- Cationic lipid-conjugated hydrocortisone as selective antitumor agent
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Hydrocortisone, the endogenously expressed steroidal, hormonal ligand for glucocorticoid receptor (GR), is body's natural anti-inflammatory and xenobiotic metabolizing agent. It has both palliative as well as adverse effects in different cancer patients. Herein, we show that conjugation product of C16-carbon chain-associated cationic lipid and hydrocortisone (namely, HYC16) induces selective toxicity in cancer (e.g. melanoma, breast cancer and lung adenocarcinoma) cells with least toxicity in normal cells, through induction of apoptosis and cell cycle arrest at G2/M phase. Further, significant tumor growth inhibition was observed in syngeneic melanoma tumor model with considerable induction of apoptosis in tumor-associated cells. In contrast to hydrocortisone, significantly higher anti-angiogenic behavior of HYC16 helped in effective tumor shrinkage. This is the first demonstration to convert natural hormone hydrocortisone into a selective bioactive entity possessing anti-tumor effect.
- Rathore, Bhowmira,Chandra Sekhar Jaggarapu, Madhan Mohan,Ganguly, Anirban,Reddy Rachamalla, Hari Krishna,Banerjee, Rajkumar
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- Raw synthesis and mitochondrial function postischemic mitochondria diseases related to the lack or for use in new compd. 11β-hydroxysteroid
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The present invention provides novel compounds of 112-hydroxy steroids and compositions and their application as pharmaceuticals for preventing or reversing injury to mitochondria, for treating or preventing diseases relating to mitochondrial dysfunction or depletion, and for inducing regeneration or restructuring of mitochondria as a means of treating diseases relating to abnormalities in mitochondrial structure and function in a human or animal subject. Also disclosed herein are methods for diagnosing injury to mitochondria and for diagnosing the success or failure of therapeutics designed to treat, prevent, or reverse injury to or depletion of mitochondria.
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Paragraph 0274
(2016/10/08)
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- HIGHLY POTENT GLUCOCORTICOIDS
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The present invention relates to novel glucocorticoid compounds. The invention also relates to methods of using these compounds, the synthesis of these compounds, and to compositions and formulations comprising the glucocorticoid compounds, and uses thereof.
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Paragraph 0203; 0204; 0241; 0242
(2015/04/15)
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- Macrolactonolides: A novel class of anti-inflammatory compounds
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A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats. The synthesis, in vitro and in vivo anti-inflammatory activity of this novel class of compounds are described.
- Toma?kovi?, Linda,Komac, Marijana,Makaruha Stegi?, Oresta,Muni?, Vesna,Rali?, Jovica,Stani?, Barbara,Banjanac, Mihailo,Markovi?, Stribor,Hrva?i?, Bo?ka,?ip?i? Paljetak, Hana,Padovan, Jasna,Glojnari?, Ines,Erakovi? Haber, Vesna,Mesi?, Milan,Mer?ep, Mladen
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p. 321 - 332
(2013/02/23)
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- NITROXY DERIVATIVES OF SOFT STEROIDS
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A compound of formula (I) or a pharmaceutically acceptable salt thereof, and an ophthalmic composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. The invention is also directed to the use of the ophthalmic compositions for treating inflammatory conditions of the palpebral or bulbar conjunctiva, cornea and anterior segment of the globe, and to ameliorate inflammation associated with corneal injury.
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Page/Page column 15; 16
(2013/09/26)
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- NOVEL AMIDE COMPOUNDS
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The present invention provides compounds of formula (I) wherein n, R1, R2, X1, X2, X3, X4, X5, R3a, R3b, R4, R5 and R6 are
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Page/Page column 15
(2010/10/19)
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- NOVEL COMPOUNDS
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The present invention provides named compounds of formula (I) and pharmaceutical compositions containing them and their use in therapy.
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Page/Page column 21
(2010/10/19)
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- STEROIDAL [3, 2-C] PYRAZOLE COMPOUNDS, WITH GLUCOCORTICOID ACTIVITY
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The present invention provides compounds of formula (I) wherein n, p, R1, R2, X1, X2, X3, X4, X5, R3a, R3b, R4, R5 and R6 are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them and their use in therapy.
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Page/Page column 79
(2009/05/29)
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- Etiprednol dicloacetate, a new soft glucocorticoid drug candidate. Development of chemistry
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During development of chemistry of the soft drug candidate etiprednol dicloacetate (BNP-166) 1) optimization studies on the three-step chemical synthesis resulted in a process that could be scaled-up to the kg level, 2) the impurity profile was determined, 3) synthetic routes were developed for the preparation of the radiolabeled target compound, and 4) a series of hydroxylated metabolites was prepared.
- Csanadi,Horvath,Szekeres,Hasko,Ila,Ivanics,Patthy,Salat,Seres,Pallagi,Toth,Szederkenyi,Konya,Tegdes,Bodor,Zubovics, Zoltan
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p. 349 - 359
(2007/10/03)
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- Soft drugs based on hydrocortisone: The inactive metabolite approach and its application to steroidal antiinflammatory agents
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Purpose. The soft drug approach was applied to the design of analogs of highly potent synthetic steroids but with a metabolically labile ester group which at the same time served as an activating group. Methods. Several structural modifications of soft antiinflammatory steroids were synthesized and tested in several assays of biological activity. The hydrolytic stability of the compounds was also determined. Results. One of the compounds synthesized was determined to be a very potent steroid and had a highly significant separation of topical from systemic activity. However, the compound demonstrated greater than expected stability in the hydrolysis studies. Conclusions. The goal of the soft drug approach has been achieved with the development of a highly potent drug which displays little or no systemic activity as measured in the tests presented here. The anticipated hydrolytic instability of the compounds was not corroborated; however, in view of other results, the interpretation is allowed that the rapid hydrolysis of the unbound fraction of the drug is an important factor in its lack of systemic effects.
- Little, Roy J.,Bodor, Nicholas,Loftsson, Thorsteinn
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p. 961 - 967
(2007/10/03)
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- SOFT STEROIDS HAVING ANTI-INFLAMMATORY ACTIVITY
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Novel soft steroid anti-inflammatory agents, said agents being esters or thioesters of 17α-alkoxy-11β--hydroxyan-drost-4-en-3-one-17β-carboxylic acids, pharmaceutical compositions containing said agents, novel chemical intermediates useful in the preparation of said agents and methods of administering same to mammals in the treatment of inflammation. Preferred compounds are the haloalkyl esters of 17α-alkoxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylic acids.
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- Soft steroids having anti-inflammatory activity
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Novel soft steroid anti-inflammatory agents, said agents being esters or thioesters of 17α-alkoxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylic acids, pharmaceutical compositions containing said agents, novel chemical intermediates useful in the preparation of said agents and methods of administering same to mammals in the treatment of inflammation. Preferred compounds are the haloalkyl esters of 17α-alkoxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylic acids.
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- 17-KETOSTEROIDS VIA A BASE INDUCED CLEAVAGE OF C-17-DIHYDROXY ACETONE SIDE CHAINS
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A new, base-catalyzed cleavage of C21-steroids to give 17-ketosteroids is described.This reaction is specific for those steroids containing the C-17-dihydroxy acetone side chain.In the presence of oxygen, these same reaction conditions readily degrade corticosterone to the 17β-carboxylic acid.
- Simons, S. Stoney,Merchlinsky, Michael J.,Johnson, David F.
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p. 281 - 290
(2007/10/02)
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