Patent | Submitted | Granted |
---|---|---|
COMPOUNDS AND METHODS FOR TREATING INFLAMMATORY AND FIBROTIC DISORDERS [US2009318455] | 2009-12-24 | |
COMPOSITION AND METHOD FOR TREATING PROTEINURIA [US2010099719] | 2010-04-22 | |
COMPOSITION AND METHOD FOR TREATING FIBROTIC DISEASES [US2009258911] | 2009-10-15 | |
Composition and Method for Treating Fibrotic Diseases [US2008319027] | 2008-12-25 | |
METHODS FOR TREATING ACUTE MYOCARDIAL INFARCTIONS AND ASSOCIATED DISORDERS [US2010190731] | 2010-07-29 | |
Methods for Treating Acute Myocardial Infarctions and Associated Disorders [US2011218515] | 2011-09-08 | |
METHODS OF TREATING HIV PATIENTS WITH ANTI-FIBROTICS [US2012014917] | 2012-01-19 | |
Composition and Method for Treating Fibrotic Diseases Composition and Method for Treating Fibrotic Diseases [US2009005424] | 2007-08-30 | |
Crystalline 1-(3-fluorophenyl)-5-methyl-2-(1H)pyridone, the preparation methods, compositions and applications thereof [US8232408] | 2009-03-10 | 2012-07-31 |
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Tianagliflozin IND filed by Tianjin Institute of Pharmaceutical research
Tianagliflozin,
taigeliejing, 6-deoxydapagliflozin
Molecular Formula: | C21H25ClO5 |
---|---|
Molecular Weight: | 392.8732 g/mol |
IND Filing…Tianjin Institute of Pharmaceutical research
Tianjin Institute Of Pharmaceutical Research,
(3R,4S,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methyloxane-3,4,5-triol
1-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-1,6-dideoxy-b-D-glucopyranose
D-Glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-deoxy-, (1S)-
1–[4–Chloro–3–(4–ethoxybenzyl)phenyl]–1,6–dideoxy–β–d–glucopyranose
6-deoxydapagliflozin
A SGLT-2 inhibitor potentially for the treatment of type 2 diabetes.
CAS N. 1461750-27-5
The structures of dapagliflozin and 6-deoxydapagliflozin (1)
,deletion of the 6-OH in the sugar moiety of dapagliflozin led to the discovery of a more potent SGLT2 inhibitor, 6-deoxydapagliflozin (1, ). In an in vitro assay, 1 was a more active SGLT2 inhibitor, with IC 50 = 0.67 nM against human SGLT2 (hSGLT2), as compared with 1.1 nM for dapagliflozin, leading to the identification of 1 as the most active SGLT2 inhibitor discovered so far in this field. Also in an in vivo assay, 1 also introduced more urinary glucose in a rat urinary glucose excretion test (UGE) and exhibited more potent blood glucose inhibitory activity in a rat oral glucose tolerance test (OGTT) than dapagliflozin.
Given the fact that 6-dexoydapagliflozin (1) is a very promising SGLT2 inhibitor that could be used to treat type 2 diabetes, led to preclinical trials
Tianjin Institute Of Pharmaceutical Research,天津药物研究院
SPECTRAL DATA of Tianagliflozin
1 as a white solid (3.65 g, 93 %). R f = 0.35 (EtOAc);
m.p.: 148–149 °C;
1H NMR (400 MHz, DMSO-d 6): δ = 7.35 (d, 1H, J = 8.4 Hz), 7.25 (s, 1H), 7.18 (d, 1H, J = 8.0 Hz), 7.08 (d, 2H, J = 8.4 Hz), 6.81 (d, 2H, J = 8.4 Hz), 4.95 (d, 1H, J = 5.2 Hz, OH), 4.90 (d, 1H, J = 4.4 Hz, OH), 4.79 (d, 1H, J = 5.6 Hz, OH), 3.92–4.01 (m, 5H), 3.24–3.29 (m, 1H), 3.18–3.22 (m, 1H), 3.09–3.15 (m, 1H), 2.89–2.95 (m, 1H), 1.29 (t, 3H, J = 7.0 Hz, CH2 CH 3 ), 1.15 (d, 3H, J = 6.0 Hz, CHCH 3 ) ppm;
13C NMR (100 MHz, DMSO-d 6): δ = 156.85, 139.65, 137.82, 131.83, 131.16, 130.58, 129.52, 128.65, 127.14, 114.26, 80.71, 77.98, 75.77, 75.51, 74.81, 62.84, 37.55, 18.19, 14.62 ppm;
IR (KBr): v¯¯¯ = 3,564 (w), 3,385 (s), 2,981 (s), 2,899 (s), 2,861 (s), 1,613 (m), 1,512 (s), 1,477 (m), 1,247 (s), 1,102 (s), 1,045 (s), 1,012 (s) cm−1;
HR–MS: calcd for C21H29ClNO5 ([M + NH4]+) 410.1729, found 410.1724.
PATENT
CN 103864737
http://www.google.com/patents/CN103864737A?cl=en
PATENT
WO 2014094544
http://www.google.com/patents/WO2014094544A1?cl=en
-27-
1 D1 -6 Optionally, the step (7 ‘) is the step (7’) in place:
LS l- [4 – D (I- Dl- 6)
A.
(DMSO-d 6, 400 MHz), δ 7.35 (d, 1H, J = 8.0 Hz), 7.28 (d, 1H, J ‘. 2.0 Hz), 7.17 (dd, IH, / = 2.0 Hz and 8.4 Hz), 7.05 (d, 2H, J: 8.8 Hz), 6.79 (d, 2H, 8.8 Hz): 4.924,95 (m, 2H), 4,81 (d, IH, 6,0 Hz), 3.93- 3.99 (m, 5H), 3,85 (d, 1H, J = 10,4 Hz), 3,66 (dd, IH, 5,2 Hz and 11,6 Hz), 3.17-3,28 (m, 3H), 3.02-3.08 (m: IH), 1.28 (t, 3H, J = 7,0 Hz), 0,80 (s, 9H), -0.05 (s, 3H), -0.09 (s, 3H) .
PATENT
[0066] The added 100mL dried over anhydrous methanol 0. 5g of sodium metal, nitrogen at room temperature with stirring, until the sodium metal disappeared. Followed by addition of 5. 2g (10mmol) of compound 6, stirring was continued at room temperature for 3 hours. To the reaction system was added 5g strong acid cation exchange resin, stirred at room temperature overnight, the reaction mixture until pH = 7. The resin was removed by suction, and the filtrate evaporated to dryness on a rotary evaporator, the residue was further dried on a vacuum pump to give the product I-D1-6, as a white foamy solid.
PATENT
WO 2014139447
PATENT related
http://www.google.com/patents/WO2013044608A1?cl=en
http://link.springer.com/article/10.1007%2Fs40242-014-4043-9#/page-1
Med Chem. 2015;11(4):317-28.
Design of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: A History Driven by Biology to Chemistry.
Abstract
A brief history of the design of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors is reviewed. The design of O-glucoside SGLT2 inhibitors by structural modification of phlorizin, a naturally occurring O-glucoside, in the early stage was a process mainly driven by biology with anticipation of improving SGLT2/SGLT1 selectivity and increasing metabolic stability. Discovery of dapagliflozin, a pioneering C-glucoside SGLT2 inhibitor developed by Bristol-Myers Squibb, represents an important milestone in this history. In the second stage, the design of C-glycoside SGLT2 inhibitors by modifications of the aglycone and glucose moiety of dapagliflozin, an original structural template for almost all C-glycoside SGLT2 inhibitors, was mainly driven by synthetic organic chemistry due to the challenge of designing dapagliflozin derivatives that are patentable, biologically active and synthetically accessible. Structure-activity relationships (SAR) of the SGLT2 inhibitors are also discussed.
http://www.ncbi.nlm.nih.gov/pubmed/25557661
Paper

Discovery of 6-Deoxydapagliflozin as a Highly Potent Sodium-dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes
http://www.ingentaconnect.com/content/ben/mc/2014/00000010/00000003/art00009?crawler=true
CLIP
A facile synthesis of 6-deoxydapagliflozin
Keywords. Carbohydrates Drug research Hydrogenolysis Dapagliflozin SGLT2 inhibitor
The synthetic route to the target compound 1 is shown in Scheme 3. The starting material methyl 2,3,4-tri-O-benzyl-6-deoxy-6-iodo-α–d-glucopyranoside (3) was prepared from commercially available methyl α–d-glucopyranoside (2) according to a known method [5, 6].
Iodide 3 was reductively deiodinated to give 4 in 91 % yield under hydrogenolytic conditions using 10 % Pd/C as catalyst in the presence of Et3N as base in THF/MeOH at room temperature.
when the iodide 3 was treated with Barton–McCombie reagent (n-Bu3SnH/AIBN) [7] in toluene at room temperature no reaction occurred; however, when the reaction was carried out at elevated temperatures, such as reflux, a complex mixture formed with only a trace amount (3 %, entry 1) of the desired product 4.
When the iodide 3 was treated with LiAlH4 in THF at 0 °C to room temperature, another complex mixture was produced with only a trace amount (2 %, entry 2) of 4.
When Pd(OH)2 was used as the hydrogenolysis catalyst instead of 10 % Pd/C, the desired 4 was indeed formed (14 %, entry 4), but most of the starting material was converted to a few more polar byproducts, which were believed to result from the cleavage of at least one of the benzyl groups.
pdf available
Monatshefte für Chemie – Chemical Monthly
December 2013, Volume 144, Issue 12, pp 1903-1910
////////IND Filing, SGLT-2 inhibitor, type 2 diabetes, Tianagliflozin, taigeliejing, 6-deoxydapagliflozin, 1461750-27-5
Clc1c(cc(cc1)C2[C@@H]([C@H]([C@@H]([C@H](O2)C)O)O)O)Cc3ccc(cc3)OCC
CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)C3C(C(C(C(O3)C)O)O)O)Cl
c1(c(cc(cc1)C2OC(C(C(C2O)O)O)C)Cc3ccc(cc3)OCC)Cl
Fluorofenidone
Fluorofenidone
1- (3-fluorophenyl) -5-methyl – 2 (1H) pyridone
2(1H)-Pyridinone, 1-(3-fluorophenyl)-5-methyl-
1- (3_ fluorophenyl) -5_ methylpyridine _2 (IH) – one
C12 H10 F N O, 203.2123
PRECLINICAL, IND Filing
An anti-inflammatory agent potentially for the treatment of organ fibrosis.
CAS No. 848353-85-5
Synthesis
PATENT
WO 2006108354
http://www.google.co.in/patents/WO2006108354A1?cl=en
PATENT
http://www.google.com/patents/CN102241625A?cl=zh
(Compound 1)
A. (3_ fluorophenyl) methyl pyridine _2 (IH) 1- -5_ – -one
9. 6gDMF, 45 0g (0 2mol.) Inter-fluoro-iodobenzene, 21 8g (0. 2mol) 5_ methylpyridine _2_ (IH) -.. -one, 28g of anhydrous potassium carbonate and 1. Og copper powder, 160 ° -170 °, the reaction was stirred at reflux for 20 hours, the natural cooling to 110~120 ° C, was slowly added to about 330ml 80~90 ° C hot water, cooled to 20 ° C. Suction filtered, the filter cake was washed with about 20ml of water, remove the cake, with about 300ml of ethyl acetate ultrasound 30min, suction filtered, the filter residue was washed with 20ml of ethyl acetate. The combined ethyl acetate, washed with water three times (50ml * 3), and the filtrate layers were separated and allowed to stand for 15min, ethyl acetate fraction was concentrated to a non-steamed, hot added under stirring for about 85ml of petroleum ether, cooling to 15~20 ° C insulation ~ 1.5 hours. Filtration, the filter cake was washed twice with petroleum ether (about 20ml * 2) used to give 34. 9g crude. Recrystallized from 20% ethanol to give the product 1- (3_ fluorophenyl) -5_ methylpyridine _2 (IH) – one as a white solid # 30. Ig0 Μ P.: 132 · 1 ~133 7 °.. C.
PATENT
http://www.google.co.in/patents/WO2009149188A1?cl=zh-CN
PATENT
CN 102241625
http://www.google.com/patents/CN102241625A?cl=zh
PATENT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2009111947
PAPER
CN1386737A * | Jun 11, 2002 | Dec 25, 2002 | 中南大学湘雅医学院 | Antifibrosis pyridinone medicine and its prepaing process |
CN1846699A | Apr 13, 2005 | Oct 18, 2006 | 中南大学湘雅医院 | Application of 1-(substituted phenyl)-5-methyl-2-(1H)-pyridone compound in preparing medicine for anti-other organifibrosis and tissue fibrosis except renal interstitial fibrosis |
CN101235013A* | Mar 10, 2008 | Aug 6, 2008 | 广东东阳光药业有限公司;张中能 | Crystallized 1-(3-fluorophenyl)-5-methyl-2-(1H)pyridine and its preparation method composition and application |
US20070203203 | May 1, 2007 | Aug 30, 2007 | Tao Li J | Composition and Method for Treating Fibrotic Diseases |
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CC1=CN(C(=O)C=C1)C2=CC(=CC=C2)F