New Drug Approvals

Home » DIABETES » Henagliflozin

Henagliflozin

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

PAYPAL DONATIONS

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Categories

Blog Stats

  • 1,301,135 hits

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 1,773 other followers

add to any

Share

2D chemical structure of 1623804-44-3

Henagliflozin, SHR-3824 ,

CAS 1623804-44-3

C22-H24-Cl-F-O7

454.8756

PHASE 2 for the treatment of type 2 diabetes

HengRui (Originator)

Jiangsu Hengrui Medicine Co Ltd

UNII-21P2M98388; 21P2M98388; Henagliflozin; SHR3824; SHR-3824;

In April 2016, Jiangsu Hengrui Medicine is developing henagliflozin (phase 2 clinical trial), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, for treating type 2 diabetes. 

SGLT1 and SGLT2 inhibitors, useful for treating eg diabetes.

Henagliflozin proline is in phase II clinical trials by Jiangsu Hengrui (江苏恒瑞) for the treatment of type 2 diabetes.

1,6-dehydrated-1-C{4-chloro-3-[(3-fluoro-4-ethoxyphenyl)methyl]phenyl}-5-C-(hydroxymethyl)-β-L-idopyranose L-proline

(1 ^ 2345-5- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -1- (hydroxymethyl) 6,8 – alcohol dioxide

(1R,2S,3S,4R,5R)-5-[4-chloro-3-[(4-ethoxy-3-fluorophenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol

front page image

Shanghai Hengrui Pharmaceutical Co., Ltd., 上海恒瑞医药有限公司, Jiangsu Hengrui Medicine Co., Ltd., 江苏恒瑞医药股份有限公司, Less «

  • 01 May 2015 Jiangsu HengRui Medicine Co. initiates enrolment in a phase I drug interaction trial in volunteers in China (NCT02500485)
  • 12 Feb 2015 Jiangsu HengRui Medicine plans a phase I trial for Type-2 diabetes mellitus in China (NCT02366377)
  • 01 Feb 2015 Jiangsu HengRui Medicine initiates enrolment in a phase I trial for Type-2 diabetes mellitus in China (NCT02366351)

Henagliflozin is a novel sodium-glucose transporter 2 inhibitor and presents a complementary therapy to metformin for patients with T2DM due to its insulin-independent mechanism of action. This study evaluated the potential pharmacokinetic drug-drug interaction between henagliflozin and metformin in healthy Chinese male subjects. 2. In open-label, single-center, single-arm, two-period, three-treatment self-control study, 12 subjects received 25 mg henagliflozin, 1000 mg metformin or the combination. Lack of PK interaction was defined as the ratio of geometric means and 90% confidence interval (CI) for combination: monotherapy being within the range of 0.80-1.25. 3. Co-administration of henagliflozin with metformin had no effect on henagliflozin area under the plasma concentration-time curve (AUC0-24) (GRM: 1.08; CI: 1.05, 1.10) and peak plasma concentration (Cmax) (GRM: 0.99; CI: 0.92, 1.07). Reciprocally, co-administration of metformin with henagliflozin had no clinically significant on metformin AUC0-24 (GRM: 1.09, CI: 1.02, 1.16) although there was an 11% increase in metformin Cmax (GRM 1.12; CI 1.02, 1.23). All monotherapies and combination therapy were well tolerated. 4. Henagliflozin can be co-administered with metformin without dose adjustment of either drug.

PATENT

WO-2016050134

With the improvement of socio-economic development and living standards, worldwide rapid growth of diabetes, diabetes is usually divided into two kinds of diabetes type Ⅰ and type Ⅱ diabetes, more than 90% of type Ⅱ diabetes. Species has been listed diabetes drugs a lot, but so far, no drugs which can single-handedly blood glucose levels in patients with type Ⅱ diabetes in the long-term target range. In recent years, in-depth study of the pathogenesis of diabetes, for the treatment of type Ⅱ diabetes provide more and more ways, and sodium – glucose cotransporter 2 (sodium-glucose transporter 2, SGLT-2) inhibitors found for treatment of diabetes provides another new idea. SGLT-2 inhibitors in the treatment mechanism of inhibition of SGLT-2 activity by selective to lower blood sugar. Select the SGLT-2 as a target, partly because of its absolute weight of glucose absorption, and partly because it is only expressed in the kidney. The current study also found that the mechanism of SGLT-2 does not depend on the degree of abnormal function of β cells or insulin resistance, its effect is not as severe failure or insulin resistance and β-cell function decline.Therefore, it is reasonable that the SGLT-2 inhibitors for the treatment of type Ⅱ diabetes currently has good prospects.

 

WO2012019496 discloses SGLT-2 inhibitor of the following formula, and its chemical name is 1,6-anhydro -1-C- {4- chloro-3 – [(3-fluoro-4-ethoxyphenyl) methyl] phenyl} -5-C- (hydroxymethyl) -β-L- idose pyranose.

 

However, direct 1,6-anhydro -1-C- {4- chloro-3 – [(3-fluoro-4-ethoxyphenyl) methyl] phenyl} -5-C- (hydroxymethyl) – β-L- idose pyranose as a pharmaceutically active ingredient is not realistic, because a lower melting point (83 ℃), having a hygroscopicity, poor development of the form, therefore, to develop it into a stable form of the compound having the transformation very important.
Example 1
Take (1.0g, 2.2mmol) 1,6- dehydration -1-C- {4- chloro-3 – [(3-fluoro-4-ethoxyphenyl) methyl] phenyl} -5-C- ( hydroxymethyl) -β-L- Aidoo pyranose (prepared by the method disclosed in WO2012019496), in 7.20g ethanol addition was completed, stirring to dissolve. Was added at room temperature L- proline (0.2786g, 2.42mmol, 1.1eq), the addition was completed, the reaction was warmed at reflux for 10min, the reaction solution was clear, hot filtered and the filtrate was stirred to room temperature, there is a lot of white solid precipitated , allowed to stand overnight, filtered, and dried, to give the formula (I), compound as a white solid 1.14 g, yield 88%. X- ray diffraction spectrum of the crystalline sample is shown in Figure 1. The crystallization at about 5.41 (16.33) 7.69 (11.49), 10.22 (8.65) 12.04 (7.35), 12.46 (7.10), 14.42 (6.14), 17.30 (5.12), 18.79 (4.72), 19.38 (4.58), 20.24 (4.38), 22.73 (3.91), 24.58 (3.62), 27.55 (3.24), 28.82 (3.10) and 31.03 (2.88) at the characteristic peaks. DSC spectrum shown in Figure 2, has a melting endothermic peak 111.20 ℃, this is defined as a Form A polymorph.

 

 

PATENT

WO2012019496

https://www.google.com/patents/WO2012019496A1?cl=en

Example 4

(1 ^ 2345-5- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -1- (hydroxymethyl) 6,8 – alcohol dioxide

Figure imgf000031_0001
Figure imgf000032_0001

first step

1-ethoxy-2-fluoro – benzene

A mixture of 2-fluoro-phenol 4a (6.7 g, 60 mmol) was dissolved in 66 mL of acetone, was added iodoethane (6.3 mL,

78 mmol) and potassium carbonate (12.4 g, 90 mmol), at reflux in an oil bath for 5 hours. The reaction solution was concentrated under reduced pressure, was added 100 mL of ethyl acetate and 60 mL of water, separated, the aqueous phase was extracted with ethyl acetate (30 mLx2), the organic phases combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure, to give the title product 1-ethoxy-2-fluoro – benzene 4b (6.9 g, red oil). yield: 82.1%.

MS m / z (ESI): 280.2 [2M + 1]

The second step

(5-bromo-2-chloro – phenyl) – (4-ethoxy-3-fluoro-phenyl) – methanone A mixture of 5-bromo-2-chloro – benzoyl chloride 2a (12.4 g, 48.8 mmol) was dissolved a 100 mL of dichloromethane was added 1-ethoxy-2-fluoro – benzene 4b (6.84 g, 48.8 mmol), cooled to 0 ° C, was added portionwise aluminum (5.86 g, 44 mmol) chloride, 16 h. Was added dropwise under ice-cooling to the reaction mixture 20 mL of 2 M HCl solution, separated, the aqueous phase was extracted with 30 mL of dichloromethane, and the combined organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the title The product (5-bromo-2-chloro – phenyl) – (4-ethoxy-3-fluoro-phenyl) – methanone 4c (12.7 g, yellow solid), yield: 72.6%.

MS m / z (ESI): 358.9 [M + l] Step

(5 – bromo-2-chloro – phenyl) – (4-ethoxy-3-fluoro-phenyl) – methanol (5-Bromo-2-chloro – phenyl) – (4-ethoxy -3 – fluoro – phenyl) -methanone 4c (12.7 g, 35.5 mmol) was dissolved in methanol and a 100 mL of tetrahydrofuran (ν: ν = 1: 1) mixed solvent, under an ice bath was added portionwise sodium borohydride (2.68 g, 70 mmol), and reacted at room temperature for 30 minutes. Add 15 mL of acetone, the reaction solution was concentrated under reduced pressure, 150 mL of ethyl acetate was added to dissolve the residue, washed with saturated sodium chloride solution (50 mLx2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure The filtrate, to give the title product (5-bromo-2-chloro – phenyl) – (4-ethoxy-3-fluoro-phenyl) – methanol 4d (12.7 g, orange oil), was used directly without isolation next reaction.

the fourth step

4 – [(5-bromo-2-chloro-phenyl) – methyl] Small-ethoxy-2-fluoro – benzene (5-bromo-2-chloro – phenyl) – (4-ethoxy -3 – fluoro – phenyl) methanol 4d (12.7 g, 35.3 mmol) was dissolved in a 100 mL of dichloromethane was added triethylsilane (16.9 mL, 106 mmol), was added dropwise boron trifluoride etherate (8.95 mL, 70.6 mmol ), for 3 hours. Was added 50 mL of saturated sodium bicarbonate solution, separated, the aqueous phase was extracted with ethyl acetate (100 mLx2), the organic phases combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure, purified by silica gel column chromatography to elute B surfactant system resulting residue was purified to give the title product 4 – [(5-bromo-2-chloro – phenyl) methyl] -1-ethoxy-2-fluoro – benzene 4e (10 g, as a pale yellow oil ) yield: 82.4%.

1H NMR (400 MHz, CDC1 3 ): δ 7.33-7.27 (m, 3H), 6.95-6.90 (m, 3H), 4.14 (q, 2H), 4.01 (s, 2H), 1.49 (t, 3H)

the fifth step

(2 3R, 4S, 5 ^ 6R) -2- [4- chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -6- (hydroxymethyl) – 2-methoxy – tetrahydro-pyran-3,4,5-triol

4 – [(5-bromo-2-chloro – phenyl) methyl] -1-ethoxy-2-fluoro – benzene 4e (7.36 g, 21.4 mmol) was dissolved in 30 mL of tetrahydrofuran, cooled to -78 ° C, was added dropwise a solution of n-butyllithium in hexane (10.27 mL, 25.7 mmol), at -78 ° C to react 1 hour, a solution of 20 mL (3R, 4S, 5R, 6R) -3,4,5 – tris (trimethylsilyloxy) -6- (trimethylsilyloxy) tetrahydropyran-2-one 2f (llg, 23.6 mmol) in tetrahydrofuran at -78 ° C under reaction 2 h, 2.8 mL of methanesulfonic acid and 71 mL of methanol, the reaction at room temperature for 16 hours. Was added 100 mL of saturated sodium carbonate solution, the reaction solution was concentrated under reduced pressure, to the residue was added 50 mL of saturated sodium chloride solution, extracted with ethyl acetate (100 mLx3), organic phases were combined, dried over anhydrous magnesium sulfate, filtered, The filtrate was concentrated under reduced pressure, purified by silica gel column chromatography with eluent systems resulting A residue was purified to give the title product (2 3R, 4S, 5 6R) -2- [4- chloro-3 – [(4-ethoxyphenyl 3-fluoro-phenyl) – methyl] phenyl] -6- (hydroxymethyl) -2-methoxy – tetrahydro-pyran-3,4,5-triol 4f (5.7 g, white solid ) yield: 58.3%.

1H NMR (400 MHz, CD 3 OD): δ 7.56 (s, 1H), 7.48 (dd, 1H), 7.37 (dd, 1H), 6.95-6.87 (m, 3H), 4.08-4.07 (m, 4H) , 3.91 (m, 1H), 3.93-3.73 (m, 2H), 3.56-3.53 (m, 1H), 3.45-3.43 (m, 1H), 3.30 (s, 2H), 3.08 (s, 3H), 1.35 (t, 3H)

The sixth step

(2 3R, 4S, 5 6R) -6- [(tert-butyl (dimethyl) silyl) oxymethyl] -2- [4-chloro-3 – [(4-ethoxy-3-fluoro – phenyl) methyl] phenyl] -2-methoxy – tetrahydro-pyran-3,4,5-triol the (2 3R, 4S, 5 6R) -2- [4- chloro-3- [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -6- (hydroxymethyl) -2-methoxy – 4f tetrahydropyran-3,4,5-triol (5.7 g, 12.5 mmol) was dissolved in 50 mL of pyridine, followed by adding tert-butyldimethylsilyl chloride (2.26 g, 15 mmol) and 4-dimethylaminopyridine (305 mg, 2.5 mmol), for 16 hours. The reaction solution was concentrated under reduced pressure, was added 200 mL of ethyl acetate, washed with a saturated copper sulfate solution (50 mLx3). The combined organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the title product (2 3R, 4S, 5 6R) -6- [(tert-butyl (dimethyl) silyl) oxymethyl] -2- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -2-methoxy – tetrahydro-pyran-3,4,5-triol 4g (7.14 g, colorless oil), without isolation directly used for the next reaction.

Seventh Step

[[(2R, 3R, 4S, 5R, 6 ^ -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl yl] phenyl] -6-methoxy – tetrahydropyran-2-yl] methoxy] – tert-butyl – dimethyl-silane (2 3R, 4S, 5 6R) -6- [(tert butyl (dimethyl) silyl) oxymethyl] -2- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -2-methoxy yl – tetrahydro-pyran-3,4,5-triol 4g (7.14 g, 12.5 mmol) was dissolved in 100 mL N, N- dimethylformamide was added 60% sodium hydride under ice-cooling (2.5 g , 62.5 mmol), and reacted at room temperature for 40 minutes completed the opening force, was added benzyl bromide (7.5 mL, 62.5 mmol), reaction of 16 hours. 20 mL of methanol, the reaction solution was concentrated under reduced pressure, was added 200 mL of ethyl acetate and 50 mL of water to dissolve the residue, separated, the aqueous phase was extracted with ethyl acetate (50 mL), the organic phase was washed with water (50 mL), washed with saturated sodium chloride solution (50 mL), the combined organic phase was dried over anhydrous magnesium sulfate , filtered, and the filtrate was concentrated under reduced pressure to give the title product [[(2R, 3R, 4S, 5R, 6 ^ -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4- ethoxy-3-fluoro-phenyl) – methyl] phenyl] -6-methoxy – tetrahydropyran-2-yl] methoxy] – tert-butyl – dimethylsilane 4h (10.5 g , yellow oil) yield: 99.8%.

Step Eight

[(2R, 3R, 4S, 5R, 6 -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -6-methoxy – tetrahydropyran-2-yl] methanol

The [[(2R, 3R, 4S, 5R, 6 -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl yl] phenyl] -6-methoxy – tetrahydropyran-2-yl] methoxy] – tert-butyl – dimethylsilane 4h (10.52 g, 12.5 mmol) was dissolved in 50 mL of methanol dropwise add acetyl chloride CO.13 mL, 1.9 mmol), for 1 hour. The reaction solution was concentrated under reduced pressure, purified by silica gel column chromatography with eluent systems B resultant residue was purified to give the title product [(2R, 3R, 4S, 5R, 6 -3,4,5- tris-benzyloxy–6 – [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -6-methoxy – tetrahydropyran-2-yl] methanol 4i (7.6 g , yellow oil yield: 83.6%.

Step Nine

(2 ^ 3456 3,4,5-tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] – 6-methoxy – tetrahydropyran-2-carbaldehyde

Oxalyl chloride (1.17 mL, 13.6 mmol) was dissolved in 20 mL of dichloromethane, cooled to -78 ° C, were added dropwise 20 mL of dimethyl sulfoxide (1.56 mL, 21.9 mmol) in methylene chloride and 50 mL [(2R, 3R, 4S, 5R, 6 -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -6-methoxy – tetrahydropyran-2-yl] methanol 4i (7.6 g, 10.45 mmol) in methylene chloride, and reacted at -78 ° C for 30 min, triethylamine (7.25 mL, 52.3 mmol), 2 hours at room temperature was added 50 mL 1 M HCl solution, separated, the organic phase was washed with saturated sodium chloride solution (50 mL x 2), the aqueous phase was extracted with dichloromethane (50 mL), the combined organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the title product (2 ^ 3456 3,4,5-tris-benzyloxy-6- [4-chloro-3 – [(4 – ethoxy-3-fluoro-phenyl) – methyl] phenyl] -6-methoxy – tetrahydropyran-2-carbaldehyde 4j (7.58 g, colorless oil), was used directly without isolation next reaction.

The tenth step

(2S, 3 4S, 5R, 6 -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl ] -2- (hydroxymethyl) -6-methoxy – tetrahydropyran-2-carbaldehyde

The (23456 3,4,5-tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] – 6-methoxy – tetrahydropyran-2-carbaldehyde 4j (7.6 g, 10.45 mmol) was dissolved in 80 mL 1,4- dioxane, followed by adding 15.8 mL 37% aqueous formaldehyde and sodium hydroxide solution (31.35 mL, 31.35 mmol), reacted at 70 ° C for 16 h. Add 50 mL of saturated sodium chloride solution, extracted with ethyl acetate (50 mLx4), the organic phase was washed with saturated sodium bicarbonate solution (50 mL), washed with saturated sodium chloride solution (50 mL), the combined organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the title product (23,456 benzyloxy-3,4,5-tris – 6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -2- (hydroxymethyl) -6-methoxy – tetrahydropyran – 2- formaldehyde 4k (7.9g, as a colorless oil), without isolation directly used for the next reaction.

Step Eleven

[(3 4S, 5R, 6 -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] 2- (hydroxymethyl) -6-methoxy – tetrahydropyran-2-yl] methanol

The (23456 3,4,5-tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] – 2- (hydroxymethyl) -6-methoxy – tetrahydropyran-2-carbaldehyde 4k (7.9 g, 10.45 mmol) was dissolved in 50 mL of tetrahydrofuran and methanol (v: v = 2: 3) mixed solvent , was added sodium borohydride (794 mg, 20.9 mmol), for 30 minutes. Add a small amount of acetone, the reaction solution was concentrated under reduced pressure, purified by silica gel column chromatography with eluent systems resulting A residue was purified to give the title product, 5R, 6 -3,4,5-tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -2- (hydroxymethyl ) -6-methoxy – tetrahydropyran-2-yl] methanol 4m (l.ll g, colorless oil). yield: 14.1%.

Step Twelve

[(12345 ^ -2,3,4-tris-benzyloxy-5- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] 6,8-dioxa-bicyclo [3.2.1] octane-1-yl] methanol

The [(3S, 4S, 5R, 6 -3,4,5- tris-benzyloxy-6- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] benzene yl] -2- (hydroxymethyl) -6-methoxy – tetrahydropyran-2-yl] methanol 4m (l.ll g, 1.46 mmol) was dissolved in 20 mL of dichloromethane, cooled to -10 ° C, was added trifluoroacetic acid (0.23 mL, 3 mmol), and reacted at room temperature for 2 hours. 20 mL of saturated sodium bicarbonate solution, separated, the aqueous phase was extracted with dichloromethane (20 mL> <2), and the combined organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure, purified by silica gel column chromatography with eluent systems B resultant residue was purified to give the title product [(1 2 3 4R, 5 -2,3,4- tris-benzyloxy-5- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] 6,8-dioxa-bicyclo [3.2.1] octane-1-yl] methanol 4nC830 mg, colorless oil). yield: 78.3%.

MS m / z (ESI): 742.3 [M + 18]

Thirteenth Step

(12345-5- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -1- (hydroxymethyl) -6,8 dioxa-bicyclo [3.2.1] octane-2,3,4-triol

The [(1 2 3 4R, 5S) -2,3,4- tris-benzyloxy-5- [4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] benzene yl] -6,8-dioxa-bicyclo [3.2.1] octane-1-yl] methanol 4n (830 mg, 1.14 mmol) was dissolved in 20 mL of tetrahydrofuran and methanol (v: v = l: l) the a mixed solvent of o-dichlorobenzene was added (1.3 mL, 1 1.4 mmol) and Pd / C (500 mg, 10%), purged with hydrogen three times, the reaction for 3 hours. The reaction solution was filtered, rinsed with a small amount of ethyl acetate, the filtrate was concentrated under reduced pressure, purified by silica gel column chromatography with eluent systems resulting A residue was purified to give the title product (1S, 2 3S, 4R, 5 -5- [ 4-chloro-3 – [(4-ethoxy-3-fluoro-phenyl) – methyl] phenyl] -1- (hydroxymethyl) -6,8-dioxa-bicyclo [3.2.1] octane-2,3,4-triol 4 (420 mg, white solid), yield: 81.0% MS m / z (ESI):. 472.2 [m + 18]

1H NMR (400 MHz, CD 3 OD): δ 7.47 (s, 1H), 7.42-7.35 (m, 2H), 6.95-6.87 (m, 3H), 4.16-4.14 (m, 1H), 4.06-4.02 ( m, 4H), 3.85-3.70 (m, 2H), 3.67-3.54 (m, 4H), 1.37 (t, 3H)

UNII-21P2M98388.png

////////Henagliflozin, SHR-3824 , PHASE 2,  type 2 diabete,  UNII-21P2M98388,  21P2M98388,  SHR 3824,  SHR3824,

CCOc1ccc(cc1F)Cc2cc(ccc2Cl)[C@]34[C@@H]([C@H]([C@@H]([C@](O3)(CO4)CO)O)O)O


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Paypal Donate

DR ANTHONY CRASTO

Follow New Drug Approvals on WordPress.com

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 1,773 other followers

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 29 year tenure till date Aug 2016, Around 30 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 25 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 13 lakh plus views on New Drug Approvals Blog in 212 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

Personal Links

View Full Profile →

TWITTER

bloglovin

Follow my blog with Bloglovin The title of your home page You could put your verification ID in a comment Or, in its own meta tag Or, as one of your keywords Your content is here. The verification ID will NOT be detected if you put it here.
%d bloggers like this: