147081-44-5Relevant articles and documents
The identification and use of robust transaminases from a domestic drain metagenome
Leipold, Leona,Dobrijevic, Dragana,Jeffries, Jack W.E.,Bawn, Maria,Moody, Thomas S.,Ward, John M.,Hailes, Helen C.
, p. 75 - 86 (2019/01/11)
Transaminases remain one of the most promising biocatalysts for use in chiral amine synthesis, however their industrial implementation has been hampered by their general instability towards, for example, high amine donor concentrations and organic solvent content. Herein we describe the identification, cloning and screening of 29 novel transaminases from a household drain metagenome. The most promising enzymes were fully characterised and the effects of pH, temperature, amine donor concentration and co-solvent determined. Several enzymes demonstrated good substrate tolerance as well as an unprecedented robustness for a wild-type transaminase. One enzyme in particular readily accepted IPA as an amine donor giving the same conversion with 2-50 equivalents, as well as being tolerant to a number of co-solvents, and operational in up to 50% DMSO-a characteristic as yet unobserved in a wild-type transaminase. This work highlights the value of using metagenomics for biocatalyst discovery from niche environments, and here has led to the identification of one of the most robust native transaminases described to date, with respect to IPA and DMSO tolerance.
Economical synthesis of tert-butyl (S)-3-aminopyrrolidine-1-carboxylate from L-aspartic acid
Han, Zhi-Jian,Li, Yang-Bing,Gu, Bao-Hong,Li, Yu-Min,Chen, Hao
, p. 2452 - 2456 (2018/10/20)
3-Aminopyrrolidine building block was used as the intermediate for many pharmaceutically active substances. Starting from L-aspartic acid, optically active (S)-tert-butyl-3-aminopyrrolidine-1-carboxylate was synthesized, and the reaction conditions were optimized in each step. The procedure of each step was discussed in detail and could be useful for the industrial preparation. This process was featured by readily available starting material, mild reaction conditions, easy work-up, and economy.
Aromatic heterocyclic derivatives and applications of aromatic heterocyclic derivatives in medicines
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, (2016/10/09)
The present invention discloses aromatic heterocyclic derivatives and applications of the aromatic heterocyclic derivatives in medicines, and specifically provides a class of aromatic heterocyclic compounds or stereoisomers, geometric isomers, tautomers, racemic bodies, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions containing the compounds. The present invention further discloses uses of the compounds or pharmaceutical compositions in drug preparation, wherein the drug is used for treatment of respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).
HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
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Paragraph 00470, (2016/05/02)
Disclosed are heteroaryl derivatives, pharmaceutical composition and uses in the manufacture of a medicine for treating respiratory diseases, especially for chronic obstructive pulmonary disease (COPD).
Synthesis and evaluation of novel ligands for the histamine H4 receptor based on a pyrrolo[2,3-d]pyrimidine scaffold
Gao, Ling-Jie,Schwed, J. Stephan,Weizel, Lilia,De Jonghe, Steven,Stark, Holger,Herdewijn, Piet
, p. 132 - 137 (2013/02/23)
Starting from a known H4R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH4R (Ki = 0.5 μM), its lacks selectivity with a K i value for the hH3R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show Ki values of less than 1 μM at the hH4R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH4R ligands.
Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH 1R, but low affinity to hH4R
Wagner, Eva,Wittmann, Hans-Joachim,Elz, Sigurd,Strasser, Andrea
supporting information; experimental part, p. 6274 - 6280 (2011/11/29)
In literature, a synergism between histamine H1 and H 4 receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H1 antagonist and JNJ7777120, a H 4 receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H1 and one H4 pharmacophor, connected by an appropriate spacer, in order to address both, H1R and H 4R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH1R and hH4R. The new compounds revealed (high) affinity to hH1R, but showed only low affinity to hH4R. Additionally, we performed molecular dynamic studies for some selected compounds at hH1R, in order to obtain information about the binding mode of these compounds on molecular level.
CARBAPENEM ANTIBACTERIALS WITH GRAM-NEGATIVE ACTIVITY
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, (2012/01/06)
The present invention provides β-methyl carbapenem compounds and pharmaceutical compositions useful in the treatment of bacterial infections and methods for treating such infections using such compounds and/or compositions. The invention includes administering an effective amount of a carbapenem compound or salt and/or prodrug thereof to a host in need of such a treatment.
Anti-infective compounds
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, (2011/08/04)
The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
NOVEL 7-SUBSTITUTED 3-CARBOXY-OXADIAZINO-QUINOLONE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION AS ANTI-BACTERIALS
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Page/Page column 51, (2009/09/08)
A subject of the invention is the compounds of formula (I): in which either R1 represents H, OH, NH2, —(CH2)m—NRaRb(m=0.1 or 2),Ra and Rb represent H, linear, branched or cyclic (C1 -C6) alkyl, (C3-C6) cycloalkyl-(C3-C6)— alkyl, Rc, S(O)2Rc, C(O)Rc, S(O)2Rd or C(O)Rd;or Ra and Rb with N form an Rc radical;Rc represents a saturated, unsaturated or 5- or 6-members aromatic ring, containing 1 to 4 heteroatoms chosen from N, O and S, optionally substituted;Rd represents a linear, branched or cyclic (C1-C6) alkyl, optionally substituted by 1 to 4 halogens;or R1 represents Rc or CHReRc or CHReRd;Re represents H, OH, NH2, NH—(C1-C6)-alk or N-(C1-C6)-alk2, or NH—(C1-C7)-acyl or NHRc;R2 represents H, (CH2)m—NRaRb, Rc, CHReRc or CHReRd, and R′2 represents H; it being understood that R1 and R2 cannot at the same time be H or that R1 and R2 or R2 and R1 cannot be one (CH2)m—NRaRb or Rc or H and the other one OH, or one H and the other one NH2, or one H and the other one (CH2)m—NRaRb in which Ra and Rb represent H or alkyl or C(O)Rd, in which Rd represents an unsubstituted alkyl or cycloalkyl; or R1 has the above definition except H and R2 and R′2 together represent gem dialkyl or alkyl-oxime, or R2 and R′2 represent respectively Rc or Rd and OH, NH2, NHRc or NHRf, Rf being a (C1-C7) acyl radical;or R1 represents H and R2 and R′2 together represent alkyl-oxime or one represents Rc and the other one represents OH, NH2, NHRc or NHRf;n is 0 or 1;R3 and R′3 represent H or (C1-C6) alkyl optionally substituted by 1 to 3 halogens or R3 represents (C1-C6) alkoxy carbonyl and R′3 represents H;R4 represents methyl optionally substituted by halogen;R5 represents H, (C1-C6) alkyl or (C7-C12) arylalkyl;R6 represents H, fluorine, NO2, CF3 or CN;in the form of enantiomers or mixtures, as well as their salts with acids and bases; their preparation and their application as anti-bacterials, in both human and veterinary medicine.
