Kai-Cheng Hsu
To determine the molecular interactions between the identified inhibitors and MAP4K5, we performed an interaction analysis using the molecular software LeadIT33. For clarity, the compounds are separated into three sub-structures. The S1 sub-structure (2-aminopyrimidine) of compound 1 forms hydrogen bonds with the nitrogen and oxygen of MAP4K5 hinge residue C78. Formation of hydrogen bonds with hinge residues is typical for small-molecule kinase inhibitors targeting the binding site 37. The cyclic nitrogen acts as a hydrogen acceptor, while the amine acts as a hydrogen donor for the nitrogen and oxygen backbone of C78, respectively (Figure 3(A)). The sub-structures S2 and S3, which form the terminal ends of compound 1, also form hydrogen bonds (Figure 3(A)). Two hydrogen bonds are formed betweenresidue D85 and the phenol of the sub-structure S2. The phenol of sub-structure S2 is attached to an imidazo[2,1-b][1,3]thiazole. Residue Y77 forms a hydrogen bond with the 1,2,5-thiadiazolidine 1,1-dioxide of the S3 sub-structure (Figure 3(A)). Hydrophobic interactions also occur within the MAP4K5 binding site. For example, residue A128 forms hydrophobic interactions with the S1 sub-structure. The S2 sub-structure creates hydrophobic contacts with residues V7 and A138, while the S3 sub-structure is sandwiched by hydrophobic interactions with residues V7, V15, L128 (Figure 3(A)).
PDE1 inhibitors: a review of the recent patent literature (2008-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Mei-Ling Le, Mei-Yan Jiang, Chuan Han, Yi-Yi Yang, Yinuo Wu
In 2015, Kehler and coworkers disclosed a series of PDE1 inhibitors with quinazoline scaffold (Figure 27). The X group on the quinazoline was a halogen atom in the first patent. The IC50 values of these compounds against PDE1 ranged from 7 nM to 2800 nM. Most compounds in this patent had two or more stereoisomers and one showed better inhibitory activities than others [79]. For the representative compound 86, stereoisomer 1 gave the IC50 value of 9.9 nM, while stereoisomer 2 gave the IC50 value of 65 nM against PDE1B. However, no configuration was provided for each stereoisomer. In another patent by Kehler, the X group on the quinazoline was instead by the methoxy group. The amine can be primary amine, secondary amine, or cyclic aliphatic amine [80]. The configuration had a significant impact on the inhibitory activities. For example, the (S)-87 was 30-fold more potent against PDE1B than (R)-87 [81].
Related Knowledge Centers
- Ammonia
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- Chemical Compound
- Chemistry
- Functional Group
- Substituent
- Amino Acid
- Nitrogen
- Hydrogen
- Trimethylamine