New Drug Approvals

Home » Uncategorized » Darbinurad

Darbinurad

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

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Archives

Categories

Recent Posts

Blog Stats

  • 4,798,664 hits

Unknown's avatar

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

Join 37.9K other subscribers

add to any

Share

Darbinurad

CAS 1877347-38-0

MF C18H16N2O2S MW 324.4 g/mol

[1-({[3-(4-cyanophenyl)pyridin-4-yl]sulfanyl}methyl)cyclopropyl]acetic
acid

2-[1-[[3-(4-cyanophenyl)-4-pyridinyl]sulfanylmethyl]cyclopropyl]acetic acid
urate transporter inhibitor, AYFFM7L5F0

Darbinurad is a investigational new drug that is being evaluated for the treatment of gout. It is a selective urate transporter 1 (URAT1) inhibitor that blocks the reabsorption of uric acid within the renal proximal tubule, thereby reducing serum uric acid concentrations.[1][2]

Uric acid is the final metabolite of diet and purine in human body. In vivo environment (pH 7.4, 37 degrees), uric acid is present in blood mainly in the form of sodium salt of uric acid, the serum uric acid value of normal people is generally lower than 6 mg/dL. When uric acid in serum exceeds 7 mg/dL (Shi, et al., Nature 2003, 425: 516-523), sodium salt of uric acid will crystallize out and precipitate on joints and other parts of the body, and result in disorders such as gout, urinary stones, kidney stones, etc. Patients with gout are often accompanied with other complications, including hypertension, diabetes, hyperlipidemia, dyslipidemia, atherosclerosis, obesity, metabolic disease, nephropathy, cardiovascular disease, and respiratory disease, etc. (Rock, Et al., Nature Reviews Rheumatology 2013, 9: 13-23). In 2002, Japanese scientists Endou group reported that anion transport channel protein URAT1 is a major protein responsible for reabsorption of uric acid in kidney, they also found that the blood uric acid in people with URAT1 gene mutation (causing the synthesis of such protein being interrupted, inducing nonfunctional proteins) is only one-tenth of that in normal people (Enomoto et. al., Nature 2002 417: 447-452). These findings in human genetics demonstrate that URAT1 anion transport protein in kidney plays very important role in concentration of uric acid in blood, and indicates that URAT1 is a very good and specific target of a drug for reducing blood uric acid.
      The main objective in the treatment of gout and its complications caused by higher level of blood uric acid is to reduce blood uric acid to lower than 6 mg/dL, the main methods are as follows: 1) to inhibit the generation of uric acid, such as allopurinol, febuxostat, which are drugs for inhibiting Xanthine oxidase; 2) to inhibit the reabsorption of uric acid, such as benzbromarone and probenecid, and lesinurad which is currently in clinical research, all of which are drugs for inhibiting kidney URAT1 anion transport channel protein.
      In addition to URAT1, there are other cation transport channel proteins in kidney, such as Glut9 and OAT1 etc., which are also found to be able to reabsorb uric acid back to blood from renal tubules. Kidney is a major excretion pathway of uric acid in human body (70%), intestinal system (via ABCG2 etc.,) is responsible for excreting approximate 30% of uric acid (Sakurai, et. al., Current Opinion in Nephology and Hypertension 2013, 22: 545-550).
      Human urate anion transporter 1, hURAT1, a member of anion transporter family, is located at luminal surface side of epithelial cells of renal proximal convoluted tubules, mainly participates in the reabsorption of uric acid in renal proximal convoluted tubules. URAT1 accomplishes reabsorption of uric acid and excretion of small amount of uric acid by exchanging univalent anions within cells with uric acid in lumens. Anion transport channel proteins located in renal proximal convoluted tubules also comprise anion transport channel protein OAT4, which has 42% of similarity with URAT1 (amino acids of protein). Therefore, generally, a potent URAT1 inhibitor will also inhibit OAT4 and some other anion transport channel proteins.
      At present, all the clinical drugs for reducing blood uric acid have some side effects, for example, allopurinol will cause life-threatening hypersensitivity in some populations, febuxostat has cardiovascular side effects, and benzbromarone has liver toxicity and has been taken back by Sanofi from some markets. Therefore, it is urgent to search for novel, efficient and low-toxic drugs for reducing blood uric acid, and this will have great clinical significance and application prospects.
      Thioacetate compounds have been reported in the prior art, e.g., a class of phenylthioacetate compounds were reported in CN102939279A, a class of thioacetate compounds were reported in CN103068801A, wherein thioacetate compounds in CN103068801A are obtained from the compounds in CN102939279A by essentially replacing carbons of benzene groups in skeletons of the compounds in CN102939279A with 1 to 4 N atoms.

PAT

US9856239,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US209029213&_cid=P21-MGDFSK-15618-1

Example 12: Synthesis of Compound 20

Step 1: Synthesis of 4-(4-chloropyridin-3-yl)benzonitrile (20-b)

      3-bromo-4-chloropyridine (573 mg, 3 mmol), aqueous solution of sodium carbonate (6 mL, 12 mmol, 2 M), 4-cyanophenylboronic acid (441 mg, 3 mmol) and tetrakis(triphenylphosphine)palladium (0) (173 mg, 0.15 mmol) were added to dioxane (18 mL) in a single-necked flask (50 mL), and then purged with nitrogen 3 times, the mixture was heated to 80° C. and reacted for 5 hours. The reaction solution was cooled, added with ethyl acetate (100 mL), and washed with water (100 mL) and brine (100 mL). The organic phase was dried, filtered, concentrated, and purified by preparative silica gel plate (ethyl acetate/petroleum ether: 1/4) to yield a yellow solid product.

Step 2: Synthesis of methyl 2-(1-(((3-(4-cyanophenyl)pyridin-4-yl)thio) methyl)cyclopropyl)acetate (20-c)

      Methyl 2-(1-(mercaptomethyl)cyclopropyl)acetate (840 mg, 5.25 mmol), potassium carbonate (1.45 g, 10.5 mmol) and 4-(4-chloropyridin-3-yl) benzonitrile (450 mg, 2.1 mmol) were dissolved in dimethyl formamide (20 mL) in a single-necked flask (50 mL), the mixture was heated to 130° C. and reacted for 0.5 hour. The reaction solution was cooled, added with ethyl acetate (100 ml), and washed with water (100 ml) and brine (100×3 mL). The organic phase was dried, filtered, concentrated, and purified by preparative silica gel plate (ethyl acetate/petroleum ether: 1/2) to yield a yellow oily product.

Step 3: Synthesis of 2-(1-(((3-(4-cyanophenyl)pyridin-4-yl)thio)methyl) cyclopropyl)acetic acid (20)

      Methyl 2-(1-(((3-(4-cyanophenyl)pyridin-4-yl)thio)methyl)cyclopropyl) acetate (67 mg, 0.2 mmol) and aqueous solution of sodium hydroxide (0.5 mL, 0.5 mmol, 1 M) were added to methanol (3 mL) in a single-necked flask (50 mL), and the mixture was reacted at room temperature for 5 hours. The reaction solution was adjusted to pH=3 with concentrated hydrochloric acid, concentrated and purified by preparative reverse-phase chromatography to yield a white solid product.
      LC-MS (ES, m/z): 325 [M+H] +; H-NMR (400 MHz, CDCl 3, ppm): δ 8.42 (s, 1H), 8.24 (s, 1H), 7.75 (d, J=8.4 Hz, 2H), 7.53 (d, J=8.4 Hz, 2H), 7.35-7.33 (m, 1H), 3.19 (s, 2H), 2.38 (s, 2H), 0.62-0.60 (m, 4H).

PAT

Carboxylic acid compound, method for preparation thereof, and use thereof

Publication Number: KR-102474640-B1, Priority Date: 2014-08-13, Grant Date: 2022-12-05

str1

AS ON JUNE2025 4.45 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

wdt-16

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

This image has an empty alt attribute; its file name is research.jpg

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

……

Clinical data
Other namesD-0120
Identifiers
IUPAC name
CAS Number1877347-38-0
PubChem CID118902135
ChemSpider128992995
UNIIAYFFM7L5F0
Chemical and physical data
FormulaC18H16N2O2S
Molar mass324.40 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

References

  1.  Kaufmann D, Chaiyakunapruk N, Schlesinger N (November 2024). “Optimizing gout treatment: A comprehensive review of current and emerging uricosurics”. Joint Bone Spine. 92 (2) 105826. doi:10.1016/j.jbspin.2024.105826. PMID 39622367.
  2.  “Darbinurad”. PatSnap.

/////////Darbinurad

By in Uncategorized on .

Leave a comment

This site uses Akismet to reduce spam. Learn how your comment data is processed.

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 37.9K other subscribers
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 AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 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 Open superstar 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 32 PLUS year tenure till date Feb 2023, Around 35 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 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, 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 38 lakh plus views on New Drug Approvals Blog in 227 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 He has total of 32 International and Indian awards

View Full Profile →

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.