Fosrugocrixan

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Fosrugocrixan

CAS 2408145-38-8

MF C19H26N5O4PS2, MW483.5 g/mol

[(2R)-2-[[2-amino-5-[(1S)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentyl] dihydrogen phosphate

(2R)-2-[(2-amino-5-{[(1S)-1-phenylethyl]sulfanyl}[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentyl dihydrogen phosphate
CX3C chemokine receptor 1 (CX3CR1) antagonist, antiinflammatory, 4ZXD25SC4S, KAND-145, KAND 145

OriginatorKancera
DeveloperNovakand Pharma
ClassAnti-inflammatories; Antineoplastics; Small molecules
Mechanism of ActionChemokine CXCL13 inhibitors
Phase IOvarian cancer
PreclinicalChronic lymphocytic leukaemia
No development reportedInflammation
22 Sep 2025Kancera is now called Novakand Pharma
28 Apr 2025No recent reports of development identified for preclinical development in Ovarian-cancer in Sweden (IV)
03 May 2024Efficacy and adverse event data from a phase I trials in healthy volunteers released by Kancera

Fosrugocrixan (also known by its developmental code KAND145) is a novel, small-molecule drug candidate acting as a selective antagonist for CX3C chemokine receptor 1 (CX3CR1), commonly known as the fractalkine receptor.

Key Characteristics and Mechanism

Drug Class: It represents a first-in-class small molecule immune modulator.
Phosphate Prodrug: Fosrugocrixan is designed as a soluble phosphate prodrug. Once inside the body (in vivo), it converts into its active drug form, rugocrixan (formerly KAND567).
Mechanism of Action: By blocking the CX3CR1 fractalkine pathway, it controls and prevents the trafficking of disease-promoting immune cells. This blockage provides potent anti-inflammatory activity.

Clinical Development and Targets

The drug is being actively developed by Novakand Pharma (a company formerly known as Kancera). Its primary therapeutic targets span several conditions driven by runaway inflammation and immune responses:

Cardiovascular Diseases: Specifically targeted to manage conditions where hyper-inflammation damages tissue (such as post-myocardial infarction or heart conditions).
Autoimmune & Inflammatory Diseases: Evaluated for broad anti-inflammatory potential.
Oncology: Investigated for its ability to regulate the tumor microenvironment.

SYN

WO 2020008064

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020008064&_cid=P21-MPQB4Y-95682-1

SYN

Karlström et al. J. Med. Chem., 2013, 56, 3177-3190

https://pubs.acs.org/doi/10.1021/jm3012273

PAT

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=25F7EEC83623D484A1CFC460F518D56A.wapp2nB?docId=US458057934&_cid=P21-MPQAOO-82527-1

(2R)-2-[(2-Amino-5-{[(1S)-1-phenylethyl]sulfanyl}[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentyl dihydrogen phosphate (B), are known to act as antagonists of the fractalkine receptor (CX3CR1) (Karlström et al. J. Med. Chem., 2013, 56, 3177-3190; WO 2020/008064)

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US336567291&_cid=P21-MPQAYT-90868-1

Example 1

Preparation of (2R)-2-[(2-Amino-5-{[(1S)-1-phenylethyl]sulfanyl}[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentyl dihydrogen phosphate

Phosphorus oxychloride (337 mg, 2.2 mmol) was dissolved in THE (0.75 mL) and water (25 mg, 1.4 mmol) was added. The mixture was cooled in an ice-bath and pyridine (111 mg, 113 μL, 1.4 mmol) was added followed by (2R)-2-[(2-amino-5-{[(1S)-1-phenylethyl]sulfanyl}-[1,3] thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol hydrochloride (110 mg, 0.25 mmol) (Karlstr6m S., et al., J. Med. Chem., 2013, 56, 3177-3190; WO 2006/107258). The reaction mixture was stirred at ice-bath temperature for 1 h. To a mixture of phosphorus oxychloride (337 mg, 2.2 mmol) and water (25 mg, 1.4 mmol) in THE was added, at ice-bath temperature pyridine (111 mg, 113 μL, 1.4 mmol). Half of this mixture was added to the reaction mixture described above. The reaction mixture was stirred at ice-bath temperature for another 1 h. Water (3 mL) was added and the reaction mixture was stirred for 15 min at ice-bath temperature and 20 min at room temperature. DCM (3 mL) was added and the phases were separated. The aqueous phase was extracted with another portion of DCM (3 mL) and the organic phases were combined. At this point the product started to precipitate as a pale-yellow gum in the organic phase. MeOH was added and the now homogeneous solution was transferred to a round-bottomed flask and was evaporated to yield 120 mg of crude product, which according to HPLC was ca. 93% pure. The crude material was dissolved in a MeOH/water mixture and the pH was adjusted to about 6-7 with 1 M NaOH. The material was purified by preparative HPLC (basic method). The pure fractions were pooled, evaporated, and dried in vacuum. The product was assumed to be the diammonium salt after purification. ¹H NMR (600 MHz, CD ₃OD) δ _Hppm 7.43-7.47 (m, 2H) 7.30-7.35 (m, 2H) 7.20-7.24 (m, 1H) 5.08 (q, J=7.03 Hz, 1H) 4.59-4.68 (m, 1H) 3.92 (ddd, J=10.12, 5.67, 4.30 Hz, 1H) 3.88 (dt, J=10.12, 4.94 Hz, 1H) 1.74 (d, J=7.03 Hz, 3H) 1.71-1.79 (m, 1H) 1.68 (ddd, J=13.87, 9.54, 5.67 Hz, 1H) 1.57 (ddd, J=13.87, 8.54, 5.33 Hz, 1H) 0.98 (d, J=6.71 Hz, 3H) 0.96 (d, J=6.56 Hz, 3H). MS (ESI ⁺) m/z 484 [M+H] ⁺.

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