BEXICASERIN

 

Bexicaserin

https://newdrugapprovals.org/2025/04/15/bexicaserin/

UNITED ARAB EMIRATES UNIVERSITY NEW PATENT WO/2022/038578

 

WO/2022/038578

BIODEGRADGRADABLE DEVICES, AND METHODS OF MAKING THE SAME

UNITED ARAB EMIRATES UNIVERSITY

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022038578&_gid=202208

ApplicantsUNITED ARAB EMIRATES UNIVERSITY 

InventorsGALIWANGO, EmmanuelAL MARZOUQI, AliABU-JDAYIL, BasimCAIRES, YousufMOuSA noranHARIS, Sabeera

AgentsAL TAMIMI & COMPANY  bioplastic blend is disclosed. The bioplastic blend may comprise a polylactic acid polymer and a lignocellulosic biomass. The lignocellulosic biomass may be a particulate and have an average particle size that is less than or equal to 60 micrometers, or less than or equal to 50 micrometers. The lignocellulosic biomass may be a particulate and comprise greater than or equal to 50 percent by weight of the bioplastic blend, or greater than or equal to 60 percent by weight of the bioplastic blend. In addition, the bioplastic blend may comprise a plasticizer.

United Arab Emirates University

جامعة الإمارات العربية المتحدة
Type	Public
Established	1976; 46 years ago
Chancellor	Zaki Nusseibeh
Vice-Chancellor	Ghaleb Ali Al Hadrami Al Breiki
Provost	Mohammed Hassan Ali
Undergraduates	15,019
Postgraduates	676
Location	Al Ain ,  United Arab Emirates
Campus	Urban
Nickname	UAEU
Website	uaeu.ac.ae

link https://en.wikipedia.org/wiki/United_Arab_Emirates_University
United Arab Emirates University (UAEU; Arabic: جامعة الإمارات العربية المتحدة) is a public research university located in Al Ain, United Arab Emirates. It is the oldest university in the United Arab Emirates. It was established in 1976 after independence from Britain by the founding father of the UAE, the late Sheikh Zayed bin Sultan Al Nahyan.

WO/2021/205354 NOVEL NATURE-INSPIRED ANTICANCER AND ANTIBACTERIAL ... UNIV SHARJAH

 

WO2021205354 - NOVEL NATURE-INSPIRED ANTICANCER AND ANTIBACTERIAL MOTIFS AND PHARMACEUTICAL COMPOSITION THEREOF

WO/2021/205354

NOVEL NATURE-INSPIRED ANTICANCER AND ANTIBACTERIAL MOTIFS AND PHARMACEUTICAL COMPOSITION THEREOF

UNIVERSITY OF SHARJAH

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021205354&_cid=P12-KZJPKP-63707-1

ApplicantsUNIVERSITY OF SHARJAH 

InventorsALTEL, Taleb H.
here is provided novel anticancer and antibacterial compounds, pharmaceutically acceptable salts thereof, and processes for their preparation. The compounds have anticancer activity, which results in the reduction of tumour cell proliferation, enhances cancers cells apoptosis and regulation of iron signalling. The compounds are also particularly active against various Gram-negative and Gram-positive multidrug-resistant bacteria, such as extended-spectrum beta-lactamase (ESBL) producing and colistin-resistant Escherichia coli, carbapenem-resistant E. coli, carbapenem-resistant Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA) including those with reduced susceptibility to many control antibiotics.

WO2021260721 - A NEW COST EFFECTIVE AND SCALABLE PROCESS FOR SYNTHESIZING PURE BRIVARACETAM

 

WO2021260721 - A NEW COST EFFECTIVE AND SCALABLE PROCESS FOR SYNTHESIZING PURE BRIVARACETAM

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021260721&_cid=P12-KXX1JU-33531-1

EXAMPLES:

EXAMPLE 1: Synthesis of (3R)-N-[(1S)-1-carbamoylpropyl]-3-(hydroxymethyl) hexanamide [Intermediate 7 of scheme A of the present invention]

Example 1 illustrates one pot process for preparing purified (3R)-N-[(1S)-1- carbamoylpropyl]-3-(hydroxymethyl) hexanamide [Intermediate 7] from Intermediate 3 (80% ee) as developed in step 1 of scheme A of the present invention.

Procedure:

In the first step of scheme A of the present invention, a mixture of (R)/(S)-4-propyldihydrofuran-2(3H)-one (Intermediate 3, R: S isomer = 80: 20) (1 eq), (S)-2-aminobutanamide (1.1 eq), triethylamine (1.5 eq) is refluxed at a temperature of 95±5 °C for 24h. The mixture is then cooled to 60-65 °C, washed with a mixture of dichloromethane and diisopropyl ether (2.5 vol) in order to get Intermediate-7 [(3R)-N-[(1S)-1-carbamoyl-propyl]-3-(hydroxymethyl) hexanamide] (80% yield).

Results:

Formation of Intermediate 7 is confirmed further by following analytical studies: a) The 1H NMR analysis is conducted and the data as illustrated in accompanying figure 1 depicts: (400 MHz, DMSO-d6): δ 0.6 (t, J= Hz, 6H), 1.07-1.18 (m, 1H), 1.21-1.35 (m, 3H), 1.45-1.43 (m, 1H), 1.61-1.72 (m, 1H), 1.75-1.90 (m, 1H), 2.03 (dd, J=6.64 & 14.08 Hz, 1H), 2.18 (dd, J=7.0 & 14.08 Hz, 1H), 3.28 (t, J=5.36 Hz, 2H), 4.07-4.18 (m, 1H), 4.43 (t, J=5.2 Hz, 1H), 6.95 (s, 1H), 7.28 (s, 1H), 7.76 (d, J=8.08 Hz, 1H).; thus, confirming formation of Intermediate 7 of the present invention.

b) The LCMS analysis is further conducted and the data as graphically illustrated in accompanying figure 2 provides a (M+H+) value of 231.0; thus, confirming formation of Intermediate 7 of the present invention.

c) The HPLC study is also conducted and the data as graphically illustrated in accompanying figure 3 confirms formation of Intermediate 7 of the present invention with chiral purity of 97.38%

EXAMPLE 2: Preparation of (3R)-N-(1S)-1-amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide [Intermediate 8A of scheme A of the present invention]: Example 2 illustrates a process for preparing (3R)-N-(1S)-1-Amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide [Intermediate 8A] from Intermediate 7 of example 1 above as developed in the present invention.

Procedure:

In second step of scheme A of the present invention, the said Intermediate 7 of example 1 above that is (3R)-N-(1S)-1-Amino-1-oxobutan-2-yl)-3-(hydroxymethyl) hexanamide (~98% Chemical purity and ~97% Chiral purity) (1736.86 mmol) is dissolved in DCM (1.2 L) at RT into a RBF under N2 atm. Then the solution is cooled to 10-20 C and Oxaloyl chloride (2605.29 mmol) is added to this cooled solution at 10-20 °C. The mixture is stirred for 24 h at 25-40 °C under N2 atm. Completion of the reaction is monitored by TLC. After completion of reaction, the solvent is distilled off and the residual mass is diluted with water (6 L), stirred at 30-50 °C for 4 h. Slurry mass is then filtered and washed with water (2×400 mL) followed by MTBE (800 mL). The solid is dried under vacuum at 50-55 °C for 4-5 h to afford Intermediate 8A that is (3R)-N-(1S)-1-Amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide as a white solid (92% yield).

Results:

Formation of Intermediate 8A is confirmed further by following analytical studies: a) The 1H NMR analysis is conducted and the data as illustrated in accompanying figure 4 depicts: 1H NMR (400 MHz, DMSO-d6) : δ 0.83 (t, J=7.44 Hz, 3H), 0.85 (t, J=6.72 Hz, 3H), 1.20-1.40 (m, 4H), 1.43-1.56 (m, 1H), 2.08-2.18 (m, 1H), 2.20-2.28 (m, 2H), 3.61 (dd, J=4.6 & 10.8 Hz, 1 H), 3.67 (dd, J=4.6 & 10.8 Hz, 1H), 4.07-4.18 (m, 1H), 6.95 (s, 1H), 7.29 (s, 1H), 7.89 (d, J=8.12 Hz, 1H); thus confirming formation of Intermediate 8A of the present invention.

b) The LCMS analysis is further conducted and the data as graphically illustrated in accompanying figure 5 (a, b) provides a (M+H+) value of 249.20; thus, confirming formation of Intermediate 8A of the present invention.

EXAMPLE 3: Process for purification of Intermediate 8A forming Intermediate 8B Example 3 illustrates a process for purifying the said Intermediate 8A of example 2 above of the present invention.

Procedure:

The Intermediate 8A as obtained in example 2 above [that is (3R)-N-(1S)-1-Amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide] is first dissolved in a polar solvent like Acetonitrile raising the temperature to 50 to 60 °C; followed by stirring and then addition of another solvent methyl tert-butyl ether (MTBE) which is less polar in nature. The mixture is then cooled down to 0°C, the filtered mass thus obtained is dried in order to obtain a white solid of Intermediate 8B. The material thus obtained is further dissolved in THF (5 vol) at 60 °C, cooled to 20-30°C, followed by addition of heptane (5 vol), stirred at 10°C to 30 °C for 1 h. The mass obtained is filtered and washed with heptane (2×1 vol), dried under vacuum at 50-55°C in order to afford formation of purer form of Intermediate 8A that is Intermediate 8B that is (3R)-N-(1S)-1-amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide as a white solid having a chemical purity of 99.9% along with a chiral purity of 100% (yield: 390 g).

Results:

The purification of Intermediate 8A is further confirmed by the following analytical test results:

a) Chiral HPLC: A Chiral HPLC as illustrated in accompanying figure 6 confirmed formation of purest form of Intermediate 8B having 100% chiral purity [Peak 1; RT (min) = 6.244; %Area=100%].

b) GLP-HPLC: A GLP-HPLC as illustrated in accompanying figure 7 further confirmed formation of Intermediate 8B having 99.9% chemical purity [Peak 3; BRIV8; RT = 29.278; % Area=99.90%].

EXAMPLE 4: Synthesis of (3R)-N-[(1S)-1-carbamoylpropyl]-3-(hydroxymethyl) hexanamide [Intermediate 7’ of scheme B of the present invention]

Example 4 illustrates one pot process for preparing purified (3R)-N-[(1S)-1-carbamoylpropyl]-3-(hydroxymethyl) hexanamide [Intermediate 7’] from Intermediate 6 (99.99% ee) as developed in step-1 scheme B of the present invention.

Procedure:

In another method, in the first step of scheme B of the present invention, a mixture of (R)/(S)-4-propyldihydrofuran-2(3H)-one (Intermediate 6: S isomer = 99.99% : 0.1%) (1 eq), (S)-2-aminobutanamide (1.7 eq), triethylamine (5 eq) is refluxed at a temperature between 95±5 °C for 24 h. Then, the crude reaction mass is cooled and washed with dichloromethane and diisopropyl ether mixture (2.5 vol) in order to achieve Intermediate-7’ of scheme B of the present invention [(3R)-N-[(1S)-1-carbamoylpropyl]-3-(hydroxymethyl) hexanamide] (90% yield).

Results:

The chiral purity of the formed Intermediate 7’ is analyzed by HPLC method and the data as graphically illustrated in accompanying figure 8 confirms formation of Intermediate 7’ of the present invention with chiral purity of 99.11%

EXAMPLE 5: Preparation of (3R)-N-(1S)-1-amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide [Intermediate 8’ of scheme B of present invention]: Example 5 illustrates a process for preparing purest form of (3R)-N-(1S)-1-amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide [Intermediate 8’] from Intermediate 7’ of example 4 as developed in scheme B (step 2) of the present invention.

Procedure:

In the second step of scheme B of the present invention, the intermediate 7’ of the above example 4 that is (3R)-N-(1S)-1-amino-1-oxobutan-2-yl)-3-(hydroxymethyl) hexanamide (98% Chemical purity and >99%Chiral purity) (1736.86 mmol) is dissolved in DCM (1.2 L) at RT in a round bottomed flask under N2 atm. Then the solution is cooled to 10-30 °C and 1-Chloro-N,N,2-trimethyl-1-propenylamine (2605.29 mmol) is added to this cooled solution at 10-30 °C. The mixture is stirred for 24 h at 25-40 °C under N2 atm. Completion of the reaction is monitored by TLC. After completion of the reaction, the solvent is distilled off and the residual mass is diluted with water (6 L), stirring at 30-50 °C for 4 h. The slurry mass thus obtained is then filtered and washed with water (2×400 mL) followed by methyl tert-buty ether (MTBE) (800 mL). The solid thus obtained is dried under vacuum at 50-55 °C for 4-5 h in order to afford formation of Intermediate 8’ that is (3R)-N-(1S)-1-amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide as a white solid (92% yield).

Results:

Formation of Intermediate 8’ is confirmed further by following analytical studies: a) The 1H NMR analysis is conducted and the data as illustrated in accompanying figure 9 depicts: (400 MHz, DMSO-d6): 1H NMR (400 MHz, DMSO-d6) : δ 0.83 (t, J=7.44 Hz, 3H), 0.85 (t, J=6.72 Hz, 3H), 1.20-1.40 (m, 4H), 1.43-1.56 (m, 1H), 2.08-2.18 (m, 1H), 2.20-2.28 (m, 2H), 3.61 (dd, J=4.6 & 10.8 Hz, 1 H), 3.67 (dd, J=4.6 & 10.8 Hz, 1H), 4.07-4.18 (m, 1H), 6.95 (s, 1H), 7.29 (s, 1H), 7.89 (d, J=8.12 Hz, 1H); thus, confirming formation of Intermediate 8’ of the present invention.

b) The LCMS analysis is further conducted and the data as graphically illustrated in accompanying figure 10 provides a (M+H+) value of 249.1; thus, confirming formation of Intermediate 8’ of the present invention.

c) The HPLC data as illustrated in accompanying figure 11 confirms 100% chiral purity of Intermediate 8’.

EXAMPLE 6: Preparation of (2S)-2-[(4R)-2-oxo-4-propyl-pyrrolidin-1-yl] butanamide [Brivaracetam-API]:

Example 6 illustrates a process for preparing (2S)-2-[(4R)-2-oxo-4-propyl-pyrrolidin-1-yl] butanamide [Brivaracetam API] from Intermediate 8B of example 3 or from Intermediate 8’ of example 5 as developed in step 3 of scheme A or scheme B of the present invention respectively.

 Procedure:

In the final step of scheme A or scheme B of the present invention, the intermediate 8B of example 3 or intermediate 8’ of example 5 above that is (3R)-N-((1S)-1-Amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide (1608.04 mmol) is dissolved in dimethyl acetamide (0.5 vol) and isopropylacetate (2 L) into a RBF at 25-30 °C under N2 atm. Then 18-Crown-6 (160.79 mmol) is added into the solution and stirred at RT for 30 min. Reaction mixture is then cooled to 0-10 °C and t-BuOK (1.5 eq) is added portion wise to the cooled solution over 1 h maintaining the temperature from - 0-10 °C to 25 °C under N2 atm. Stirring is then continued for 2 h at -10 °C to 0 °C and then for 12 h at 15-25 °C under N2 atm. Completion of reaction is monitored by TLC. After completion of reaction, the reaction mixture is quenched with addition of 1M HCl solution (pH~6.5-7.0). The resulting mixture is extracted with i-PrOAc (2 L) and MTBE (1 L). Water (0.5 L) is added to the combined organic extract and then filtered through celite bed, washed the bed with MTBE-i-PrOAc (1:1) (400 mL). The organic part is separated and the aqueous part is re-extracted with i-PrOAc-MTBE (1:1) (2 ×0.8 L). The combined organic phases are washed with brine solution (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuum under a rotary evaporator to afford crude API. Distillation of dimethylacetamide solvent from the crude is then done at high vacuum pressure (0.05 mm Hg) at 70 °C. Crude product is then dissolved in isopropyl acetate (1.6 L) and treated with activated charcoal (7% w/w) to afford a tech-grade crude of Brivaracetam API as a white solid (yield: 90%) with 97.82% chemical purity.

Results:

Formation of Brivaracetam API is confirmed further by following analytical studies: a) The 1H NMR analysis is conducted and the data as illustrated in accompanying figure 12 depicts: 1H NMR (400 MHz, DMSO-d6) : δ 0.77 (t, J=7.32 Hz, 3H), 0.87 (t, J=7.2 Hz, 3H), 1.21-1.31 (m, 2H), 1.33-1.43 (m, 2H), 1.50-1.62 (m, 1H), 1.73-1.84 (m, 1H), 1.97 (dd, J=8.0 & 16.12 Hz, 1H), 2.18-2.28 (m, 1H), 2.37 (dd, J=8.4 & 16.14 Hz, 1H), 3.11 (dd, J=7.16 & 9.44 Hz, 1H), 3.36 (dd, J=9.2 & 17.5 Hz, 1H), 4.30 dd, J=5.44 & 10.28 Hz, 1H), 6.98 (s, 1H), 7.32 (s, 1H); thus, confirming formation of Brivaracetam API of the present invention.

b) The LCMS analysis is further conducted and the data as graphically illustrated in accompanying figure 13 provides a (M+H+) value of 213.0; thus, confirming formation of Brivaracetam API of the present invention.

^ Purification of Brivaracetam API:

The Brivaracetam thus formed above is further purified by means of dissolving the said material (307 g) in 30% i-PrOAc -MTBE (1 vol) at 55-60 °C, cool to 20-30°C. A mixture of Heptane and MTBE and DIPE (2:2:1) is added, stirred at 10 °C to 30°C for 1 h. The obtained mass is filtered and washed with heptane, which is subsequently dried under vacuum at 40-45 °C to afford (3R)-N-((1S)-1-amino-1-oxobutan-2-yl)-3-(chloromethyl) hexanamide as a white solid (yield: 80%, chiral purity 99.93% and chemical purity 99.94%).

Results:

a) Chiral HPLC: A Chiral HPLC as illustrated in accompanying figure 14 confirmed formation of purest form of Brivaracetam API having 99.93% chiral purity [Peak 2; RT (min) = 9.45; %Area=99.93%].

b) GLP-HPLC: A GLP-HPLC as illustrated in accompanying figure 15 further confirmed formation of Brivaracetam API having 99.9% chemical purity [Peak 2; RT = 21.138; % Area=99.94%].

NEW PATENTS, RELATED TO COVID 19

 

NEW PATENTS

1 WO/2021/258625ANTI-SAR-COV-2 (COVID-19) FULLY HUMANIZED MONOCLONAL ANTIBODY, AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

SHENZHEN INSTITUTES OF ADVANCED TECHNOLOGY CHINESE ACADEMY OF SCIENCES

2 WO/2021/260164THROMBIN C-TERMINAL PEPTIDES TO TREAT CORONAVIRAL INFECTIONS

IN2CURE AB

3 WO/2021/211332METHODS AND KITS FOR DETECTING OR DETERMINING AN AMOUNT OF AN ANTI-Β-CORONAVIRUS ANTIBODY IN A SAMPLE

ABBOTT LABORATORIES

4  WO/2021/262744KITS AND METHODS FOR ISOTHERMALLY AMPLIFYING RIBONUCLEIC ACID OF SEVERE ACUTE RESPIRATORY VIRUS COV2

UNIVERSITY OF WASHINGTON

5 WO/2021/262894METHODS FOR DIAGNOSING RESPIRATORY PATHOGENS AND PREDICTING COVID-19 RELATED OUTCOMES

THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE

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ENZYMATIC PRODUCTION OF ALLULOSE

 

WO/2021/236632

ENZYMATIC PRODUCTION OF ALLULOSE

BONUMOSE, INC.

NEW PATENT WO/2021/198525 (S,Z)-3,7-DIMETHYLNON-6-EN-1-OL AND ITS USE AS FRAGRANCE

 WO/2021/198525

(S,Z)-3,7-DIMETHYLNON-6-EN-1-OL AND ITS USE AS FRAGRANCE

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021198525&_gid=202140

GIVAUDAN SA