What are Deuterated Compounds?
Deuterated compounds refer to new compounds obtained by replacing one or more C-H bonds in a molecule with D atoms.
Deuterated reagents are an important class of high-value-added chemicals. In addition to being widely used as solvents (such as CD3OD, d-DMSO, and CDCl3) in the field of nuclear magnetic resonance (NMR), they have also become a hot topic in new drug research and development in recent years. Replacing hydrogen atoms with deuterium atoms alters the structure and properties of the compound, thereby optimizing the pharmacokinetics of drug molecules and reducing toxicity.
Advantages of Deuterated Compounds
Due to the higher stability of carbon-deuterium bonds compared to carbon-hydrogen bonds, deuteration can be used in drug development to improve pharmacokinetic characteristics. Based on their unique properties, deuterium modifications are considered one of the methods to enhance drug properties. By substituting active sites of drug molecules with deuterium, the following benefits can be achieved:
Improved pharmacokinetic properties: Deuteration can slow down the metabolism rate of drugs, increase drug exposure and half-life in the body, potentially reducing dosing frequency and dosage.
Enhanced drug selectivity: Deuteration helps reduce the formation of non-selective metabolites, thereby improving the target selectivity of drugs.
Reduced toxicity: By altering drug metabolism pathways, deuteration can decrease the formation of toxic metabolites, improving drug safety.
Increased oral bioavailability: In some cases, deuteration can enhance the oral absorption of drugs, enabling more efficient absorption into the bloodstream from the gastrointestinal tract.
Stabilization of chemically unstable stereoisomers: Deuteration can stabilize chiral centers prone to racemization or epimerization, thereby enhancing drug efficacy and reducing side effects.
Exploration of new mechanisms: In certain situations, deuteration may affect the interaction between the drug and its target, offering new mechanisms for drug discovery.
Moreover, deuterated compounds have demonstrated promising applications in biological metabolism analysis, NMR, optoelectronic materials, scientific research detection, intermediate labeling, drug development, pollution source tracing, and other fields.
Global pharmaceutical research institutions are making every effort to employ deuteration strategies to develop superior drug molecules to address unmet clinical needs. Fortunately, several deuterated drugs have been approved for market release so far, and their safety has been well-validated. Below, we summarize and analyze the deuterated drugs that have been approved and their preparation strategies for reference and inspiration for professionals.
Deutetrabenazine (Austedo)
In April 2017, the FDA approved Deutetrabenazine (Austedo) for the treatment of Huntington’s disease, making it the first deuterated drug developed and approved for market release.
Tetrabenazine and its primary metabolites, α-dihydrotetrabenazine (α-HTBZ) and β-dihydrotetrabenazine (β-HTBZ), are selective and potent inhibitors of VMAT2 (vesicular monoamine transporter 2).
The purpose of d6-tetrabenazine is to improve the pharmacokinetic properties of the active metabolites α-HTBZ and β-HTBZ. The trideuteromethyl group (CD3) in d6-tetrabenazine exhibits slower CYP-mediated carbon-deuterium bond cleavage compared to the carbon-hydrogen bond cleavage in the methyl group (CH3) of tetrabenazine. In vitro studies have demonstrated that this selective attenuation effect reduces the O-demethylation of α-HTBZ and β-HTBZ.
The increased stability of deuterated α-HTBZ and β-HTBZ, as well as the corresponding reduction in O-demethylated metabolites, has been confirmed through in vitro metabolism assays.
Tetrabenazine chemicals at BOC Sciences
| Catalog | Product Name | CAS Number | Category |
| B2693-451175 | Tetrabenazine | 58-46-8 | Impurities |
| Tetrabenazine-[d7] | Stable Isotope Labelled Compounds | ||
| rac-(2,3)-Dihydro Tetrabenazine [Cis/Trans Mixture] | Impurities | ||
| Tetrabenazine N-Oxide | Impurities | ||
| Tetrabenazine Related Impurity 18 (2R,3S,11bS, D-Val) | Impurities | ||
| Tetrabenazine Related Impurity 29 | Impurities | ||
| Tetrabenazine Related Impurity 4 | Impurities | ||
| 10111-00-9 | 2-Hydroxy Tetrabenazine | 10111-00-9 | Impurities |
| 1026016-83-0 | (3R,11bR)-Tetrabenazine | 1026016-83-0 | Impurities |
| 1026016-84-1 | (-)-Tetrabenazine | 1026016-84-1 | Impurities |
| 1065193-41-0 | ent-9-Desmethyl-alpha-Dihydro-Tetrabenazine | 1065193-41-0 | Impurities |
| 1214267-68-1 | 9-Desmethyl-beta-Dihydro Tetrabenazine | 1214267-68-1 | Impurities |
| 1217719-21-5 | beta-Hydroxy Tetrabenazine-[d7] | 1217719-21-5 | Stable Isotope Labelled Compounds |
| 1217744-19-8 | alpha-Hydroxy Tetrabenazine-[d7] | 1217744-19-8 | Stable Isotope Labelled Compounds |
| 1223399-57-2 | (3R,11bR)-Tetrabenazine (1S)-(+)-10-Camphorsulfonate | 1223399-57-2 | Impurities |
| 1381929-92-5 | Tetrabenazine Related Impurity 2 | 1381929-92-5 | Impurities |
| 149183-89-1 | 9-Desmethyl Tetrabenazine | 149183-89-1 | Impurities |
| 171598-74-6 | alpha-Hydroxy Tetrabenazine | 171598-74-6 | Impurities |
| 19328-35-9 | Tetrabenazine Related Impurity 3 | 19328-35-9 | Impurities |
| 3466-75-9 | Hydroxy Tetrabenazine | 3466-75-9 | Impurities |
| 99672-64-7 | Tetrabenazine Related Impurity 1 | 99672-64-7 | Impurities |
| B1929-482407 | Tetrabenazine-[d6] | 1392826-25-3 | Stable Isotope Labelled Compounds |
| B2694-342652 | 9-Desmethyl-alpha-Dihydro-Tetrabenazine | 1065193-59-0 | Impurities |
| cis-Dihydrotetrabenazine Glucuronide | Impurities | ||
| trans-Dihydrotetrabenazine Glucuronide | Impurities | ||
| 164104-49-8 | (2S,3S,11bS)-Dihydrotetrabenazine | 164104-49-8 | Impurities |
| 20232-39-7 | 3,4-Dihydro-6,7-dimethoxyisoquinoline Hydrochloride | 20232-39-7 | Impurities |
| 2714430-89-2 | cis-Dihydrotetrabenazine Glucuronide-[d6] | 2714430-89-2 | Stable Isotope Labelled Compounds |
| 2983160-14-9 | trans-Dihydrotetrabenazine Glucuronide-[d6] | 2983160-14-9 | Stable Isotope Labelled Compounds |
| 5220-98-4 | (±)-9-deMe-DTBZ | 5220-98-4 | Impurities |
| 862377-27-3 | (2S,3S,11bR)-Dihydrotetrabenazine | 862377-27-3 | Impurities |
| 862377-29-5 | (2R,3R,11bS)-Dihydrotetrabenazine | 862377-29-5 | Impurities |
| 862377-31-9 | (2R,3S,11bR)-Dihydrotetrabenazine | 862377-31-9 | Impurities |
| 862377-33-1 | (2S,3R,11bS)-Dihydrotetrabenazine | 862377-33-1 | Impurities |
| 924854-62-6 | (2R,3S,11bS)-Dihydrotetrabenazine | 924854-62-6 | Impurities |
| B0084-474971 | Valbenazine | 1025504-45-3 | Impurities |
| B1370-039615 | 1,11b-Dedihydrotetrabenazine | 100322-43-8 | Impurities |
| B2693-342948 | (+)-beta-Dihydrotetrabenazine | 924854-60-4 | Impurities |
| B2694-099293 | (+)-alfa-Dihydrotetrabenazine | 85081-18-1 | Impurities |
Donafenib (Sorafenib-d3)
Donafenib is a novel oral small-molecule, multi-targeted, multi-kinase inhibitor anti-tumor drug. It achieves dual effects of inhibiting tumor cell proliferation and tumor angiogenesis by suppressing the activity of multiple receptor tyrosine kinases, including VEGFR and RAF.
On June 9, 2021, Donafenib tablets were approved for marketing by the National Medical Products Administration (NMPA) through priority review.
Donafenib is used to treat various cancers. It is a deuterated multi-kinase inhibitor formed by replacing the key metabolic site of sorafenib (pyridylmethylamide) with pyridyl trideuteromethylamide.
In head-to-head clinical trials with sorafenib, Donafenib demonstrated superior metabolic characteristics, efficacy, and safety compared to sorafenib.
Sorafenib chemicals at BOC Sciences
| Catalog | Product Name | CAS Number | Category |
| B0084-065081 | Sorafenib | 284461-73-0 | Impurities |
| Sorafenib related compound 5 | Impurities | ||
| Sorafenib Impurity C | Impurities | ||
| Sorafenib Impurity 1 | Impurities | ||
| Sorafenib Impurity 10 | Impurities | ||
| Sorafenib Impurity 4 | Impurities | ||
| Sorafenib Impurity 5 | Impurities | ||
| Sorafenib Impurity 8 | Impurities | ||
| Sorafenib Related Compound 21 | Impurities | ||
| Sorafenib Related Compound 24 | Impurities | ||
| Sorafenib Related Compound 26 HCl | Impurities | ||
| 1129683-88-0 | Sorafenib related compound 8 | 1129683-88-0 | Impurities |
| 1130164-93-0 | Sorafenib-beta-D-Glucuronide | 1130164-93-0 | Impurities |
| 1207560-07-3 | Sorafenib-[d4] | 1207560-07-3 | Stable Isotope Labelled Compounds |
| 1256817-30-7 | Sorafenib Related Compound 16 | 1256817-30-7 | Impurities |
| 1261456-08-9 | Sorafenib Related Compound 25 | 1261456-08-9 | Impurities |
| 1285533-84-7 | Sorafenib related compound 3 | 1285533-84-7 | Impurities |
| 1431697-81-2 | Sorafenib 2-Chloro Isomer | 1431697-81-2 | Impurities |
| 2004659-83-8 | Sorafenib related compound 11 | 2004659-83-8 | Impurities |
| 2004659-84-9 | Sorafenib Related Compound 12 | 2004659-84-9 | Impurities |
| 2004659-85-0 | Sorafenib Related Compound | 2004659-85-0 | Impurities |
| 2056030-06-7 | Sorafenib Hemitosylate | 2056030-06-7 | Impurities |
| 220000-87-3 | Sorafenib Impurity 2 | 220000-87-3 | Impurities |
| 2204442-52-2 | Des-(4-chloro-3-trifluoromethyl)-4-(methyl-4-hydroxypicolinate) Sorafenib | 2204442-52-2 | Impurities |
| 2206827-14-5 | Sorafenib EP Impurity D | 2206827-14-5 | Impurities |
| 284461-74-1 | Sorafenib Related Compound 14 | 284461-74-1 | Impurities |
| 284462-89-1 | Sorafenib Related Compound 22 | 284462-89-1 | Impurities |
| 3505-87-1 | Sorafenib Impurity 7 | 3505-87-1 | Impurities |
| 370-50-3 | Sorafenib Impurity I | 370-50-3 | Impurities |
| 573673-43-5 | Sorafenib Carboxylic Acid Methyl Ester | 573673-43-5 | Impurities |
| 583840-03-3 | Sorafenib-N-oxide | 583840-03-3 | Impurities |
| 583840-04-4 | N-Desmethyl Sorafenib (Pyridine)-N-oxide | 583840-04-4 | Impurities |
| 845306-04-9 | Sorafenib Related Compound 13 | 845306-04-9 | Impurities |
| 862875-16-9 | Sorafenib Impurity 9 | 862875-16-9 | Impurities |
| 88330-63-6 | Sorafenib Related Compound 17 | 88330-63-6 | Impurities |
| B0046-464111 | Sorafenib tosylate | 475207-59-1 | Impurities |
| B1630-479761 | Sorafenib related compound 10 | 1012058-78-4 | Impurities |
| B2694-233982 | Sorafenib related compound 2 | 18585-06-3 | Impurities |
| B2694-479766 | Sorafenib Related Compound 15 | 284670-98-0 | Impurities |
| B2702-263928 | Sorafenib-[d3] | 1130115-44-4 | Stable Isotope Labelled Compounds |
Mintegravir (VV116, Deuterium Remdesivir Hydrobromide Tablets)
VV116 is a novel oral nucleoside antiviral drug that acts by non-covalently binding, in its triphosphate form, to the active center of SARS-CoV-2 RNA polymerase. This directly inhibits the activity of viral RNA polymerase, thereby blocking the replication of progeny viruses and achieving an antiviral effect.
The development strategy for VV116 was based on modifying the structure of GS-441524 to enhance oral bioavailability (through ester substitution and deuteration) and improve safety. The mechanism of action for VV116 in the body is consistent with that of remdesivir, but VV116 offers the advantage of high oral bioavailability, enabling oral administration.
On January 29, 2023, VV116 was conditionally approved for the treatment of COVID-19 by the National Medical Products Administration (NMPA). It was also approved for marketing in Uzbekistan in the same year.
Remdesivir chemicals at BOC Sciences
| Catalog | Product Name | CAS Number | Category |
| B2692-291708 | Remdesivir | 1809249-37-3 | Impurities |
| Remdesivir metabolite GS-441524 O-beta-D-glucuronide | Impurities | ||
| 1911578-74-9 | Remdesivir nucleoside monophosphate | 1911578-74-9 | Impurities |
| 1911578-76-1 | Remdesivir monophosphate | 1911578-76-1 | Impurities |
| 1355050-21-3 | GS-443902 trisodium | 1355050-21-3 | Impurities |
| 1355149-45-9 | GS-443902 | 1355149-45-9 | Impurities |
| B2693-012542 | GS-441524 | 1191237-69-0 | Impurities |
Deucracitinib (BMS-986165)
In September 2022, the FDA approved Bristol-Myers Squibb’s deucracitinib (BMS-986165), a potent and selective tyrosine kinase 2 (Tyk2) inhibitor, for the treatment of psoriasis.
Deucracitinib represents a novel approach in psoriasis treatment by specifically targeting the Tyk2 pathway, which plays a key role in modulating immune responses. This approval marked a significant advancement in the management of immune-mediated diseases, offering patients a new, effective therapeutic option.
Deuruxolitinib (D8-Ruxolitinib)
Deuruxolitinib is an oral selective inhibitor of JAK1 and JAK2. It received Fast Track designation from the U.S. FDA in January 2018.
In July 2020, the FDA granted Breakthrough Therapy Designation to deuruxolitinib for the treatment of adults with moderate-to-severe alopecia areata.
In October 2023, the FDA accepted Sun Pharmaceutical’s New Drug Application (NDA) for deuruxolitinib, a potential “best-in-class” oral JAK inhibitor, for the treatment of moderate-to-severe alopecia areata. This highlights its promise as a novel therapeutic option for patients suffering from this autoimmune condition.
Remdesivir chemicals at BOC Sciences
| Catalog | Product Name | CAS Number | Category |
| B0084-156872 | Ruxolitinib | 941678-49-5 | Inhibitor |
| 1092939-16-6 | Ruxolitinib sulfate | 1092939-16-6 | Inhibitor |
| 1513883-31-2 | Ruxolitinib-[d4] | 1513883-31-2 | Stable Isotope Labelled Compounds |
| 941685-37-6 | (S)-Ruxolitinib | 941685-37-6 | Inhibitor |
| B0084-321795 | Ruxolitinib phosphate | 1092939-17-7 | Inhibitor |