- Modular click chemistry libraries for functional screens using a diazotizing reagent
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Click chemistry is a concept in which modular synthesis is used to rapidly find new molecules with desirable properties1. Copper(i)-catalysed azide–alkyne cycloaddition (CuAAC) triazole annulation and sulfur(vi) fluoride exchange (SuFEx) catalysis are widely regarded as click reactions2–4, providing rapid access to their products in yields approaching 100% while being largely orthogonal to other reactions. However, in the case of CuAAC reactions, the availability of azide reagents is limited owing to their potential toxicity and the risk of explosion involved in their preparation. Here we report another reaction to add to the click reaction family: the formation of azides from primary amines, one of the most abundant functional groups5. The reaction uses just one equivalent of a simple diazotizing species, fluorosulfuryl azide6–11 (FSO2N3), and enables the preparation of over 1,200 azides on 96-well plates in a safe and practical manner. This reliable transformation is a powerful tool for the CuAAC triazole annulation, the most widely used click reaction at present. This method greatly expands the number of accessible azides and 1,2,3-triazoles and, given the ubiquity of the CuAAC reaction, it should find application in organic synthesis, medicinal chemistry, chemical biology and materials science.
- Meng, Genyi,Guo, Taijie,Ma, Tiancheng,Zhang, Jiong,Shen, Yucheng,Sharpless, Karl Barry,Dong, Jiajia
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- DIHYDROPYRIDINE COMPOUNDS HAVING SIMULTANEOUS ABILITY TO BLOCK L-TYPE CALCIUM CHANNELS AND TO INHIBIT PHOSPHODIESTERASE TYPE 3 ACTIVITY
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The present invention provides compounds that possess inhibitory activity against PDE-3 and L-type calcium channels. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating cardiovascular disease, stroke, epilepsy, ophthalmic disorder or migraine.
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- Dihydropyridines
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Dihydropyridine anti-ischaemic agents of the formula: STR1 and their salts where R is aryl or heteroaryl, R1 and R2 are each C1 -C4 alkyl or 2-methoxyethyl, Y is --(CH2)n -- where n is 2, 3, or 4 and is optionally substituted by 1 or 2 CH3 groups, and R3 is an optionally substituted 5- or 6-membered heterocyclic group attached to the adjacent N atom by a C atom, said group R3 being optionally fused to a further heterocyclic group or to a benzene ring.
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- 2-(SECONDARY AMINOALKOXYMETHYL) DIHYDROPYRIDINE DERIVATIVES AS ANTI-ISCHAEMIC AND ANTIHYPERTENSIVE AGENTS
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A dihydropyridine compound of the formula or a pharmaceutically acceptable acid addition salt thereof, wherein Y is -(CH2)2-, -(CH2)3-, -CH2CH(CH3)-or -CH2C(CH3)2-; R is aryl or heteroaryl; R1 and R2 are each independently C1-C4 alkyl or 2-methoxyethyl; and R3 is hydrogen, C1-C4 alkyl, 2-(Ci-C4 alkoxy)ethyl, cyclopropylmethyl, benzyl, or -(CH2)mCOR4 where m is 1, 2 or 3 and R4 is hydroxy, C1-C4 alkoxy or -NR5R6 where R5 and R6 are each independently hydrogen or C1-C4 alkyl can be employed for treating or preventing a heart condition or hypertension.
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- Dihydropyridine anti-ischaemic and antihypertensive agents
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1,4-Dihydropyridine derivatives of the formula: STR1 wherein R is aryl or heteroaryl: R1 and R2 are each independently C1 -C4 alkyl or 2-methoxyethyl; Y is --(CH2)n --, --CH2 CH(CH3)-- or --CH2 C(CH3)2 --; n is 1 to 3; and X is a 5 or 6 membered nitrogen containing aromatic heterocyclic ring which may optionally be substituted by one or more C1 -C4 alkyl, phenyl, benzyl, CN, --N(R3)2, (CH2)m CO2 H, (CH2)m CO2 (C1 -C4 alkyl) or (CH2)m CON(R3)2 group wherein each R3 is independently H or C1 -C4 alkyl and m is 0 or 1; and their pharmaceutically acceptable acid addition salts, and pharmaceutical preparation containing such compounds, have utility as anti-ischaemic and antihypertensive agents.
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- Dihydropyridine anti-ischaemic and antihypertensive agents
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1,4-Dihydropyridine derivatives of the formula: STR1 wherein R is aryl or heteroaryl; R1 and R2 are each independently C1 -C4 alkyl or 2-methoxyethyl; Y is --(CH2)n --, --CH2 CH(CH3)-- or --CH2 C(CH3)2 13 ; n is 1 to 3; and X is a 5 or 6 membered nitrogen containing aromatic heterocyclic ring which may optionally be substituted by one or more C1 -C4 alkyl, phenyl, benzyl, CN, --N(R3)2, (CH2)m CO2 H, (CH2)m CO2 (C1 -C4 alkyl) or (CH2)m CON(R3)2 group wherein each R3 is independently H or C1 -C4 alkyl and m is 0 or 1; and their pharmaceutically acceptable acid addition salts, and pharmaceutical preparation containing such compounds, have utility as anti-ischaemic and antihypertensive agents.
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