- Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair
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The enzyme 15-prostaglandin dehydrogenase (15-PGDH) catalyzes the first step in the degradation of prostaglandins including PGE2. It is a negative regulator of tissue repair and regeneration in multiple organs. Accordingly, inhibitors of 15-PGDH are anticipated to elevate in vivo levels of PGE2 and to promote healing and tissue regeneration. The small molecule SW033291 (1) inhibits 15-PGDH with Ki = 0.1 nM in vitro, doubles PGE2 levels in vivo, and shows efficacy in mouse models of recovery from bone marrow transplantation, ulcerative colitis, and partial hepatectomy. Here we describe optimized variants of 1 with improved solubility, druglike properties, and in vivo activity.
- Antczak, Monika I.,Zhang, Yongyou,Wang, Changguang,Doran, Jennifer,Naidoo, Jacinth,Voruganti, Sukesh,Williams, Noelle S.,Markowitz, Sanford D.,Ready, Joseph M.
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p. 3979 - 4001
(2017/05/19)
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- COMPOSITIONS AND METHODS OF MODULATING 15-PGDH ACTIVITY
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Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors and 15-PGDH activators described herein.
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Paragraph 00310
(2013/11/05)
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- Synthesis of Pyrimidine Derivatives Having Oxo, Thioxo or Amino Functions at Position 4 from 1,2,4-Dithiazolium Salts
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The (thioaroylamido)acrylonitriles 2, obtained by reaction of 1,2,4-dithiazolium salts 1 with ethyl cyanacetate, undergo ring tranformation reactions by reaction with ammonium acetate, primary and secondary amines and form the pyrimidines 7-9.A possible mechanism for these reactions is discussed.
- Briel, Detlef
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p. 345 - 348
(2007/10/02)
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- Synthesis of Heterocyclic Compounds. XXXIX. Synthesis of 5-Cyano-2-phenyl-4-thioxo-3,4-dihydropyrimidines
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The reaction of thiobenzamide with 3-alkoxy-3-aryl(or alkyl)-2-cyanopropenenitriles 1 and sodium 2-propoxide in 2-propanol afforded after acidic treatment 6-aryl(or alkyl)-5-cyano-2-phenyl-4-thioxo-3,4-dihydropyrimidines 3 through formation of the 3-aryl(
- Lorente, A.,Navio, J. L. Garcia,Vaquero, J. J.,Soto, J. L.
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- The Reaction of 3,5-Diphenyl-1,2,4-dithiazol-1-ium Perchlorate with Active Methylene Compounds
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The reaction of 3,5-diphenyl-1,2,4-dithiazol-1-ium perchlorate with several kinds of active methylenes gives a number of heterocycles, such as 4-hydroxy and 4-mercaptopyrimidine, pyrimidinone, and thiazole derivatives.On treatment with hydroxylamine-O-sulfonic acid, the 4-mercaptopyrimidines lead to the aminothio compounds or the isothiazolopyrimidine.
- Shibuya, Isao
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p. 605 - 606
(2007/10/02)
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- The Reaction of 2,4,6-Triphenyl-1,3,5-thiadiazin-1-ium Salt with Active Methylene Compounds
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The reaction of 2,4,6-triphenyl-1,3,5-thiadiazin-1-ium tetrafluoroborate with several active methylene compounds was studied.Nitromethane and nitroethane gave 2H-1,3,5-thiadiazines.The compounds possessing a benzoyl group reacted with this salt to give 5-
- Shibuya, Isao
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p. 2158 - 2160
(2007/10/02)
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