Diaminopyrimidine oxide: properties, uses, pros, cons, safety

Diaminopyrimidine oxide is a synthetic compound commonly used in hair care products, particularly in treatments aimed at promoting hair growth and reducing hair loss. It is known for its ability to stimulate hair follicles, improve hair density, and enhance overall scalp health. Diaminopyrimidine oxide is often found in serums, shampoos, and conditioners designed to combat thinning hair and encourage stronger, fuller hair growth.

Chemical Composition and Structure
Diaminopyrimidine oxide is a derivative of pyrimidine, a six-membered heterocyclic compound containing nitrogen atoms. The presence of two amino groups (-NH2) attached to the pyrimidine ring, along with an oxide group, gives this compound its hair growth-promoting properties. Its chemical formula is C4H6N4O, and its structure allows it to penetrate the scalp and stimulate hair follicles.

Physical Properties
Diaminopyrimidine oxide typically appears as a white to off-white crystalline powder. It is water-soluble and easily incorporated into aqueous-based formulations such as serums, lotions, and hair tonics. Due to its stability, it is often used in hair care products designed for daily use to promote hair regrowth and improve scalp health.

The name describes the structure of the molecule:

• Diaminopyrimidine refers to a pyrimidine ring structure (a six-membered aromatic ring) to which two amine groups (-NH2) are attached. Pyrimidine is a heterocyclic compound commonly found in nucleic acids such as DNA and RNA.
• Oxide indicates the presence of an oxygen (O) atom within the compound.

The synthesis process takes place in different steps:

• Synthesis of diaminopyrimidine. Diaminopyrimidine, the precursor compound of diaminopyrimidine oxide, is synthesised using appropriate starting materials and chemical reactions. The specific synthetic route may vary, but usually involves the condensation of appropriate amine and carbonyl compounds to form the diaminopyrimidine structure.
• Oxidation. The synthesised diaminopyrimidine is then subjected to an oxidation process to convert it to diamino-pyrimidine oxide. Oxidation reactions can be carried out using various oxidising agents, such as hydrogen peroxide (H2O2), nitric acid (HNO3) or other suitable oxidants. Reaction conditions, including temperature, reaction time and stoichiometry, may vary depending on the specific oxidation method used.
• Purification. After oxidation, the raw diamine oxide obtained may contain impurities. Purification techniques such as filtration, crystallisation or chromatography can be used to isolate diamine oxide and remove impurities. These purification methods help ensure a higher level of purity of the final compound.
• Characterisation and analysis. Once purified, the synthesised diamine oxide must be characterised and analysed to confirm its chemical structure and purity. Techniques such as nuclear magnetic resonance (NMR), mass spectrometry (MS) and infrared spectroscopy (IR) can be used to analyse the structure and verify the identity of the synthesised compound.

It appears as a grainy powder consisting of white crystals.

What it is used for and where

Its primary use is to care for and revitalise hair by acting on the hair follicles.  The fibrosis generated in the hair follicles hardens and tightens the collagen around the roots, creating the ideal conditions for hair loss. Diamopyrimidine Oxide has a softening effect on collagen, counteracting this phenomenon.

Cosmetics

It is a restricted ingredient III/93 as a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009.

Hair conditioning agent. A significant number of ingredients with specific and targeted purposes may co-exist in hair shampoo formulations: cleansers, conditioners, thickeners, matting agents, sequestering agents, fragrances, preservatives, special additives. However, the indispensable ingredients are the cleansers and conditioners as they are necessary and sufficient for hair cleansing and manageability. The others act as commercial and non-essential auxiliaries such as: appearance, fragrance, colouring, etc. Hair conditioning agents have the task of increasing shine, manageability and volume, and reducing static electricity, especially after treatments such as colouring, ironing, waving, drying and brushing. They are, in practice, dispersants that may contain cationic surfactants, thickeners, emollients, polymers. The typology of hair conditioning agents includes: intensive conditioners, instant conditioners, thickening conditioners, drying conditioners. They can perform their task generally accompanied by other different ingredients.

Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Typical optimal commercial product characteristics 2,4-Diamino pyrimidine-3-oxide

• Molecular Formula  C₄H₆N₄O
• Molecular Weight     126.12  g/mol
• Exact Mass   126.054161
• CAS  74638-76-9
• UNII    1756681479
• EC Number   616-121-2
• DSSTox Substance ID DTXSID40996155
• IUPAC  3-hydroxy-2-iminopyrimidin-4-amine
• InChI=1S/C4H6N4O/c5-3-1-2-7-4(6)8(3)9/h1-2,6,9H,5H2  
• InChl Key      YTKGAYFHUZTLCI-UHFFFAOYSA-N
• SMILES   C1=C(N(C(=N)N=C1)O)N
• MDL number  MFCD06410894
• PubChem Substance ID    
• ChEBI  
• ICSC    
• NSC   
• RTECS   
• UN   
• NCI

Synonyms:

• Kopexil
• 2,4-diaminopyrimidine-3-oxide
• 2,4-Diamino pyrimidine-3-oxide
• Aminexil

References__________________________________________________________________________

Garre, A., Piquero, J., Trullas, C., & Martinez, G. (2018). Efficacy and safety of a new topical hair loss-Lotion containing oleanoli c acid, apigenin, biotinyl tripeptide-1, diaminopyrimidine oxide, adenosine, biotin and ginkgo biloba in patients with androgenetic alopecia and telogen effluvium: a six-month open-label prospective clinical study. J Cosmo Trichol, 4(1000132), 2.

Abstract. In this study, minoxidil, which is well known as a pharmaceutical raw material, and diaminopyrimidine oxide (DAO), which is a cosmetic raw material, were used as active ingredients to evaluate the physical properties of niosomes and compare the skin penetrations of artificial skin. To prepare niosomes of the size of nanoparticles, a high pressure homogenization method was used, and physical properties were evaluated with a zetasizer. The particle size of the noisome including the active ingredient was measured to be 99 to 123 nm according to HLB, and the zeta potential was measured in the range of -60 to -81 mV. Through DSC (differential scanning colorimetry), it was confirmed that minoxidil, a crystalline component, was uniformly dissolved in an amorphous state in niosomes. In order to confirm and compare skin penetration, it was measured by the in vitro Franz diffusion cell method, and the niosome formulation showed 3.4 times higher penetration for minoxidil and 11.1 times higher penetration for DAO than the control gel formulation. In addition, when comparing the skin penetration of minoxidil niosome and DAO niosome, a similar trend was shown, and the penetration amount of DAO was relatively high. The shapes of the niosome formulations with different HLB values were observed using Cryo-TEM, and it was confirmed that vesicles were formed in all of them and that they were intermediate between SUV (small unilamella vesicle) and LUV (large unilamella vesicle). Through this study, minoxidil, an effective drug for hair loss, and DAO, a cosmetic raw material, can be effectively delivered to the skin by encapsulating them in a noisome formulation.

Vincenzi, C., Marisaldi, B., Tosti, A., & Patel, B. (2019). Effects of a new topical treatment containing several hair growth promoters in women with early female pattern hair loss. Skin appendage disorders, 5(3), 146-151.

Abstract. Background: Female pattern hair loss (FPHL) is increasing ly common and often presents with hair shedding. Spec tral.DNC-N® contains anti-inflammatory actives and hair growth promoters. Objectives: To assess the efficacy and tolerability of Spectral DNC-N® (DS Laboratories, Inc.) in women with early FPHL and excessive shedding. Methods: Forty-nine patients were treated with Spectral DNC-N®, applied twice daily for 3 months; 28 patients were included in the 3-month treatment extension. Efficacy assessments included the degree of hair shedding using the validated hair shedding visual scale, hair mass index (HMI), and photographic evaluation. Results: There was a statistically significant decrease in hair shedding and a corresponding increase in HMI by month 3, which was maintained through month 6. The mean investigator-assessed hair shedding score decreased from 3.5 to 2.0 and the hair mass increased from 75.8 to 84.3 mm2/cm2 by month 3 (both p < 0.01 compared with baseline). By month 6, the hair shedding score was reduced to 1.6 and the hair mass was maintained. Most patients (75%) showed an increase in global hair density. Conclusions: Spectral.DNC-N® significantly reduced hair shedding, with a corresponding increase in hair mass and density. These effects were already evident after 3 months’ treatment and further improved in those patients who continued treatment to month 6. Tolerability was good and patient satisfaction levels were high.

Loing, E., Lachance, R., Ollier, V., & Hocquaux, M. (2013). A new strategy to modulate alopecia using a combination of two specific and unique ingredients. J Cosmet Sci, 64(1), 45-58.

Synopsis. Male pattern hair loss is a major cosmetic concern affecting both genders with a preference for men. Major causes of hair loss in genetically predisposed individuals include hormonal dysfunction, loss of extracellular matrix (ECM) proteins in the follicular bed, and localized microinfl ammation. Few options are yet available to correct the problem. For this purpose, a cosmetic active ingredient was developed by combining a Trifolium pratense fl ower extract and a biomimetic peptide and tested clinically for the prevention of hair loss. Thirty volunteers with recessing hair were recruited for this randomized, placebo-controlled study. Clinical effi cacy, following daily topical application of the mixture to the scalp, was checked using TrichoScan™ for the measurement of human hair. Within 4 months of application, anagen hair increased at an average by +13%, telogen hair density decreased by −29%, and the anagen/telogen (A/T) ratio increased by +46% over baseline in the treated group. Results strongly differed from those of the placebo group (anagen, −2%; telogen, +23%; A/T ratio, −33%). Investigation of the potential mechanisms involved in the positive effects of the test product on hair growth pointed at inhibition of 5-α-reductase activity, reduction of infl ammatory reactions, and stimulation of ECM protein synthesis in the vicinity of the hair follicle.

Qiu, S., Pan, Z., Jiang, X., Lv, G., Feng, A., & Chen, H. (2024). The synergistic effect of phototherapy and active substances on hair growth. Journal of Photochemistry and Photobiology B: Biology, 259, 113008.

Abstract. Androgenic alopecia (AGA) typically manifests post-puberty, resulting in decreases in hair density, disruptions in the hair growth cycle, and alterations in hair follicle micro structure. Dihydrotestosterone (DHT) is a key hormone implicated in hair loss, especially on male. In this study, we found that each of arginine (Arg), arterial extract (AE) or biotin tripeptide-1 (BT-1), when combined with low level light therapy (LLLT, at 630 nm, 2 J/cm2), showed the efficacy in enhancing mitochondrial functions, cell proliferation and collagen synthesis in fibroblasts. Additionally, CARRIPOWER (the complexes of AE, BT-1, Arg, and Diaminopyrimidine derivatives), in conjunction with LLLT (630 nm, 2 J/cm2), showed promising results in dermal papilla cells (DPCs). The promising results contained not also inflammatory cytokines (IL-1β and IL-6) and cell pro apoptotic factor (TGF-β2) reduction, but also Wnt pathway inhibition by decreasing DKK1 level, and pro-hair growth factors (vascular endothelial growth factor (VEGF) and β-catenin) increase. This innovative combination therapy offers a potential solution for the treatment of AGA, addressing both hormonal and cellular factors involved in hair loss.