- Near-Infrared Photoswitching of Azobenzenes under Physiological Conditions
-
Biological tissue exhibits an absorbance minimum in the near-infrared between 700 and 900 nm that permits deep penetration of light. Molecules that undergo photoisomerization in this bio-optical window are highly desirable as core structures for the development of photopharmaceuticals and as components of chemical-biological tools. We report the systematic design, synthesis, and testing of an azobenzene derivative tailored to undergo single-photon photoswitching with near-infrared light under physiological conditions. A fused dioxane ring and a methoxy substituent were used to place oxygen atoms in all four ortho positions, as well as two meta positions, relative to the azobenzene N=N double bond. This substitution pattern, together with a para pyrrolidine group, raises the pKa of the molecule so that it is protonated at physiological pH and absorbs at wavelengths >700 nm. This azobenzene derivative, termed DOM-azo, is stable for months in neutral aqueous solutions, undergoes trans-to-cis photoswitching with 720 nm light, and thermally reverts to the stable trans isomer with a half-life near 1 s.
- Dong, Mingxin,Babalhavaeji, Amirhossein,Collins, Catherine V.,Jarrah, Kareem,Sadovski, Oleg,Dai, Qiuyun,Woolley, G. Andrew
-
-
Read Online
- CONDENSED HETEROCYCLIC COMPOUND HAVING 1,4-BENZO DIOXANE RING OR SALT THEREOF, AND ANTI-JUVENILE HORMONE AGENT COMPOSED OF THE COMPOUND
-
PROBLEM TO BE SOLVED: To provide a pest control agent containing a practical juvenile hormone antagonist activity compound as an active ingredient. SOLUTION: By using a reporter gene assay system that uses a juvenile hormone sequence, a heterocyclic compound having an antagonist activity is discovered, and a pest control agent containing the compound as an active ingredient is provided. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2020,JPOandINPIT
- -
-
Paragraph 0015; 0035
(2020/02/28)
-
- Methods of using diaminopyrimidine P2X3 and P2X2/3 receptor modulators for treatment of respiratory and gastrointestinal diseases
-
Methods for treating respiratory and gastrointestinal diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein D, X, Y, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein.
- -
-
Page/Page column 102
(2010/11/26)
-
- Diaminopyrimidines as P2X3 and P2X2/3 antagonists
-
Compounds and methods for treating diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein D, X, Y, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein.
- -
-
Page/Page column 114
(2010/02/14)
-
- Inhibitors of α4 mediated cell adhesion
-
The present invention relates to a pharmaceutical composition comprising as an active ingredient a compound of formula (I), wherein Ring A is an aromatic or a heterocyclic ring; Q is a bond, carbonyl, lower alkylene, lower alkenylene, —O-(lower alkylene)-, etc.; n is 0, 1 or 2; Z is oxygen or sulfur, W is oxygen, sulfur, —CH═CH—, —NH— or —N═CH—; R1, R2and R3are the same or different and are hydrogen, halogen, hydroxyl, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkoxy group, a substituted or unsubstituted amino group, etc.; R4is tetrazolyl, carboxyl group, amide or ester; R5is hydrogen, nitro, amino, hydroxyl, lower alkanoyl, lower alkyl etc.; R6is selected from (a) a substituted or unsubstituted phenyl group, (b) a substituted or unsubstituted pyridyl group, (c) a substituted or unsubstituted thienyl group, (d) a substituted or unsubstituted benzofuranyl group, etc.; or a pharmaceutically acceptable salt thereof.
- -
-
-
- Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: Discovery of TR-14035, a dual α4β7/α4β1 integrin antagonist
-
α4β1 and α4β7 integrins are key regulators of physiologic and pathologic responses in inflammation and autoimmune disease. The effectiveness of anti-integrin antibodies to attenuate a number of inflammatory/immune conditions provides a strong rationale to target integrins for drug development. Important advances have been made in identifying potent and selective candidates, peptides and peptidomimetics, for further development. Herein, we report the discovery of a series of novel N-benzoyl-L-biphenylalanine derivatives that are potent inhibitors of α4 integrins. The potency of the initial lead compound (1: IC50 α4β7/α4β1 =5/33 μM) was optimized via sequential manipulation of substituents to generate low nM, orally bioavailable dual α4β1/α4β7 antagonists. The SAR also led to the identification of several subnanomolar antagonists (134, 142, and 143). Compound 81 (TR-14035; IC50 α4β7/α4β1 =7/87 nM) has completed Phase I studies in Europe. The synthesis, SAR and biological evaluation of these compounds are described.
- Sircar, Ila,Gudmundsson, Kristjan S.,Martin, Richard,Liang, Jimmy,Nomura, Sumihiro,Jayakumar, Honnappa,Teegarden, Bradley R.,Nowlin, Dawn M.,Cardarelli, Pina M.,Mah, Jason R.,Connell, Samuel,Griffith, Ronald C.,Lazarides, Elias
-
p. 2051 - 2066
(2007/10/03)
-
- Substituted heterocyclic compounds, method for preparing and compositions containing same
-
The invention relates to compounds of formula (I): wherein: R1, R2and R3are as defined in the description, X is as defined in the description, Y represents an oxygen atom, a sulphur atom, a C(H)qgroup, SO or SO2, n is equal to from 0 to 5, A represents a NR5R6group, and medicinal products containing the same which are useful in treating or in preventing melatoninergic disorders.
- -
-
-
- Convenient synthesis of 5-substituted-6-methoxy or 6-hydroxy-2,3-dihydro-1,4-benzodioxins via lithiated intermediates
-
The 6-methoxy and 6-tetrahydropyranyloxy-2,3-dihydro-1,4-benzodioxins can be lithiated at the 5-position to give intermediate lithio derivatives which react with various electrophiles to afford, after hydrolysis, 5-substituted-6-methoxy and 6-hydroy-2,3-d
- Besson,Hretani,Coudert,Guillaumet
-
p. 1421 - 1430
(2007/10/02)
-
- Syntheses of 2-Substituted 6/7-Methoxy-1,4-benzodioxan-7/6-carbaldehydes
-
Five 2-substituted 6/7-methoxy-1,4-benzodioxan-7/6-carbaldehydes and 6-methoxy-1,4-benzodioxan-7-carbaldehyde available for the syntheses of insecticidal neolignan analogs were prepared from 4/3-benzyloxy-3/4-hydroxybenzaldehydes and 1,4-benzodioxan-6-carbaldehyde, respectively.
- Taniguchi, Eiji,Yamauchi, Satoshi,Nagata, Shyuichirou,Ohnishi, Takeshi
-
p. 630 - 635
(2007/10/02)
-
- Synthese et proprietes biologiques photoinduites de dioxinnocoumarines lineaires
-
Synthesis and photoinduced biological properties of linear dioxinocoumarins.Several dioxinocoumarins with a substituted or unsubstituted coumarin moiety were synthesized from commercially available 6-amino-1,4-benzodioxan.Qualitative assays on the photoinduced inhibition of growth in the yeast Saccharomyces cerevisiae indicate that two dioxinocoumarins are photobiologically active. The 5H- benzopyranobenzodioxin-5-one 1d is more active than angelicin but less active than 8-MOP.The 9-methyl-7H-pyranobenzodioxin-7-one 1c is slightly less active than angelicin.
- Guillaumet, Gerald,Hretani, Mohamed,Coudert, Gerard,Averbeck, Dietrich,Averbeck, Simone
-
-
- SYNTHESE D'UN ANALOGUE DIOXINIQUE DU PSORALENE
-
The synthesis of a new analog of psoralen built on a benzodioxinic moiety have been efficiently achieved using as a key intermediate the 6-hydroxy 7-formyl 1,4-benzodioxan.
- Guillaumet, G.,Hretani, M.,Coudert, G.
-
p. 2665 - 2666
(2007/10/02)
-