- An integrated console for capsule-based, automated organic synthesis
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The current laboratory practices of organic synthesis are labor intensive, impose safety and environmental hazards, and hamper the implementation of artificial intelligence guided drug discovery. Using a combination of reagent design, hardware engineering, and a simple operating system we provide an instrument capable of executing complex organic reactions with prepacked capsules. The machine conducts coupling reactions and delivers the purified products with minimal user involvement. Two desirable reaction classes-the synthesis of saturated N-heterocycles and reductive amination-were implemented, along with multi-step sequences that provide drug-like organic molecules in a fully automated manner. We envision that this system will serve as a console for developers to provide synthetic methods as integrated, user-friendly packages for conducting organic synthesis in a safe and convenient fashion. This journal is
- Bode, Jeffrey W.,Bordi, Samuele,Chen, Kuang-Yen,Jiang, Tuo,McMillan, Angus E.,Nichols, Paula L.,Saito, Fumito,Wanner, Benedikt M.
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p. 6977 - 6982
(2021/06/06)
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- Catalytic Synthesis of N-Unprotected Piperazines, Morpholines, and Thiomorpholines from Aldehydes and SnAP Reagents
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Commercially available SnAP (stannyl amine protocol) reagents allow the transformation of aldehydes and ketones into a variety of N-unprotected heterocycles. By identifying new ligands and reaction conditions, a robust catalytic variant that expands the substrate scope to previously inaccessible heteroaromatic substrates and new substitution patterns was realized. It also establishes the basis for a catalytic enantioselective process through the use of chiral ligands. SnAPcat! The identification of new ligands and reaction conditions provides a robust catalytic method for the synthesis of N-unprotected heterocycles using SnAP reagents. This catalytic variant expands the substrate scope to include previously inaccessible piperazines, morpholines, and thiomorpholines and establishes the basis for a catalytic enantioselective process through the use of chiral ligands.
- Luescher, Michael U.,Bode, Jeffrey W.
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supporting information
p. 10884 - 10888
(2015/09/15)
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- SnAP reagents for the synthesis of piperazines and morpholines
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Substituted piperazines and morpholines are valuable structural motifs in biologically active compounds, but are not easily prepared by contemporary cross-coupling approaches. In this report, we introduce SnAP reagents for the transformation of aldehydes into N-unprotected piperazines and morpholines. This approach offers simple, mild conditions compatible with aromatic, heteroaromatic, aliphatic, and glyoxylic aldehydes and provides mono- and disubstituted N-heterocycles in a single step.
- Luescher, Michael U.,Vo, Cam-Van T.,Bode, Jeffrey W.
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p. 1236 - 1239
(2014/03/21)
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- HETEROCYCLIC AMIDE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
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Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type or T-type calcium channel activity are disclosed. Specifically, a series of heterocyclic amides are disclosed of the general formula (I) where Z is N or CHNR2 and X is NR2, O, S, S=O or SO2. Among other definitions for R, R1, W and Y, the compounds of formula (1) are further characterized by at least one of W or Y being CR3Ar2 where Ar is an aromatic or heteroaromatic ring (for example, where W or Y is a benzhydryl moiety).
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Page/Page column 44
(2008/06/13)
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- INHIBITORS OF ALPHA-L BETA-2 MEDIATED CELL ADHESION
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The present invention relates to a compound of formula: (I), or a pharmaceutically acceptable salt thereof.
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Page/Page column 33
(2010/02/11)
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- 4-amino-quinazoline and quinoline derivatives having an inhibitory effect on signal transduction mediated by tyrosine kinases
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The present invention relates to bicyclic heterocycles of general formula wherein Ra to Rd, A to G and X are defined as in claim 1, the tautomers, the steroisomers and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibiting effect on signal transduction mediated by tyrosine kinases, their use for treating diseases, particularly tumoral diseases, diseases of the lungs and respiratory tract, and the preparation thereof.
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Page/Page column 67
(2008/06/13)
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- Carboxylic acids and the esters thereof, pharmaceutical compositions thereto and processes for the preparation thereof
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The present invention relates to carboxylic acids and esters of general formula wherein Ar, R, R1, X1, X3, X4, Y and Y1 are defined as in claim 1, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof, as well as the use thereof for the production and purification of antibodies and as labelled compounds in RIA and ELISA assays and as diagnostic or analytical aids in neurotransmitter research.
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- ACETYLENIC ALPHA-AMINO ACID-BASED SULFONAMIDE HYDROXAMIC ACID TACE INHIBITORS
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Compound of the formula (B) are useful in treating disease conditions mediated by TNF- alpha , such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.
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- Sulfonyl derivatives
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Sulfonyl derivatives represented by general formula (I), salts of the same, and solvates of both: and application of them as drugs: [wherein R1is hydrogen, hydroxyl, nitro or the like; R2and R3are each independently hydrogen, halogeno or the like; R4and R5are each dependently hydrogen, halogeno or the like; Q1is an optionally substituted saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group or the like; Q2is a single bond, oxygen or the like; Q3is, e.g., a group represented by formula (a): T1is carbonyl or the like; and X1and X2are each independently methylidyne or nitrogen]. These compounds exhibit potent Fxa inhibiting activities and serve as excellent anticoagulants which speedily exert satisfactory and persistent anti-thrombotic effects through oral administration and little cause adverse effects.
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- Aminoquinazolines and their use as medicaments
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Compounds of the formula having an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and air-ways, and the preparation thereof
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- NOVEL SULFONYL DERIVATIVES
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Sulfonyl derivatives represented by the following general formula (I): Q1-Q2-T1-Q3-SO2-QA and drugs containing the same (wherein Q1 is an optionally substituted, saturated or unsaturated, five- or six-membered cyclic hydrocarbon group, a five- or six-membered heterocyclic group, or the like; Q2 is a single band, oxygen, sulfur, C1-C6 alkylene or the like; QA is optionally substituted arylalkenyl, heteroarylalkenyl or the like; and T1 is carbonyl or the like). These compounds have potent FXa-inhibitory effects and promptly exert satisfactory and persistent antithrombotic effects through oral administration, thus being useful as anticoagulant agents little accompanied with side effects.
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- Process and intermediates for growth hormone secretagogues
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This invention relates to a process for preparing compounds of the Formula I, wherein R1, R2and Pt are as defined in the specification, which are intermediates in the synthesis of certain growth hormone secretagogue compounds. This invention further relates to processes for preparing the growth hormone secretagogues. The invention also relates to the compound of Formula I wherein R1is H, R2is 2,2,2-trifluoromethyl and Pt is Boc.
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- Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them
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Bicyclic heterocycles of general formula wherein: Ra to Rd, A to C and X are as defined herein, the tautomers, the stereoisomers and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, diseases of the lungs and respiratory tract, and the preparation thereof.
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