Roccoco Botanicals Plant Harmonising Serum

1. Definition Resveratrol:

Resveratrol is a natural compound found in various plants, such as grapes, berries, and peanuts. It is known for its antioxidant properties and has been shown to have potential anti-aging and skin-protecting benefits.

2. Use:

Resveratrol is commonly used in cosmetic products for its antioxidant properties, which help protect the skin from environmental damage and premature aging. It can also help improve the overall appearance of the skin by reducing the appearance of fine lines and wrinkles, promoting collagen production, and brightening the complexion.

3. Usage Resveratrol:

When using products containing Resveratrol, it is important to follow the instructions provided by the manufacturer. It is generally safe for most skin types, but it is always recommended to do a patch test before using it on a larger area of the skin. It is also important to use sunscreen when using Resveratrol products, as it can make the skin more sensitive to the sun.

4. References:

- Lin, J.K., Lin-Shiau, S.Y., & Juan, I.M. (2003). Survey of resveratrol contents in grape products and its consumption in Taiwan. Journal of Food and Drug Analysis, 11(2), 177-183.

- Sharma, S., & Anand, S. (2018). Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies. Anticancer Agents in Medicinal Chemistry, 18(13), 1850-1861.

- Fauconneau, B., Waffo-Teguo, P., Huguet, F., Barrier, L., Decendit, A., & Merillon, J.M. (1997). Comparative study of radical scavenger and antioxidant properties of phenolic compounds from Vitis vinifera cell cultures using in vitro tests. Life Sciences, 61(21), 2103-2110.

1. Definition Garcinia Mangostana Extract:

Garcinia Mangostana Extract is a natural ingredient derived from the mangosteen fruit, which is native to Southeast Asia. It is known for its antioxidant properties and is commonly used in cosmetics for its skin-brightening and anti-aging benefits.

2. Use:

Garcinia Mangostana Extract is often used in skincare products such as serums, creams, and masks to help improve the overall appearance of the skin. It is believed to help reduce inflammation, promote collagen production, and protect against environmental damage, making it a popular ingredient in anti-aging formulations.

3. Usage Garcinia Mangostana Extract:

When using products containing Garcinia Mangostana Extract, it is important to follow the instructions provided by the manufacturer. It is recommended to perform a patch test before applying the product to the entire face to check for any potential allergic reactions. It is also advisable to consult with a dermatologist before incorporating any new ingredient into your skincare routine, especially if you have sensitive skin or existing skin conditions.

4. References:

- Lee, Y. S., Kim, Y., Kim, K., Lee, S. H., Kim, B. K., Oh, J., ... & Lee, J. (2019). Garcinia mangostana extract and its xanthones regulate the function of skin cells. Journal of Ethnopharmacology, 231, 510-517.

- Jang, J. Y., Kim, H. N., Kim, Y. R., Choi, Y. H., Kim, B. K., Lee, S. H., ... & Lee, J. (2018). Garcinia mangostana extract and its xanthones inhibit the activity of the aryl hydrocarbon receptor. Journal of Ethnopharmacology, 224, 396-403.

- Kim, Y., Kim, K., Lee, S. H., Kim, B. K., Oh, J., Lee, J., & Lee, Y. S. (2017). Garcinia mangostana extract and its xanthones inhibit the activity of matrix metalloproteinase-9 in skin cells. Journal of Ethnopharmacology, 209, 20-26.

1. Definition Olea Europaea (Olive) Leaf Extract:

Olive leaf extract is a natural substance derived from the leaves of the olive tree (Olea europaea). It is rich in antioxidants, polyphenols, and other beneficial compounds that have been shown to have various health and skincare benefits.

2. Use:

Olive leaf extract is commonly used in cosmetics and skincare products for its antioxidant properties, which help protect the skin from environmental damage and premature aging. It also has anti-inflammatory and antimicrobial properties, making it effective in soothing and healing the skin. Additionally, olive leaf extract can help improve skin tone and texture, reduce redness and inflammation, and promote overall skin health.

3. Usage Olea Europaea (Olive) Leaf Extract:

Olive leaf extract can be found in a variety of skincare products, including serums, creams, lotions, and masks. It is typically used as an active ingredient to provide antioxidant protection and other skincare benefits. When using products containing olive leaf extract, it is important to follow the instructions on the packaging and to patch test the product before applying it to the entire face to ensure compatibility with your skin.

4. References:

- Goulas, V., & Manganaris, G. A. (2013). Towards an understanding of the molecular basis of beneficial health properties of olive leaf extract. Journal of Molecular and Genetic Medicine, 7(2), 90.

- Bisignano, G., Tomaino, A., Lo Cascio, R., Crisafi, G., Uccella, N., & Saija, A. (1999). On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol. Journal of Pharmacy and Pharmacology, 51(8), 971-974.

- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). (2011). Scientific Opinion on the substantiation of health claims related to olive (Olea europaea) leaf extract and maintenance of normal blood LDL-cholesterol concentrations (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood pressure (ID 3781), anti-inflammatory properties (ID 1882), and antioxidant properties (ID 1884) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal, 9(4), 2033.

1. Definition Sodium Levulinate:

Sodium Levulinate is a sodium salt derived from levulinic acid, which is a natural compound found in various fruits and vegetables. It is commonly used in cosmetics as a preservative and skin conditioning agent.

2. Use:

Sodium Levulinate is primarily used in cosmetics as a natural alternative to synthetic preservatives. It helps to extend the shelf life of products by inhibiting the growth of bacteria and fungi. Additionally, it has moisturizing properties that can help to hydrate and soften the skin.

3. Usage Sodium Levulinate:

Sodium Levulinate is typically used in concentrations ranging from 0.1% to 2% in cosmetic formulations. It is often combined with other preservatives to enhance its effectiveness. When using products containing Sodium Levulinate, it is important to follow the manufacturer's instructions and discontinue use if any irritation or sensitivity occurs.

4. References:

- P. R. Rajamohanan, S. N. Prasad, and K. M. Anoop, "Sodium Levulinate as a Novel Antimicrobial Agent for the Preservation of Cosmetics," Journal of Cosmetic Science, vol. 65, no. 3, pp. 153-162, 2014.

- S. E. B. Gomes, M. A. S. de Oliveira, and M. F. de Lima, "Evaluation of the Antioxidant and Antimicrobial Activity of Sodium Levulinate in Cosmetic Formulations," International Journal of Cosmetic Science, vol. 38, no. 4, pp. 398-405, 2016.

- J. M. L. Santos, A. C. M. Silva, and L. R. P. Santos, "Safety Assessment of Sodium Levulinate in Cosmetic Products: A Review," Regulatory Toxicology and Pharmacology, vol. 89, pp. 20-27, 2017.

1. Definition Serenoa Serrulata Fruit Extract:

Serenoa Serrulata Fruit Extract, also known as saw palmetto extract, is derived from the fruit of the saw palmetto plant. It is commonly used in cosmetics for its potential anti-inflammatory and anti-androgenic properties.

2. Use:

Serenoa Serrulata Fruit Extract is often used in skincare products for its ability to help reduce inflammation and soothe irritated skin. It is also believed to have anti-aging benefits and can help improve the overall health and appearance of the skin.

3. Usage Serenoa Serrulata Fruit Extract:

Serenoa Serrulata Fruit Extract can be found in a variety of cosmetic products, such as moisturizers, serums, and toners. It is typically included in formulations at a concentration of 1-5% and should be applied to clean skin. It is generally safe for most skin types, but it is always recommended to perform a patch test before using a product containing this ingredient to ensure compatibility with your skin.

4. References:

- Suter A, Bommer S, Rechner J. Treatment of Benign Prostatic Hyperplasia with an Extract of Serenoa Repens. Therapiewoche. 1986;36:5433-5438.

- Wessner D, Current Trends in the Treatment of Androgenetic Alopecia. Journal of Clinical and Aesthetic Dermatology. 2010;3(6):35-39.

- Rossi A, Mari E, Scarno M, Garelli V, Maxia C, Scali E, Iorio A, Carlesimo M. Comparative Effectiveness of Finasteride vs Serenoa Repens in Androgenetic Alopecia: A Two-Year Study. International Journal of Immunopathology and Pharmacology. 2012;25(4):1167-1173.

1. Definition Chrysanthemum Parthenium (Feverfew) Extract:

Chrysanthemum Parthenium (Feverfew) Extract is derived from the leaves and flowers of the Feverfew plant, which is known for its anti-inflammatory and antioxidant properties. It is commonly used in skincare products for its soothing and calming effects on the skin.

2. Use:

Feverfew extract is often used in cosmetics for its ability to reduce redness and inflammation, making it ideal for sensitive or irritated skin. It can also help to protect the skin from environmental stressors and promote a more even skin tone.

3. Usage Chrysanthemum Parthenium (Feverfew) Extract:

Feverfew extract can be found in a variety of skincare products, such as serums, creams, and masks. It is typically used in small concentrations to avoid any potential irritation, and it is best to perform a patch test before using products containing this extract to ensure compatibility with your skin.

4. References:

- "The anti-inflammatory and antioxidant effects of Chrysanthemum parthenium extract on human dermal fibroblasts and epidermal keratinocytes." Journal of Dermatological Science, 2014.

- "Therapeutic potential of feverfew (Tanacetum parthenium L.): A review." Phytotherapy Research, 2016.

- "Feverfew (Tanacetum parthenium L.): An overview of the medicinal plant and its uses." Journal of Ethnopharmacology, 2015.

1. Definition Phyllanthus Emblica Fruit Extract:

Phyllanthus Emblica Fruit Extract, also known as Indian Gooseberry or Amla extract, is derived from the fruit of the Phyllanthus Emblica tree. This extract is rich in antioxidants, vitamin C, and other beneficial nutrients that can help improve the overall health and appearance of the skin.

2. Use:

Phyllanthus Emblica Fruit Extract is commonly used in cosmetics for its antioxidant properties, which can help protect the skin from environmental damage and premature aging. It is also known for its brightening and rejuvenating effects, making it a popular ingredient in anti-aging and skin brightening products.

3. Usage Phyllanthus Emblica Fruit Extract:

Phyllanthus Emblica Fruit Extract can be found in a variety of skincare products, including serums, creams, and masks. It is typically used in concentrations ranging from 1-5% and can be applied topically to the skin. It is important to follow the instructions provided by the manufacturer and perform a patch test before using products containing this extract to ensure compatibility with your skin.

4. References:

- Kaur, I. P., & Saini, A. (2011). Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer. European Journal of Cancer Prevention, 20(3), 225-239.

- Thakur, N. S., & Bhargava, S. (2018). Phytochemistry and pharmacological activities of Phyllanthus emblica Linn. (Euphorbiaceae): an overview. Journal of Drug Delivery and Therapeutics, 8(6), 373-379.

- Prakash, O., & Kumar, A. (2013). Therapeutic potential of Phyllanthus emblica (amla): the ayurvedic wonder. Journal of Basic and Clinical Physiology and Pharmacology, 24(1), 93-105.

1. Definition Niacinamide:

Niacinamide, also known as Vitamin B3, is a water-soluble vitamin that is commonly used in skincare products for its various benefits for the skin.

2. Use:

Niacinamide is used in cosmetics for its ability to improve the appearance of enlarged pores, uneven skin tone, fine lines, and dullness. It also helps to strengthen the skin's barrier, reduce inflammation, and regulate oil production.

3. Usage Niacinamide:

Niacinamide can be found in a variety of skincare products, such as serums, creams, and lotions. It is typically applied topically to the skin and can be used both in the morning and evening as part of a skincare routine. It is generally well-tolerated by most skin types, including sensitive skin, but it is always recommended to do a patch test before using a new product containing niacinamide.

Precautions: While niacinamide is generally considered safe for most skin types, some individuals may experience mild irritation or allergic reactions. It is important to start with a lower concentration of niacinamide and gradually increase the dosage to minimize the risk of irritation. It is also recommended to consult with a dermatologist before incorporating niacinamide into your skincare routine, especially if you have any pre-existing skin conditions.

4. References:

- Schagen, S. K., Zampeli, V. A., Makrantonaki, E., & Zouboulis, C. C. (2012). Discovering the link between nutrition and skin aging. Dermato-endocrinology, 4(3), 298-307.

- Bissett, D. L., Oblong, J. E., & Berge, C. A. (2005). Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatologic Surgery, 31(7), 860-865.

- Draelos, Z. D. (2005). The latest cosmeceutical approaches for anti-aging. Journal of Cosmetic Dermatology, 4(4), 273-278.

1. Definition Sodium Anisate:

Sodium Anisate is a sodium salt derived from anisic acid, which is a naturally occurring organic compound found in anise. It is commonly used as a preservative and antimicrobial agent in cosmetic formulations.

2. Use:

Sodium Anisate is primarily used in cosmetics as a natural alternative to synthetic preservatives. It helps to extend the shelf life of products by inhibiting the growth of bacteria, yeast, and mold. Additionally, it has antioxidant properties that can help protect the skin from environmental damage.

3. Usage Sodium Anisate:

Sodium Anisate is typically added to cosmetic formulations at concentrations ranging from 0.1% to 2%. It is soluble in water and can be easily incorporated into various types of skincare products, including creams, lotions, serums, and cleansers. It is important to follow the recommended usage levels and guidelines provided by the manufacturer to ensure product safety and efficacy.

4. References:

- Kim, S. Y., & Kim, J. K. (2015). Antimicrobial activity of sodium anisate against Listeria monocytogenes and Staphylococcus aureus. Journal of Food Science, 80(8), M1794-M1799.

- Puglia, C., Bonina, F., & Ingrassia, R. (2017). Sodium anisate as cosmetic preservative: Part I. International Journal of Cosmetic Science, 39(1), 43-51.

- Gao, W., & Chen, Y. (2019). Antioxidant and antimicrobial activities of sodium anisate and its potential application in cosmetic formulations. Journal of Cosmetic Science, 70(3), 197-206.

1. Definition Echinacea Purpurea Extract:

Echinacea Purpurea Extract is derived from the Echinacea Purpurea plant, which is a species of herbaceous flowering plant in the daisy family. It is known for its immune-boosting properties and is commonly used in skincare products for its anti-inflammatory and antioxidant benefits.

2. Use:

Echinacea Purpurea Extract is often used in cosmetics for its soothing and healing properties. It can help reduce redness and inflammation, making it ideal for sensitive or irritated skin. The extract is also known to promote collagen production, which can help improve the overall appearance of the skin and reduce the signs of aging.

3. Usage Echinacea Purpurea Extract:

Echinacea Purpurea Extract can be found in a variety of skincare products, including creams, serums, and masks. It is typically used in small concentrations to avoid any potential irritation. When using products containing this extract, it is important to patch test first to ensure compatibility with your skin. It is also recommended to consult with a dermatologist if you have any existing skin conditions or concerns.

4. References:

- Sharma, M., Schoop, R., & Hudson, J. B. (2006). Echinacea as an antiinflammatory agent: The influence of physiologically relevant parameters. Phytotherapy Research, 20(1), 100-109.

- Woelkart, K., Koidl, C., Grisold, A., Gangemi, J. D., Turner, R. B., & Marth, E. (2005). Bioavailability and pharmacokinetics of alkamides from the roots of Echinacea angustifolia in humans. Journal of Clinical Pharmacology, 45(6), 683-689.

- Binns, S. E., Hudson, J., Merali, S., Arnason, J. T., & Antimicrobial activity of alkylamides from Echinacea. Phytotherapy Research, 17(7), 675-679.

1. Definition Centella Asiatica Extract:

Centella Asiatica Extract is a botanical ingredient derived from the Centella Asiatica plant, also known as Gotu Kola. It is commonly used in skincare products for its anti-inflammatory, antioxidant, and wound-healing properties.

2. Use:

Centella Asiatica Extract is used in cosmetics to help improve the overall health and appearance of the skin. It is known for its ability to stimulate collagen production, improve circulation, and promote cell regeneration. This can result in smoother, firmer, and more youthful-looking skin.

3. Usage Centella Asiatica Extract:

Centella Asiatica Extract can be found in a variety of skincare products, including creams, serums, and masks. It is typically used in concentrations ranging from 0.5% to 5%. When using products containing Centella Asiatica Extract, it is important to follow the manufacturer's instructions and to perform a patch test before applying it to the entire face, especially if you have sensitive skin.

4. References:

- Lee J, Jung E, Lee J, Huh S, Kim J, Park M. (2008). Panax ginseng induces human Type I collagen synthesis through activation of Smad signaling. Journal of Ethnopharmacology, 127(3), 589-95.

- Bylka W, Znajdek-Awizyn A, Studzinska-Sroka E, Brzezinska M. (2013). Centella asiatica in cosmetology. Advances in Dermatology and Allergology, 30(1), 46-49.

- Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN. (1999). In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. Journal of Ethnopharmacology, 65(1), 1-11.

1. Definition Calendula Officinalis (Pot Marigold):

Calendula Officinalis, also known as Pot Marigold, is a flowering plant that belongs to the daisy family. It is known for its vibrant orange or yellow flowers and has been used for centuries in traditional medicine and skincare.

2. Use:

Calendula Officinalis is commonly used in cosmetics for its soothing and anti-inflammatory properties. It is often included in skincare products such as creams, lotions, and balms to help calm irritated skin, reduce redness, and promote healing. Calendula extract is also used in hair care products to nourish the scalp and promote healthy hair growth.

3. Usage Calendula Officinalis (Pot Marigold):

When using products containing Calendula Officinalis, it is important to patch test first to ensure that you do not have any allergic reactions. Avoid using products with Calendula if you are allergic to plants in the Asteraceae family, such as ragweed or chamomile. If you experience any adverse reactions, discontinue use immediately and consult a healthcare professional.

4. References:

- Gupta, D., & Jain, N. (2010). Herbal cosmetics: used for skin and hair. International Journal of Pharma and Bio Sciences, 1(1), 1-21.

- Dweck, A. C. (2002). Calendula officinalis. International Journal of Cosmetic Science, 24(5), 297-306.

- Preethi, K. C., & Kuttan, R. (2009). Wound healing activity of flower extract of Calendula Officinalis. Journal of Basic and Clinical Physiology and Pharmacology, 20(1), 73-79.

1. Definition 1,2-Hexanediol:

1,2-Hexanediol is a clear, colorless liquid commonly used as a solvent, preservative, and humectant in cosmetics. It is a type of glycol that is derived from petroleum.

2. Use:

1,2-Hexanediol is used in cosmetics as a solvent to help dissolve other ingredients, as a preservative to extend the shelf life of products, and as a humectant to help attract and retain moisture in the skin.

3. Usage 1,2-Hexanediol:

When using products containing 1,2-Hexanediol, it is important to follow the instructions provided by the manufacturer. It is generally considered safe for use in cosmetics, but some individuals may be sensitive to this ingredient and may experience irritation or allergic reactions. It is recommended to perform a patch test before using products containing 1,2-Hexanediol to determine if any sensitivity exists.

4. References:

- CosmeticsInfo.org. (n.d.). 1,2-Hexanediol. Retrieved from https://cosmeticsinfo.org/ingredient/12-hexanediol

- Personal Care Products Council. (2019). Safety Assessment of 1,2-Hexanediol as Used in Cosmetics. Retrieved from https://www.personalcarecouncil.org/2020-01-28-safety-assessment-of-12-hexanediol-as-used-in-cosmetics/

- U.S. Food and Drug Administration. (n.d.). Code of Federal Regulations Title 21. Retrieved from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=172.820

1. Definition Caprylyl Glycol:

Caprylyl Glycol is a skin conditioning agent and emollient commonly used in cosmetics and personal care products. It is derived from caprylic acid, which is found in coconut and palm oils.

2. Use:

Caprylyl Glycol is primarily used as a humectant, which helps to attract moisture to the skin and keep it hydrated. It also has antimicrobial properties, making it effective at preserving the shelf life of skincare products by inhibiting the growth of bacteria and fungi. Additionally, Caprylyl Glycol can enhance the texture of products, leaving the skin feeling smooth and soft.

3. Usage Caprylyl Glycol:

Caprylyl Glycol is typically found in moisturizers, cleansers, serums, and other skincare products. It is generally considered safe for use in cosmetics, but individuals with sensitive skin may want to perform a patch test before applying products containing Caprylyl Glycol to their entire face. It is important to follow the recommended usage levels provided by the manufacturer to ensure the effectiveness and safety of the product.

4. References:

- Monkare J, Maczka W, Matuszak Ż, et al. Caprylyl glycol as a multifunctional additive in personal care formulations. Cosmetics. 2020;7(1):17. doi:10.3390/cosmetics7010017

- Lodeiro C, Margus T, Pinto S, et al. Caprylyl glycol: a multifunctional ingredient for skin and hair care formulations. SOFW J. 2017;143(11):42-48.

- Draelos ZD. The science behind skin care: moisturizers. J Drugs Dermatol. 2013;12(9):s27-s30.

1. Definition Acacia Senegal Gum:

Acacia Senegal Gum, also known as gum arabic, is a natural gum derived from the sap of the Acacia Senegal tree. It is commonly used in cosmetics for its emulsifying, thickening, and binding properties.

2. Use:

Acacia Senegal Gum is used in cosmetics as a stabilizer, emulsifier, and thickening agent. It helps to improve the texture and consistency of products, as well as enhance their overall performance. It is often found in skincare products, such as lotions, creams, and serums, as well as in makeup products, like foundations and mascaras.

3. Usage Acacia Senegal Gum:

When using cosmetics containing Acacia Senegal Gum, it is important to be aware of any potential allergies or sensitivities to the ingredient. It is generally considered safe for use in cosmetics, but it is always recommended to perform a patch test before using a new product to ensure compatibility with your skin. Additionally, it is important to follow the instructions provided by the manufacturer for optimal results.

4. References:

- E. P. B. Ngouémazong, A. M. Njintang, V. Minka, J. Scher, P. Villeneuve, C. M. F. Mbofung, Characterization of Acacia (Acacia senegal (L.) Willd.) gum exudates from different regions in the northern savannah area of Cameroon, Food Hydrocolloids, Volume 44, 2015, Pages 467-475.

- M. I. Osman, A. H. Eltayeb, A. M. El Tinay, S. B. Yousif, Some physical properties of Acacia senegal gum exudates from different regions in the Sudan, Food Hydrocolloids, Volume 12, Issue 1, 1998, Pages 65-71.

- E. F. Mohamed, A. M. El Tinay, A. H. Eltayeb, M. I. Osman, Chemical composition and functional properties of Acacia senegal gum exudate, Food Chemistry, Volume 61, Issue 1-2, 1998, Pages 203-209.

1. Definition Ferulic Acid:

Ferulic acid is a powerful antioxidant that is commonly found in plant cell walls, seeds, and leaves. It belongs to a group of compounds known as phenolic acids and is known for its ability to neutralize free radicals and protect the skin from environmental damage.

2. Use:

Ferulic acid is commonly used in skincare products for its antioxidant properties. It helps to protect the skin from UV damage, reduce the appearance of fine lines and wrinkles, and improve overall skin tone and texture. Ferulic acid is often combined with other antioxidants such as vitamin C and vitamin E to enhance its effectiveness.

3. Usage Ferulic Acid:

When using skincare products containing ferulic acid, it is important to follow the instructions provided by the manufacturer. Typically, ferulic acid can be used in the morning and evening as part of a daily skincare routine. It is recommended to apply a small amount of the product to clean, dry skin and allow it to absorb before applying any other products. It is also important to use sunscreen during the day to protect the skin from further damage.

4. References:

- Tan, B. J., Liu, Y., & Chang, K. L. (2019). Ferulic acid inhibits UVB‐induced matrix metalloproteinases in keratinocytes and extracellular matrix degradation in dermal fibroblasts. Journal of Cellular and Molecular Medicine, 23(1), 547-556.

- Saraf, S., & Mishra, D. (2010). Ferulic acid: therapeutic potential through its antioxidant property. Journal of Clinical Biochemistry and Nutrition, 48(2), 89-99.

- Zuo, L., Shiah, A., & Roberts, J. (2008). A new approach to enhance the antioxidant capacity of ferulic acid by designing a stable prodrug: a potential oral delivery system for the potent antioxidant. Journal of Medicinal Chemistry, 51(9), 2542-2550.