Photostable Mimic of Macular Pigment

Abstract

The present invention describes a visible light absorbing compound. The compound has a visible light absorption maximum between 430 nm and 480 nm and a maximum full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the visible light absorption maximum, wherein the compound is photostable. The compound is also thermostable. The compound substantially mimics the visible light absorption characteristics of macular pigment while maintaining photostability and thermostability. The compound can be used in a variety of articles, including ophthalmic devices. Formula (I):

Description

[0001] Related Applications

[0002] This application claims priority to U.S. Patent Application Serial No. 17 / 456,659, filed on November 29, 2021, which claims priority to U.S. Provisional Patent Application Serial No. 63 / 127,382, filed on December 18, 2020, the entire disclosures of which are incorporated herein by reference. Technical Field

[0003] The present invention relates to visible light absorbers. More specifically, the present invention relates to compounds that substantially mimic the visible light absorption properties of macular pigment while maintaining photostability. The compounds can be used in a variety of articles, including ophthalmic devices. Background Art

[0004] Human eye tissues contain the dietary carotenoids lutein (L) and zeaxanthin (Z), collectively referred to as macular pigment (MP). Several reports have described the benefits of MP, such as acting as a short wavelength (blue light) filter and a potent antioxidant. MP is also believed to provide protection against age-related macular degeneration (AMD) (Bernstein, P.S., Li, B., Vachali, P.P., Gorusupudi, A., Shyam, R., Henriksen, B.S., Nolan, J.M., Prog. Retin. Eye Res., 2016, 50, pp. 34-66; Beatty, S., Boulton, M., Koh, H-H., Murray, I, J., Br. J. Ophthalmol, 1999, 83, pp. 867-877). Further findings have shown that macular pigment is significantly associated with light stress recovery time, reduced disability glare contrast threshold, and reduced visual discomfort (Stringham, J.M., Garcia., P.V., Smith, P.A., McLin, L, N., Foutch, B.K., IOVS, 2011, 52(10), pp. 7406-7415).

[0005] The chemical entities associated with macular pigment are carotenoid derivatives, which have extensive unsaturation and are highly reactive towards alkene isomerization and oxidation upon photoexcitation. The antioxidant protection mechanism provided by carotenoids is essentially sacrificial, where excitation of the pi-system leads to reaction of its excited state with triplet oxygen, thereby protecting / limiting the excitation and reaction of other photosensitive compounds in the ocular environment. See, for example, Ribeiro et al., Food and Chemical Toxicology, Vol. 120, pp. 681-699 (2018); Burton et al., Burton et al., Canadian Journal of Chemistry (Can. J. Chem.), Vol. 92, pp. 305-316 (2014); Ty et al., Journal of Oil Palm Research, Vol. II No. 1, pp. 62-78 (June 1999); Johnston et al., Plos One, Vol. 9 No. 10, pp. 1-10 (2014); and Boon et al., Critical Reviews in Food Science and Nutrition, Vol. 50, pp. 515-532 (2010).

[0006] While it is desirable to incorporate macular pigment into products for the purpose of providing ocular protection, the lack of overall stability (thermal, oxidative, and photochemical stability) of carotenoids presents a very high barrier to the development of such products. Thus, it would be a significant breakthrough if new stable materials that mimic the light absorption properties of macular pigment were developed. Summary of the Invention

[0007] The present invention relates to compounds that absorb light in the wavelength range of 400 nm to 500 nm and have an absorption spectrum that substantially mimics the absorption spectrum of macular pigment. Such compounds are also photostable, e.g., when measuring changes / loss of absorption properties upon exposure to conditions similar to those described in ICH Q1B. In addition, the compounds can exhibit high extinction coefficients at desired wavelengths in the range of 400 nm to 500 nm and can thus be used at low concentrations to provide their light absorption beneficial effects. Further, these compounds are thermally stable. The compounds described herein can be used, for example, in ophthalmic devices to, for example, supplement the macular pigment optical density (MPOD) of a wearer.

[0008] Thus, in one aspect, the present invention provides a compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) at the maximum visible light absorption of at least 35 nm and at most 150 nm, preferably at most 100 nm, wherein the compound is photo-stable. The compound may exhibit a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 .

[0009] In another aspect, the present invention provides a compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) at the maximum visible light absorption of at least 35 nm and at most 150 nm, preferably at most 100 nm, wherein the compound is more photo-stable than macular pigment. The compound may exhibit a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 .

[0010] In another aspect, the present invention provides a compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) at the maximum visible light absorption of at least 35 nm and at most 150 nm, preferably at most 100 nm, wherein the compound is thermally stable. The compound may exhibit a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 .

[0011] In another aspect, the present invention provides a compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) at the maximum visible light absorption of at least 35 nm and at most 150 nm, preferably at most 100 nm, wherein the compound is more thermally stable than macular pigment. The compound may exhibit a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 .

[0012] In another aspect, the present invention provides a compound comprising a chromophore having a sub-structure of Formula I:

[0013]

[0014] wherein EWG is an electron-withdrawing group. The compound may exhibit a maximum visible light absorption in the range of 440 nm to 480 nm, or 450 nm to 475 nm or 460 nm to 470 nm.

[0015] In yet another aspect, the present invention provides an ophthalmic device comprising a compound as described herein.

[0016] In yet another aspect, the present invention provides a method for preparing a compound as described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The UV-VIS absorption spectra of 0.1 mM methanol solutions of Compound A and Compound B of the present invention superimposed on the literature spectrum of macular pigment are shown.

[0018] Figure 2 The UV-VIS transmission spectrum of a contact lens prepared from Compound B is shown.

[0019] Figure 3 The UV-VIS transmission spectra of a contact lens prepared from Compound B before and after thermo- or photo-stress treatment are shown. DETAILED DESCRIPTION

[0020] It should be understood that the present invention is not limited to the details of the construction or process steps set forth in the following description. With the teachings herein, the present invention is capable of other embodiments and of being practiced or carried out in various ways.

[0021] The following definitions are provided with respect to the terms used in the present disclosure.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Polymer definitions conform to those disclosed in Compendium of Polymer Terminology and Nomenclature, IUPAC Recommendations 2008, edited by Richard G. Jones, Jaroslav Kahovec, Robert Stepto, Edward S. Wilks, Michael Hess, Tatsuki Kitayama and W. Val Metanomski, IUPAC Recommendations 2008. All publications, patent applications, patents and other references mentioned herein are incorporated herein by reference.

[0023] As used herein, the term “(meth)yl” means an optional methyl substitution. Thus, terms such as “(meth)acrylate” denote both methacrylate and acrylate.

[0024] Wherever chemical structures are provided, it should be understood that the alternative options disclosed for substituents on the structure can be combined in any combination. Thus, if a structure contains substituents R* and R**, each of which contains three lists of possible groups, nine combinations are disclosed. The same applies to combinations of features.

[0025] When subscripts (such as "n" in the general formula n are used to describe the number of repeating units in the chemical formula of a polymer, the formula should be interpreted as representing the number-average molecular weight of the macromolecule.

[0026] The term "individual" includes humans and vertebrates.

[0027] The term "biomedical device" refers to any article designed to be used in or on mammalian tissue or body fluids and preferably in or on human tissue or body fluids. Examples of such devices include, but are not limited to, wound dressings, sealants, tissue fillers, drug delivery systems, coatings, anti-adhesion barriers, catheters, implants, stents, and ophthalmic devices (such as intraocular lenses and contact lenses). A biomedical device can be an ophthalmic device, specifically a contact lens, and most specifically a contact lens made of silicone hydrogel or conventional hydrogel.

[0028] The term "ocular surface" includes the surfaces and glandular epithelial cells of the cornea, conjunctiva, lacrimal gland, accessory lacrimal glands, nasolacrimal duct, and meibomian glands, and their apical and basal matrices, lacrimal puncta, and adjacent or related structures, including the eyelids, which are connected as a functional system by the continuity of epithelial cells, innervation, and the endocrine and immune systems.

[0029] The term "ophthalmic device" refers to any optical device related to the eye and includes devices located in or on the eye or any part of the eye (including the ocular surface). These devices can provide optical correction, cosmetic enhancement, improved vision, therapeutic benefits (such as acting as a bandage), or delivery of active components, such as drug and nutritional formulation components, or a combination of any of the foregoing functions. Examples of ophthalmic devices include, but are not limited to, lenses, optical and ocular inserts (including, but not limited to, punctal plugs, etc.). "Lenses" include spectacle lenses, sunglass lenses, soft contact lenses, rigid contact lenses, hybrid contact lenses, intraocular lenses, and overlay lenses. An ophthalmic device can include a contact lens.

[0030] The term "contact lens" refers to an ophthalmic device that can be placed on the cornea of an individual's eye. Contact lenses can provide corrective, cosmetic, or therapeutic benefits, including wound healing, drug or nutritional agent delivery, diagnostic evaluation or monitoring, ultraviolet light absorption, visible light or glare reduction, or any combination thereof. Contact lenses can be made of any suitable material known in the art and can be soft lenses, hard lenses, or hybrid lenses that include at least two different parts having different physical, mechanical, or optical properties such as modulus, water content, light transmission, or combinations thereof.

[0031] Eyeglass lenses or sunglasses lenses can be made of mineral materials (e.g., silicate-based), or made of organic materials such as polycarbonate; polyamide; polyimide; polysulfone; polyethylene terephthalate / polycarbonate copolymer; and various other materials known in the art.

[0032] The biomedical devices, ophthalmic devices, and lenses of the present invention can be made of silicone hydrogels or conventional hydrogels. Silicone hydrogels generally contain at least one hydrophilic monomer and at least one silicone-containing component that are covalently bonded to each other in the cured device.

[0033] "Target macromolecule" means a macromolecule synthesized from a reactive monomer mixture comprising monomers, macromonomers, prepolymers, crosslinkers, initiators, additives, diluents, etc.

[0034] The term "polymerizable compound" means a compound containing one or more polymerizable groups. This term encompasses, for example, monomers, macromonomers, oligomers, prepolymers, crosslinkers, etc.

[0035] "Polymerizable group" is a group that can undergo chain-growth polymerization (such as free radical and / or cationic polymerization, preferably free radical polymerization), for example, a carbon-carbon double bond that can polymerize when subjected to free radical polymerization initiation conditions. Non-limiting examples of polymerizable groups include (meth)acrylate, styryl, (meth)acrylamide, and vinyl groups. Preferably, the polymerizable group is selected from (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, ethylene carbonate, vinyl ether, vinyl carbamate, and styryl functional groups. More preferably, the polymerizable group is selected from (meth)acrylate and (meth)acrylamide. The polymerizable group can be unsubstituted or substituted. For example, the nitrogen atom in (meth)acrylamide can be bonded to hydrogen, or the hydrogen can be replaced by an alkyl or cycloalkyl group (which itself can be further substituted).

[0036] Any type of free radical polymerization can be used, including but not limited to bulk, solution, suspension, and emulsion, as well as any of the controlled free radical polymerization methods, such as stable free radical polymerization, nitroxide-mediated living polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, organotellurium-mediated living radical polymerization, etc.

[0037] A "monomer" is a monofunctional molecule that can undergo chain-growth polymerization (and specifically free radical polymerization) to form repeating units in the chemical structure of the target macromolecule. Some monomers have difunctional impurities that can act as crosslinking agents. A "hydrophilic monomer" is additionally a monomer that, when mixed with deionized water at a concentration of 5 wt% at 25 °C, produces a clear single-phase solution. A "hydrophilic component" is a monomer, macromonomer, prepolymer, initiator, crosslinking agent, additive, or polymer that, when mixed with deionized water at a concentration of 5 wt% at 25 °C, produces a clear single-phase solution. A "hydrophobic component" is a monomer, macromonomer, prepolymer, initiator, crosslinking agent, additive, or polymer that is slightly soluble or insoluble in deionized water at 25 °C.

[0038] A "macromolecule" is an organic compound with a number average molecular weight greater than 1500 and can be reactive or non-reactive.

[0039] A "macromonomer (macromonomer or macromer)" is a macromolecule having a group that can undergo chain-growth polymerization (and specifically free radical polymerization) to form repeating units in the chemical structure of the target macromolecule. Generally, the chemical structure of the macromonomer is different from that of the target macromolecule. In other words, the repeating units of the side groups of the macromonomer are different from those of the target macromolecule or its main chain. The difference between a monomer and a macromonomer is only one of chemical structure, molecular weight, and the molecular weight distribution of the side groups. Therefore, and as used herein, patent literature occasionally defines a monomer as a polymerizable compound with a relatively low molecular weight of about 1,500 daltons or less, which essentially includes some macromonomers. Specifically, monomethacryloxypropyl-terminated monon-butyl-terminated polydimethylsiloxane (molecular weight = 500 - 1500 g / mol) (mPDMS) and mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated monon-butyl-terminated polydimethylsiloxane (molecular weight = 500 - 1500 g / mol) (OH-mPDMS) can be referred to as monomers or macromonomers. In addition, patent literature occasionally defines a macromonomer as having one or more polymerizable groups, thus essentially expanding the general definition of a macromonomer to include prepolymers. Therefore, and as used herein, difunctional and polyfunctional macromonomers, prepolymers, and crosslinking agents can be used interchangeably.

[0040] ″Silicone-containing component″ is a monomer, macromonomer, prepolymer, crosslinker, initiator, additive or polymer in a reactive mixture that has at least one silicon-oxygen bond, which is typically in the form of a silyloxy group, siloxanyl group, carbosiloxanyl group, and mixtures thereof.

[0041] Examples of silicone-containing components useful in the present invention can be found in U.S. Patent Nos. 3,808,178, 4,120,570, 4,136,250, 4,153,641, 4,740,533, 5,034,461, 5,070,215, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,760,100, 5,849,811, 5,962,548, 5,965,631, 5,998,498, 6,367,929, 6,822,016, 6,943,203, 6,951,894, 7,052,131, 7,247,692, 7,396,890, 7,461,937, 7,468,398, 7,538,146, 7,553,880, 7,572,841, 7,666,921, 7,691,916, 7,786,185, 7,825,170, 7,915,323, 7,994,356, 8,022,158, 8,163,206, 8,273,802, 8,399,538, 8,415,404, 8,420,711, 8,450,387, 8,487,058, 8,568,626, 8,937,110, 8,937,111, 8,940,812, 8,980,972, 9,056,878, 9,125,808, 9,140,825, 9,156,934, 9,170,349, 9,217,813, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929 and European Patent No. 080539. These patents are hereby incorporated by reference in their entirety.

[0042] ″Polymer″ is the target macromolecule composed of repeating units of monomers used during polymerization.

[0043] ″Homopolymer″ is a polymer made from one monomer; ″copolymer″ is a polymer made from two or more monomers; ″terpolymer″ is a polymer made from three monomers. ″Block copolymer″ is composed of compositionally distinct blocks or segments. A diblock copolymer has two blocks. A triblock copolymer has three blocks. ″Comb or graft copolymer″ is made from at least one macromonomer.

[0044] A "repeating unit" is the smallest group of atoms in a polymer that corresponds to the polymerization of a specific monomer or macromonomer.

[0045] An "initiator" is a molecule that can decompose into free radicals, which can then react with monomers to initiate a radical polymerization reaction. Depending on the temperature, thermal initiators decompose at a certain rate; typical examples are azo compounds such as 1,1'-azobisisobutyronitrile and 4,4'-azobis(4-cyanovaleric acid), peroxides such as benzoyl peroxide, tert-butyl peroxide, tert-butyl hydroperoxide, tert-butyl perbenzoate, dicumyl peroxide, and lauroyl peroxide, peracids such as peracetic acid and potassium persulfate, and various redox systems. Photoinitiators that decompose by photochemical methods; typical examples are benzil, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof, as well as derivatives of various monoacyl and bisacyl phosphines and combinations thereof.

[0046] A "crosslinking agent" is a difunctional or polyfunctional monomer or macromonomer that can undergo radical polymerization at two or more positions on the molecule to form branch points and a polymer network. Common examples are ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylenebisacrylamide, triallyl cyanurate, etc.

[0047] A "prepolymer" is the reaction product of monomers that contains remaining polymerizable groups capable of undergoing further reactions to form a polymer.

[0048] A "polymer network" is a crosslinked macromolecule that can swell but not dissolve in a solvent. A "hydrogel" is a polymer network that swells in water or an aqueous solution and usually absorbs at least 10% by weight of water. A "silicone hydrogel" is a hydrogel made from at least one silicone-containing component and at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

[0049] ″Conventional hydrogel″ refers to a polymer network made from components that do not contain any silanyloxy, siloxane, or carbosilane groups. Conventional hydrogels are prepared from a reactive mixture that includes hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate (″HEMA″), N-vinylpyrrolidone (″NVP″), N,N-dimethylacrylamide (″DMA″), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290, and 8,389,597 disclose the formation of conventional hydrogels. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon, and verofilcon, including all their variants.

[0050] ″Silicone hydrogel″ refers to a polymer network made from at least one hydrophilic component and at least one silicone-containing component. Examples of suitable types of hydrophilic components that may be present in the reactive mixture include (meth)acrylates, styrene, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof. Silicone-containing components are well known and have been widely described in the patent literature. For example, a silicone-containing component may include at least one polymerizable group (e.g., (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or a mixture of the foregoing), at least one siloxane group, and one or more linking groups (which may be bonds) that link one or more polymerizable groups to one or more siloxane groups. A silicone-containing component may, for example, contain from 1 to 220 siloxane repeat units. A silicone-containing component may also include at least one fluorine atom. Silicone hydrogel lenses may include a coating, and the coating may be the same or a different material than the substrate.

[0051] Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all their variants, as well as silicone hydrogels prepared as described in U.S. Patent Nos. 4,659,782, 4,659,783, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,998,498, 6,087,415, 5,760,100, 5,776,999, 5,789,461, 5,849,811, 5,965,631, 6,367,929, 6,822,016, 6,867,245, 6,943,203, 7,247,692, 7,249,848, 7,553,880, 7,666,921, 7,786,185, 7,956,131, 8,022,158, 8,273,802, 8,399,538, 8,470,906, 8,450,387, 8,487,058, 8,507,577, 8,637,621, 8,703,891, 8,937,110, 8,937,111, 8,940,812, 9,056,878, 9,057,821, 9,125,808, 9,140,825, 9156,934, 9,170,349, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929, and WO 03 / 22321, WO 2008 / 061992, and US 2010 / 0048847. These patents are hereby incorporated by reference in their entirety.

[0052] ″Interpenetrating polymer network″ includes two or more networks that are at least partially intertwined at the molecular scale but not covalently bonded to each other and cannot be separated without breaking chemical bonds. ″Semi - interpenetrating polymer network″ includes one or more networks and one or more polymers characterized by some mixing at the molecular level between at least one network and at least one polymer. A mixture of different polymers is a ″polymer blend″. Technically, a semi - interpenetrating network is a polymer blend, but in some cases, the polymers are entangled such that they cannot be easily removed.

[0053] The "reactive component" is a polymerizable compound (such as a monomer, macromonomer, oligomer, prepolymer, and crosslinking agent) in a reactive mixture (defined below), as well as any other component in the reactive mixture that is intended to remain substantially in the resulting polymer network after polymerization and all post-treatment steps (such as extraction steps) and packaging steps have been completed. The reactive component can be retained in the polymer network by covalent bonding, hydrogen bonding, electrostatic interaction, formation of an interpenetrating polymer network, or any other means. Components intended to be released from the polymer network are still considered "reactive components" when in use. For example, a drug component or nutritional component in a contact lens that is intended to be released during wear is considered a "reactive component". Components such as diluents that are intended to be removed from the polymer network during the manufacturing process (e.g., by extraction) are not "reactive components".

[0054] The terms "reactive mixture" and "reactive monomer mixture" refer to a mixture of components that are mixed together and, when subjected to polymerization conditions, result in the formation of a polymer network (such as a conventional hydrogel or a silicone hydrogel), as well as biomedical devices, ophthalmic devices, and contact lenses made therefrom. The reactive mixture can contain reactive components (such as monomers, macromonomers, prepolymers, crosslinking agents, and initiators), additives (such as wetting agents), polymers, dyes, light-absorbing compounds (such as UV absorbers), pigments, photochromic compounds, pharmaceutical compounds, and / or nutritional compounds, any of which can be polymerizable or non-polymerizable but capable of remaining in the resulting biomedical device (such as a contact lens). The reactive mixture can also contain other components that are intended to be removed from the device before use, such as diluents. It should be understood that a wide range of additives can be added based on the contact lens being made and its intended use. The concentration of the components of the reactive mixture is expressed as a weight percentage of all the reactive components in the reactive mixture (thus excluding diluents). When diluents are used, their concentration is expressed as a weight percentage based on the amount of all the components in the reactive mixture (including diluents).

[0055] The term "silicone hydrogel contact lens" refers to a hydrogel contact lens made from at least one silicone-containing compound. Compared to conventional hydrogels, silicone hydrogel contact lenses generally have improved oxygen permeability. Silicone hydrogel contact lenses utilize both their water and polymer contents to transport oxygen to the eye.

[0056] The term "polyfunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having one polymerizable group.

[0057] The term "halogen" or "halo group" indicates fluorine, chlorine, bromine, and iodine.

[0058] ″Alkyl″ means an optionally substituted straight-chain or branched alkyl group containing a specified number of carbon atoms. If the number is not specified, the alkyl group (including any optional substituents on the alkyl) may contain from 1 to 16 carbon atoms. Preferably, the alkyl group contains from 1 to 10 carbon atoms, alternatively from 1 to 8 carbon atoms, alternatively from 1 to 6 carbon atoms, or alternatively from 1 to 4 carbon atoms. Examples of alkyl include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, etc. Examples of substituents on the alkyl include one, two or three groups independently selected from the following: hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. ″Alkylene″ means a divalent alkyl group, such as -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH)3CH2- and -CH2CH2CH2CH2-.

[0059] ″Haloalkyl″ means an alkyl group as defined above substituted with one or more halogen atoms, where each halogen is independently F, Cl, Br or I. The preferred halogen is F. Preferred haloalkyl groups contain from 1 to 6 carbons, more preferably from 1 to 4 carbons, and still more preferably from 1 to 2 carbons. ″Haloalkyl″ includes perhaloalkyl groups, such as -CF3- or -CF2CF3-. ″Haloalkylene″ means a divalent haloalkyl group, such as -CH2CF2-.

[0060] ″Cycloalkyl″ means an optionally substituted cyclic hydrocarbon containing a specified number of ring carbon atoms. If the number is not indicated, the cycloalkyl may contain from 3 to 12 ring carbon atoms. Preferred are C3-C8 cycloalkyl groups, C3-C7 cycloalkyl, more preferably C4-C7 cycloalkyl, and still more preferably C5-C6 cycloalkyl. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Examples of substituents on the cycloalkyl include one, two or three groups independently selected from the following: alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, alkylthio, amido, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. ″Cycloalkylene″ means a divalent cycloalkyl group, such as 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene.

[0061] ″Heterocycloalkyl″ means a cycloalkyl ring or ring system as defined above in which at least one ring carbon has been replaced by a heteroatom selected from nitrogen, oxygen and sulfur. The heterocycloalkyl ring is optionally fused to or otherwise connected to other heterocycloalkyl rings and / or non-aromatic hydrocarbon rings and / or benzene rings. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 or 6 members. Heterocycloalkylene means a divalent heterocycloalkyl group.

[0062] "Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. An aryl group contains a specified number of ring carbon atoms. If no number is indicated, an aryl may contain 6 to 14 ring carbon atoms. The aromatic rings may be optionally fused or otherwise attached to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings. Examples of aryl groups include phenyl, naphthyl, and biphenyl. Preferred examples of aryl groups include phenyl. Examples of substituents on the aryl include one, two, or three groups independently selected from the following: alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Arylene" means a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene, or 1,4-phenylene.

[0063] "Heteroaryl" refers to an aryl ring or ring system as defined above in which at least one ring carbon atom has been replaced by a heteroatom selected from nitrogen, oxygen, and sulfur. Heteroaryl rings may be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings, or heterocycloalkyl rings. Examples of heteroaryl groups include pyridyl, furyl, and thienyl. "Heteroarylene" means a divalent heteroaryl group.

[0064] "Alkoxy" refers to an alkyl group attached to the parent molecular moiety by an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy, and isopropoxy. "Alkylthio" means an alkyl group attached to the parent molecule by a sulfur bridge. Examples of alkylthio groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" refers to an aryl group attached to the parent molecular moiety by an oxygen bridge. Examples include phenoxy. "Cycloalkoxy" means a cycloalkyl group attached to the parent moiety by an oxygen bridge.

[0065] "Alkylamine" refers to an alkyl group attached to the parent molecular moiety by an -NH bridge. Alkyleneamine means a divalent alkylamine group, such as -CH2CH2NH-.

[0066] "Siloxanyl" refers to a structure having at least one Si-O-Si bond. Thus, for example, a siloxanyl group means a group having at least one Si-O-Si group (i.e., a siloxanyl group), and a siloxanyl compound means a compound having at least one Si-O-Si group. "Siloxanyl" encompasses monomers (e.g., Si-O-Si) as well as oligomeric / polymeric structures (e.g., -[Si-O] n -, where n is 2 or greater). Each silicon atom in the siloxanyl group is replaced by an independently selected R A group (where R A is defined as in options (b) to (i) of formula A) to complete its valence.

[0067] ″Silyl″ refers to a structure of the formula R3Si-, and ″silyloxy″ refers to a structure of the formula R3Si-O-, where each R in the silyl or silyloxy independently is selected from trimethylsilyloxy, C1-C8 alkyl (preferably C1-C3 alkyl, more preferably ethyl or methyl), and C3-C8 cycloalkyl.

[0068] ″Alkyleneoxy″ refers to a group having the general formula -(alkylene - O -) p - or -(O - alkylene) p -, where alkylene is as defined above, and p is from 1 to 200, or 1 to 100, or 1 to 50, or 1 to 25, or 1 to 20, or 1 to 10, where each alkylene is independently optionally substituted with one or more groups independently selected from hydroxy, halo (such as fluorine), amino, amido, ether, carbonyl, carboxyl, and combinations thereof. If p is greater than 1, each alkylene may be the same or different, and the alkyleneoxy may be in a block or random configuration. When the alkyleneoxy forms a terminal group in the molecule, the terminus of the alkyleneoxy may be, for example, hydroxy or alkoxy (such as HO - [CH2CH2O] p - or CH3O - [CH2CH2O] p -). Examples of alkyleneoxy include poly(ethyleneoxy), poly(propyleneoxy), poly(butyleneoxy), and poly(ethyleneoxy - co - propyleneoxy).

[0069] ″Oxaalkylene″ refers to an alkylene group as defined above, where one or more non - adjacent CH2 groups have been replaced by oxygen atoms, such as -CH2CH2OCH(CH3)CH2-. ″Thiaalkylene″ refers to an alkylene group as defined above, where one or more non - adjacent CH2 groups have been replaced by sulfur atoms, such as -CH2CH2SCH(CH3)CH2-.

[0070] The term "linking group" refers to the moiety that attaches a polymerizable group to the parent molecule. The linking group can be any moiety that is compatible with the compound, is part of the compound and does not undesirably interfere with the polymerization of the compound, and is stable under the polymerization conditions and the conditions for processing and storing the final product. For example, the linking group can be a bond, or it can include one or more alkylene, haloalkylene, amide, amine, alkyleneamine, carbamate, ester (-CO2-), arylene, heteroarylene, cycloalkylene, heterocycloalkylene, alkoxy, oxaalkylene, thiaalkylene, haloalkoxy (alkoxy substituted with one or more halo groups, such as -OCF2-, -OCF2CF2-, -OCF2CH2-), siloxanyl, siloxaalkylene, or combinations thereof. The linking group can be optionally substituted with one or more substituent groups. Suitable substituent groups can include those independently selected from alkyl, halogen (such as fluorine), hydroxy, HO-alkoxy, MeO-alkoxy, siloxanyl, silyloxy, silyloxy-alkoxy-, silyloxy-alkylene-alkoxy- (wherein more than one alkoxy group can be present, and wherein each methylene in the alkylene and alkoxy is independently optionally substituted with hydroxy), ether, amine, carbonyl, carbamate, and combinations thereof. The linking group can also be substituted with a polymerizable group such as (meth)acrylate (in addition to the polymerizable group to which the linking group is attached).

[0071] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene), C1-C8 oxaalkylene (preferably C2-C6 oxaalkylene), C1-C8 thiaalkylene, C1-C8 alkylene-carboxylate-C1-C8 alkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene, each of which is optionally substituted with one or two groups independently selected from hydroxy and siloxy.

[0072] When the linking group is composed of a combination of moieties as described above (e.g., alkylene and cycloalkylene), the moieties can be present in any order. For example, if in formula A below, L is indicated as -alkylene-cycloalkylene-, then Rg-L can be Rg-alkylene-cycloalkylene- or Rg-cycloalkylene-alkylene-. Nevertheless, the listed order indicates the preferred order of the moieties as they appear in the compound starting from the terminal polymerizable group (Rg or Pg) to which the linking group is attached. For example, if in formula A, L is indicated as -alkylene-cycloalkylene-, then Rg-L is preferably Rg-alkylene-cycloalkylene-.

[0073] The term "electron-withdrawing group" (EWG) refers to a chemical group that withdraws electron density from the atom or group of atoms to which it is attached. Examples of EWGs include, but are not limited to, cyano, amide, ester, keto or aldehyde. A preferred EWG is cyano (CN).

[0074] The term "light-absorbing compound" refers to a chemical material that absorbs light within the visible spectrum (e.g., in the range of 380 nm to 780 nm). "High-energy radiation absorber", "UV / HEV absorber" or "high-energy light-absorbing compound" are chemical materials that absorb ultraviolet light, high-energy visible light or both at various wavelengths. The ability of a material to absorb light at certain wavelengths can be determined by measuring its ultraviolet / visible transmission or absorption spectrum.

[0075] When the compounds described herein contain an olefinic double bond or other geometrically asymmetric center, and unless otherwise specified, the compound is intended to include cis, trans, Z- and E-configurations. Similarly, all tautomeric and salt forms are also intended to be included.

[0076] The term "optional substituent" means that a hydrogen atom in the following moiety is optionally replaced by a substituent. Any substituent that has steric utility at the substitution site and is synthetically feasible can be used. The identification of suitable optional substituents is entirely within the ability of one of ordinary skill in the art. Examples of "optional substituents" include, but are not limited to, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halo, hydroxy, amino, NR 4 R 5 、benzyl, SO3H, SO3Na or -Y-P g wherein R 4 and R 5 are independently H or C1-C6 alkyl, Y is a linking group; and P g is a polymerizable group. The foregoing substituents may optionally be substituted by optional substituents (which are preferably not further substituted unless otherwise specified). For example, an alkyl group may be substituted by a halo group (e.g., to produce CF3).

[0077] "Substructure" means the chemical structure of a compound and any compound derived from that chemical structure by replacing one or more hydrogen atoms with any other atom (which may be bonded to other atoms or groups). For example, one or more hydrogen atoms may be replaced by independently selected optional substituents, preferably 1, 2 or 3, more preferably 1 or 2, more preferably 1 hydrogen atom. Included within the definition of "substructure" are materials in which the substructure forms a fragment of a larger compound, such as a monomer (e.g., containing one or more polymerizable groups), a polymer or a macromolecule.

[0078] "Maximum visible light absorption" means the wavelength within the visible light wavelength range (380 nm to 760 nm) at which the absorbance is at a maximum. This definition encompasses materials that exhibit an overall absorption maximum outside the visible light range (such as within the UV region).

[0079] The terms "light stable", "light stability", or similar expressions mean that a compound (optionally embedded in an ophthalmic device, such as a hydrogel contact lens, when measured, and optionally measured inside or outside a blister pack or vial) exhibits an absorbance loss of no more than 20% at the maximum visible light absorption after exposure to light under conditions such as those in the "ICH Harmonized Tripartite Guideline: Q1B Photostability Testing of New Drug Substances and Products", published in November 1996. Preferably, under the ICH photostability guideline, using Option 2 light source, preferably in a photostability chamber controlled at 25 °C / Amb RH, with an estimated light exposure of 1.5192×10 6 Lux hours (168.8 hours exposure time) and an estimated UV irradiation exposure of 259.4 watt - hours / m 2 (16.2 hours exposure time) for exposure. After exposure, the UV / Vis spectrum of the sample is collected and compared with the spectrum of the sample before exposure. The change relative to the maximum visible light absorption of the lens observed before exposure is calculated. By way of example, if the absorbance at the maximum visible light absorption before exposure is 4 absorbance units and after exposure is 2 absorbance units, the absorbance loss is 50%. In the present invention, the absorbance loss after light exposure is preferably no more than 15%, or no more than 10%, or no more than 7%, or no more than 5%, or no more than 4%, or no more than 3%, or no more than 2%, or no more than 1%, or no more than 0.5%, or no more than 0.1%.

[0080] The term "more light - stable than macular pigment" or similar expressions mean that a compound (optionally embedded in an ophthalmic device, such as a hydrogel contact lens, when tested, and optionally measured inside or outside a blister pack) exhibits less absorbance loss at the maximum visible light absorption after exposure to light under, for example, the ICH photostability guideline as described above, than that observed with macular pigment.

[0081] The term full width at half maximum (FWHM) means the width of an absorption peak at half of its maximum intensity.

[0082] The terms "thermally stable", "thermal stability", or similar expressions mean that a compound (which may optionally be incorporated into an ophthalmic device, such as a hydrogel contact lens, and optionally measured inside or outside a blister pack or vial when measured) exhibits an absorbance loss of no more than 20% at the maximum visible light absorbance after being exposed in a stability chamber at 89 °C for one month as described in the following examples. After exposure, the ultraviolet / visible spectrum of the sample is collected and compared with the spectrum of the sample before exposure. The change relative to the maximum visible light absorbance of the lens observed before exposure is calculated. By way of example, if the absorbance at the maximum visible light absorbance before exposure is 4 absorbance units and 2 absorbance units after exposure, the absorbance loss is 50%. In the present invention, the absorbance loss after thermal exposure is preferably no more than 20%, or no more than 15%, or no more than 12%, or no more than 10%, or no more than 5%, or no more than 4%, or no more than 3%, or no more than 2%, or no more than 1%, or no more than 0.5%, or no more than 0.1%.

[0083] The term "more thermally stable than macular pigment" or similar expressions mean that a compound (which may optionally be incorporated into an ophthalmic device, such as a hydrogel contact lens, and optionally measured inside or outside a blister pack when tested) exhibits less absorbance loss at the maximum visible light absorbance after the thermal exposure as described above than that observed with macular pigment.

[0084] Unless otherwise specified, ratios, percentages, parts, etc. are by weight.

[0085] Unless otherwise specified, numerical ranges, such as in "2 to 10" or in "between 2 and 10", include the numbers defining the range (e.g., 2 and 10).

[0086] As described above, in one aspect, the present invention provides compounds that substantially mimic the visible light absorption characteristics of macular pigment. The compounds are more photostable than macular pigment and can thus be used in the manufacture of products. For example, the compounds can be used in ophthalmic devices.

[0087] Thus, the compounds of the present invention may have a maximum visible light absorbance between 430 nm and 480 nm and a full width at half maximum (FWHM) at the maximum visible light absorbance of at least 35 nm and at most 150 nm. The compound may be photostable (e.g., when measured according to ICH guideline Q1B). The compound may be more photostable than macular pigment.

[0088] The compound may have a maximum visible light absorbance between 440 nm and 480 nm, or between 450 nm and 475 nm, or between 455 nm and 475 nm, or between 460 nm and 470 nm.

[0089] The compound can exhibit an FWHM of at least 35 nm, or at least 40 nm, or at least 45 nm, or at least 55 nm, or at least 60 nm at the visible light absorption maximum. The compound can exhibit an FWHM of at most 125 nm, or at most 100 nm, or at most 95 nm, or at most 90 nm, or at most 85 nm, or at most 80 nm, or at most 75 nm, or at most 70 nm at the visible light absorption maximum. The FWHM at the visible light absorption maximum can be in the range of 35 nm to 150 nm, or 35 nm to 100 nm, or 45 nm to 90 nm, or 55 nm to 80 nm, or 60 nm to 75 nm, or 60 nm to 70 nm, or 62 nm to 67 nm.

[0090] The compounds of the present invention can exhibit a molar extinction coefficient of at least 5000, or at least 5500, or at least 6000, or at least 6500, or at least 7000, or at least 7500, or at least 7740, or at least 7800, or at least 8000, or at least 9000, or at least 10,000, or at least 11,000, or at least 12,000, or at least 12,500 at the visible light absorption maximum. The molar extinction coefficient is an inherent property of the material and can be calculated from absorbance data using Beer-Lambert's law. The unit is usually L.mol -1 .cm -1 。

[0091] The compounds of the present invention may include a chromophore having a substructure of formula I:

[0092]

[0093] wherein EWG is an electron-withdrawing group, and the compound has a visible light absorption maximum in the range of 440 nm to 480 nm, or 450 nm to 475 nm, or 460 nm to 470 nm. EWG can be cyano, amide, ester, keto or aldehyde. Preferably, EWG is cyano.

[0094] The compounds of the present invention may have formula II:

[0095]

[0096] wherein m and n are independently 0, 1, 2, 3 or 4; T is a bond, O or NR 6 , wherein R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or Y-P g ; R is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Y is a linking group; P g is a polymerizable group; when R is present1 and R 2 , which is independently, each time it appears, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 thioalkyl group, a C3-C7 cycloalkyl group, an aryl group (preferably unsubstituted phenyl or phenyl substituted by an alkyl or halo group), a halo group, a hydroxyl group, an amino group, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation such as sodium or potassium), wherein R 3 and R 4 are independently H or a C1-C6 alkyl group, or two adjacent R 1 or R 2 groups, and the two adjacent groups combine with the carbon atom to which they are attached to form a cycloalkyl or aryl ring; and EWG is an electron-withdrawing group.

[0097] The compound of formula II preferably contains one or two Y-P g groups. More preferably, the compound contains one Y-P g group.

[0098] The compound of formula II may include a compound of formula II-1, which is a compound of formula II wherein m and n are independently 0 or 1 or alternatively both are 0.

[0099] The compounds of formula II and formula II-1 may include a compound of formula II-2, which is a compound of formula II or formula II-1 wherein n is 0 and m is 1.

[0100] The compounds of formula II, formula II-1 and formula II-2 may include a compound of formula II-3, which is a compound of formula II, formula II-1 or formula II-2 wherein n is 0, m is 1 and R 1 is a C1-C6 alkyl group or a C1-C6 alkoxy group.

[0101] The compounds of formula II, formula II-1, formula II-2 and formula II-3 may include a compound of formula II-4, which is a compound of formula II, formula II-1, formula II-2 or formula II-3 wherein R is H, or a C1-C6 alkyl group. Preferably, R is a C1-C6 alkyl group.

[0102] The compounds of formula II, formula II-1, formula II-2, formula II-3 and formula II-4 may include a compound of formula II-5, which is a compound of formula II, formula II-1, formula II-2, formula II-3 or formula II-4 wherein T is NR 6 and R 6 is H or a C1-C6 alkyl group. Preferably, R6 is H.

[0103] Compounds of Formula II, Formula II-1, Formula II-2, Formula II-3, Formula II-4, and Formula II-5 may include a compound of Formula II-6, which is a compound wherein P g (polymerizable group) is independently, in each occurrence, styryl, ethylene carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide in a compound of Formula II, Formula II-1, Formula II-2, Formula II-3, Formula II-4, or Formula II-5. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents, and other components commonly used in the manufacture of polymeric devices. The compatibility of the compound with the reactive mixture can be controlled by selecting the polymerizable group (and the linking group). Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferred polymerizable group is methacrylate.

[0104] Compounds of Formula II, Formula II-1, Formula II-2, Formula II-3, Formula II-4, Formula II-5, and Formula II-6 may include a compound of Formula II-7, which is a compound wherein Y (linking group) is alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination of any of the above groups in a compound of Formula II, Formula II-1, Formula II-2, Formula II-3, Formula II-4, Formula II-5, and Formula II-6. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propylene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred is C1-C8 alkylene, especially ethylene (-CH2CH2-). When T in the compound of Formula II is O, it is preferred to hinder the carbon atom of the linking group to which O is attached. For example, if T is O and Y is alkylene, the preferred alkylene is -C(R H )2(CH-2) x -, wherein R H is independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is from 1 to 5.

[0105] Compounds of Formula II, Formula II-1, Formula II-2, Formula II-3, Formula II-4, Formula II-5, Formula II-6, and Formula II-7 may include a compound of Formula II-8, which is a compound wherein T is a bond or NR 6Compounds of formula II, formula II-1, formula II-2, formula II-3, formula II-4, formula II-5, formula II-6 or formula II-7 (preferably NH).

[0106] Compounds of formula II, formula II-1, formula II-2, formula II-3, formula II-4, formula II-5, formula II-6, formula II-7 and formula II-8 may include compounds of formula II-9, which are compounds of formula II, formula II-1, formula II-2, formula II-3, formula II-4, formula II-5, formula II-6, formula II-7 or formula II-8 in which EWG is cyano, amide, ester, keto or aldehyde. Preferably, EWG is cyano.

[0107] The compounds of the present invention may have formula III:

[0108]

[0109] Wherein:

[0110] T is a bond, O or NR 6 , where R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0111] R is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0112] Y is a linking group;

[0113] P g is a polymerizable group;

[0114] R 7 is H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halogen), halogen, hydroxy, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation such as sodium or potassium), where R 3 and R 4 are independently H or C1-C6 alkyl; and

[0115] EWG is an electron-withdrawing group.

[0116] Compounds of formula III may include compounds of formula III-1, which are compounds of formula III in which R 7 is H.

[0117] Compounds of formula III may include compounds of formula III-2, which are compounds of formula III in which R 7A compound of formula III which is a C1-C6 alkyl, C1-C6 alkoxy or C1-C6 thioalkyl.

[0118] Compounds of formula III and formula III-2 may include compounds of formula III-3, which are compounds of formula III-3 wherein R 7 A compound of formula III or formula III-2 which is a C1-C6 alkoxy (such as ethoxy or methoxy, preferably methoxy).

[0119] Compounds of formula III, formula III-1, formula III-2 and formula III-3 may include compounds of formula III-4, which are compounds of formula III, formula III-1, formula III-2 or formula III-3 wherein R is H, or a C1-C6 alkyl. Preferably, R is a C1-C6 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl or sec-butyl. Preferably, R is n-propyl or n-butyl.

[0120] Compounds of formula III, formula III-1, formula III-2, formula III-3 and formula III-4 may include compounds of formula III-5, which are compounds of formula III, formula III-1, formula III-2, formula III-3 or formula III-4 wherein T is NR 6 and R 6 is H or a C1-C6 alkyl. Preferably, R 6 is H.

[0121] Compounds of formula III, formula III-1, formula III-2, formula III-3, formula III-4 and III-5 may include compounds of formula III-6, which are compounds of formula III, formula III-1, formula III-2, formula III-3, formula III-4 or III-5 wherein P g (polymerizable group) independently includes styryl, ethylene carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate or (meth)acrylamide each time it appears. Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. A more preferred polymerizable group is methacrylate.

[0122] Compounds of Formula III, Formula III-1, Formula III-2, Formula III-3, Formula III-4, Formula III-5, and Formula III-6 may include a compound of Formula III-7, which is a compound of Formula III, Formula III-1, Formula III-2, Formula III-3, Formula III-4, Formula III-5, and Formula III-6 in which Y (linking group) is alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination of any of the foregoing groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propylene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred is C1-C8 alkylene, especially ethylene (-CH2CH2-). When T in the compound of Formula III is O, it is preferred to hinder the carbon atom of the linking group to which O is attached. For example, if T is O and Y is alkylene, the preferred alkylene is -C(R H )2(CH-2) x -, where R H is independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is from 1 to 5.

[0123] Compounds of Formula III, Formula III-1, Formula III-2, Formula III-3, Formula III-4, Formula III-5, Formula III-6, and Formula III-7 may include a compound of Formula III-8, which is a compound of Formula III, Formula III-1, Formula III-2, Formula III-3, Formula III-4, Formula III-5, Formula III-6, or Formula III-7 in which T is a bond or is NR 6 (preferably NH).

[0124] Compounds of Formula III, Formula III-1, Formula III-2, Formula III-3, Formula III-4, Formula III-5, Formula III-6, Formula III-7, and Formula III-8 may include a compound of Formula III-9, which is a compound of Formula III, Formula III-1, Formula III-2, Formula III-3, Formula III-4, Formula III-5, Formula III-6, Formula III-7, or Formula III-8 in which EWG is cyano, amide, ester, keto, or aldehyde. Preferably, EWG is cyano.

[0125] Specific examples of the compounds of the present invention are shown in Table A.

[0126] Table A

[0127]

[0128] The compounds of the present invention can be prepared via the Knoevenagel condensation of N-substituted acridones to form acridinylidene derivatives with active methylene derivatives. Although the condensation with malononitrile is carried out at high temperature in the presence of a weaker electrophile such as acetic anhydride, the reaction with a weaker nucleophile such as 2,4-diketone, 2-cyanoacetamide, and 2-cyanoacetate derivatives may not form the desired product. Such transformations generally require a combination of a strong Lewis acid such as titanium(IV) chloride, or a strong electrophile such as thionyl chloride and high temperature to form a reactive intermediate capable of undergoing the reaction. The known methods using titanium(IV) chloride or thionyl chloride at high temperature require a large excess of reagents, have poor selectivity, and low yields of the desired product. Stoichiometric control of the electrophile and / or mild reaction conditions can contribute to improving the overall selectivity and product yield.

[0129] In one aspect of the present invention, an improved method for synthesizing acridinylidene derivatives (such as the above compounds) from N-substituted acridones is provided. The method uses triphenylphosphine dibromide. Triphenylphosphine dibromide can be generated "in situ" by adding bromine to triphenylphosphine in a suitable solvent. Adding the N-substituted acridone after the bromine is completely consumed avoids the potential oxidation of the N-substituted acridone and forms the desired product in high yield while significantly reducing the formation of by-products. An exemplary synthesis of the compound of formula II is shown in Scheme A.

[0130]

[0131] The compounds of the present invention can be used in combination with other light-absorbing compounds to provide the desired absorption characteristics. For example, a preferred composition can contain the compounds described herein together with a UV-absorbing compound. Suitable UV-absorbing compounds are known in the art and are divided into several classes, including but not limited to benzophenone, benzotriazole, triazine, substituted acrylonitrile, salicylic acid derivatives, benzoic acid derivatives, cinnamic acid derivatives, chalcone derivatives, benzilidineacetone derivatives, crotonic acid derivatives, or any mixture thereof. A preferred class of UV-absorbing compounds is benzotriazole, such as Norbloc (2-(2'-hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole).

[0132] The compounds of the present invention can be included in a reactive mixture to form various products, including biomedical devices and ophthalmic devices. The compounds can, for example, be incorporated into the device and / or they can be coated on the surface of the device. When incorporated into the device, the compounds can generally be added to the reactive mixture used to prepare the device and can be present in any amount up to their solubility limit. For example, the compounds can be present at a concentration of at least 0.1% or at least 2%; and at most 10% or at most 5%, based on the weight percentage of all components (excluding diluents) in the reaction mixture. Typical concentrations can be in the range of 1% to 5%. The upper limit is generally determined by the solubility of the compound with other comonomers and / or diluents in the reactive monomer mixture.

[0133] Preferably, the compounds of the present invention are included in ophthalmic devices. A variety of ophthalmic devices can be prepared, including spectacle lenses, sunglass lenses, rigid contact lenses, soft contact lenses, corneal inlays, corneal implants, intraocular lenses or overlay lenses. Preferably, the ophthalmic device is an intraocular lens or a soft contact lens. Soft contact lenses can be made from conventional (non-silicone) hydrogels or from silicone hydrogels.

[0134] The ophthalmic devices of the present invention can comprise the free radical reaction product of a reactive mixture containing one or more monomers suitable for making the desired ophthalmic device (also referred to herein as device-forming monomers or hydrogel-forming monomers) and optional components. When polymerized, the reactive mixture results in the formation of a polymer network, and the ophthalmic device can comprise this polymer network. The polymer network can, for example, be a hydrogel (e.g., a conventional hydrogel or a silicone hydrogel).

[0135] The compounds of the present invention can copolymerize with other components in the reactive mixture, in which case, in addition to one or more monomers suitable for making the desired ophthalmic device (and any optional components), the reactive mixture can further comprise one or more of the compounds of the present invention.

[0136] Non-limiting examples of polymer networks in which the compounds of the present invention can be incorporated (e.g., as monomers) are as described above and include, for example, etafilcon, genfilcon, hilafilcon, lenfilcon, nesofilcon, omafilcon, polymacon, verofilcon, acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all their variants.

[0137] By additional example, the polymer network can be made from a reactive mixture that contains one or more of the following: a hydrophilic component, a hydrophobic component, a silicone-containing component, a wetting agent (such as a polyamide), a crosslinking agent, and other components (such as diluents and initiators). As described above, the reactive mixture can also contain one or more compounds of the present invention.

[0138] Hydrophilic Component

[0139] Examples of suitable types of hydrophilic monomers that can be present in the reactive mixture include (meth)acrylates, styrene, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

[0140] Non-limiting examples of hydrophilic (meth)acrylate and (meth)acrylamide monomers include: acrylamide, N-isopropylacrylamide, N,N-dimethylaminopropyl (meth)acrylamide, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N-(2-hydroxyethyl) (meth)acrylamide, N,N-bis(2-hydroxyethyl) (meth)acrylamide, N-(2-hydroxypropyl) (meth)acrylamide, N,N-bis(2-hydroxypropyl) (meth)acrylamide, N-(3-hydroxypropyl) (meth)acrylamide, N-(2-hydroxybutyl) (meth)acrylamide, N-(3-hydroxybutyl) (meth)acrylamide, N-(4-hydroxybutyl) (meth)acrylamide, 2-aminoethyl (meth)acrylate, 3-aminopropyl (meth)acrylate, 2-aminopropyl (meth)acrylate, N-2-aminoethyl (meth)acrylamide, N-3-aminopropyl (meth)acrylamide, N-2-aminopropyl (meth)acrylamide, N,N-bis-2-aminoethyl (meth)acrylamide, N,N-bis-3-aminopropyl (meth)acrylamide, N,N-bis-2-aminopropyl (meth)acrylamide, glycerol methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.

[0141] The hydrophilic monomer can also be ionic, including anionic, cationic, zwitterionic, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropionic acid (ACA1), 5-acrylamidopropionic acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propanaminium inner salt (CBT), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propanaminium inner salt (SBT), 4-hydroxy-N,N,N-trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phosphaundec-10-en-1-aminium inner salt (9CI) (PBT), 2-methacryloyloxyethylphosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), and (methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0142] Non-limiting examples of hydrophilic N-vinyl lactam and N-vinyl amide monomers include: N-vinyl pyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinyl acetamide (NVA), N-vinyl-N-methyl acetamide (VMA), N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl-N-methyl propionamide, N-vinyl-N-methyl-2-methyl propionamide, N-vinyl-2-methyl propionamide, N-vinyl-N,N'-dimethyl urea, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl isopropyl amide, N-vinyl caprolactam, N-vinyl imidazole, and mixtures thereof.

[0143] Non-limiting examples of hydrophilic O-vinyl carbamate and O-vinyl carbonate monomers include N-2-hydroxyethyl vinyl carbamate and N-carboxy-β-alanine N-vinyl ester. Other examples of hydrophilic ethylene carbonate or vinyl carbamate monomers are disclosed in U.S. Patent 5,070,215. Hydrophilic oxazolone monomers are disclosed in U.S. Patent 4,910,277.

[0144] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyl oxazoline.

[0145] The hydrophilic monomer can also be a linear or branched macromonomer or prepolymer of poly(ethylene glycol), poly(propylene glycol), or a statistical random or block copolymer of ethylene oxide and propylene oxide, which has polymerizable moieties such as (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinyl amide, etc. These macromonomers of polyethers have one polymerizable group; the prepolymers can have two or more polymerizable groups.

[0146] Preferred hydrophilic monomers of the present invention are DMA, NVP, HEMA, VMA, NVA, and mixtures thereof. Preferred hydrophilic monomers include a mixture of DMA and HEMA. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

[0147] Generally, there is no particular limitation on the amount of hydrophilic monomer present in the reactive monomer mixture. The amount of hydrophilic monomer can be selected based on the desired characteristics of the resulting hydrogel, including water content, light transmittance, wettability, protein absorption, etc. Wettability can be measured by contact angle, and the desired contact angle is less than about 100°, less than about 80°, and less than about 60°. Based on the total weight of the reactive components in the reactive monomer mixture, the hydrophilic monomer can be present, for example, in an amount in the range of about 0.1 wt% to about 100 wt%, alternatively in the range of about 1 wt% to about 80 wt%, alternatively in the range of about 5 wt% to about 65 wt%, alternatively in the range of about 40 to about 60 wt%, or alternatively in the range of about 55 wt% to about 60 wt%.

[0148] Silicone-Containing Component

[0149] The silicone-containing component suitable for the present invention comprises one or more polymerizable compounds, wherein each compound independently comprises at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting the one or more polymerizable groups to the one or more siloxane groups. The silicone-containing component can, for example, contain 1 to 220 siloxane repeating units, such as the groups defined below. The silicone-containing component can also comprise at least one fluorine atom.

[0150] The silicone-containing component can comprise: one or more polymerizable groups as defined above; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units. The silicone-containing component can comprise: one or more polymerizable groups, which are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0151] The silicone-containing component may comprise: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, styryl or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that link the polymerizable groups to the siloxane units.

[0152] The silicone-containing component may comprise: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that link the polymerizable groups to the siloxane units.

[0153] The silicone-containing component may comprise one or more polymerizable compounds of formula A:

[0154]

[0155] Wherein:

[0156] At least one R A Is a group of formula R g -L-, where R g Is a polymerizable group, and L is a linking group, and the remaining Rs A Are each independently:

[0157] (a) R g -L-,

[0158] (b) A C1-C 16 Alkyl group optionally substituted by one or more hydroxyl, amino, amido, oxa, carboxyl, alkyl carboxyl, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl or combinations thereof,

[0159] (c) A C3-C 12 Cycloalkyl group optionally substituted by one or more alkyl, hydroxyl, amino, amido, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl or combinations thereof,

[0160] (d) A C6-C 14 Aryl group optionally substituted by one or more alkyl, hydroxyl, amino, amido, oxa, carboxyl, alkyl carboxyl, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl or combinations thereof,

[0161] (e) Halo,

[0162] (f) Alkoxy, cyclic alkoxy or aryloxy,

[0163] (g) Silanyloxy,

[0164] (h) Alkanoxy-alkyl or alkoxy-alkanoxy-alkyl, such as poly(ethyleneoxy)alkyl, poly(propyleneoxy)alkyl or poly(ethyleneoxy-co-propyleneoxy)alkyl, or

[0165] (i) A monovalent siloxane chain containing 1 to 100 siloxane repeating units, the siloxane repeating units being optionally substituted by alkyl, alkoxy, hydroxy, amino, oxa, carboxy, alkylcarboxy, alkoxy, amido, carbamate, halogen or combinations thereof; and

[0166] n is from 0 to 500, or from 0 to 200, or from 0 to 100, or from 0 to 20, it being understood that when n is not 0, n is a distribution having a mode equal to the specified value. When n is 2 or greater, the SiO units may bear the same or different R A substituents, and if different R A substituents are present, the n groups may be in a random or block configuration.

[0167] In formula A, the three R A may each contain a polymerizable group, alternatively two R A may each contain a polymerizable group, or alternatively one R A may contain a polymerizable group.

[0168] Examples of silicone-containing components suitable for the present invention include, but are not limited to, the compounds listed in Table B. The compounds in Table B contain polysiloxane groups, and unless otherwise specified, the number of SiO repeating units in such compounds is preferably from 3 to 100, more preferably from 3 to 40, or still more preferably from 3 to 20.

[0169] Table B

[0170]

[0171]

[0172] Additional non-limiting examples of suitable silicone-containing components are listed in Table C. Unless otherwise specified, where applicable, j2 is preferably from 1 to 100, more preferably from 3 to 40, or still more preferably from 3 to 15. In compounds containing j1 and j2, the sum of j1 and j2 is preferably from 2 to 100, more preferably from 3 to 40, or still more preferably from 3 to 15.

[0173] Table C

[0174]

[0175]

[0176] Mixtures of components containing silicone may be used. By way of example, suitable mixtures may include, but are not limited to: mixtures of mono-(2-hydroxy-3-methacryloyloxypropoxy)-propyl capped mono-n-butyl capped polydimethylsiloxanes (OH-mPDMS) having different molecular weights, such as mixtures of OH-mPDMS containing 4 and 15 SiO repeating units; mixtures of OH-mPDMS having different molecular weights (e.g., containing 4 and 15 repeating SiO repeating units) with silicone-based crosslinkers such as bis-3-acryloyloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS); mixtures of 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsilyloxy)silylpropoxy]-propyl methacrylate (SiMAA) and mono-methacryloyloxypropyl capped mono-n-butyl capped polydimethylsiloxane (mPDMS) such as mPDMS 1000.

[0177] The silicone-containing components for use in the present invention may have an average molecular weight of from about 400 daltons to about 4000 daltons.

[0178] Based on all the reactive components (excluding diluents) of the reactive mixture, one or more silicone-containing components may be present in an amount of up to about 95% by weight, or from about 10% to about 80% by weight, or from about 20% to about 70% by weight.

[0179] Polyamide

[0180] The reactive mixture may comprise at least one polyamide. As used herein, the term "polyamide" refers to polymers and copolymers comprising repeating units containing amide groups. Polyamides may include cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Acyclic polyamides contain acyclic amide side groups and are capable of binding to hydroxyl groups. Cyclic polyamides contain cyclic amide groups and are capable of binding to hydroxyl groups.

[0181] Examples of suitable acyclic polyamides include polymers and copolymers comprising repeating units of formulae G1 and G2:

[0182]

[0183] wherein X is a direct bond, -(CO)- or -(CONHR 44 )-, wherein R 44 is a C1 to C3 alkyl group; R 40 is selected from H, straight-chain or branched substituted or unsubstituted C1 to C4 alkyl groups; R 41Selected from H, linear or branched substituted or unsubstituted C1-C4 alkyl groups, amino groups having at most two carbon atoms, amide groups having at most four carbon atoms, and alkoxy groups having at most two carbon groups; R 42 Selected from H, linear or branched substituted or unsubstituted C1-C4 alkyl groups; or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 43 Selected from H, linear or branched substituted or unsubstituted C1-C4 alkyl groups; or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; wherein R 40 and R 41 The number of carbon atoms in together is 8 or less, including 7, 6, 5, 4, 3 or less; and wherein R 42 and R 43 The number of carbon atoms in together is 8 or less, including 7, 6, 5, 4, 3 or less. R 40 and R 41 The number of carbon atoms in together may be 6 or less or 4 or less. R 42 and R 43 The number of carbon atoms in together may be 6 or less. As used herein, substituted alkyl groups include alkyl groups substituted with amine, amide, ether, hydroxy, carbonyl, or carboxyl groups or combinations thereof.

[0184] R 40 and R 41 may be independently selected from H, substituted or unsubstituted C1-C2 alkyl groups. X may be a direct bond, and R 40 and R 41 may be independently selected from H, substituted or unsubstituted C1-C2 alkyl groups. R 42 and R 43 may be independently selected from H, substituted or unsubstituted C1-C2 alkyl groups, methyl, ethoxy, hydroxyethyl, and hydroxymethyl.

[0185] The acyclic polyamides of the present invention may comprise a majority of repeating units of formula LV or formula LVI, or the acyclic polyamides may comprise at least 50 mol% (including at least 70 mol% and at least 80 mol%) of repeating units of formula G or formula G1. Specific examples of the repeating units of formula G and formula G1 include repeating units derived from the following: N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropanamide, N-vinyl-N-methyl-2-methylpropanamide, N-vinyl-2-methyl-propanamide, N-vinyl-N,N'-dimethylurea, N,N-dimethylacrylamide, methacrylamide, and the acyclic amides of formula G2 and G3:

[0186]

[0187]

[0188] Examples of suitable cyclic amides that can be used to form cyclic polyamides include α-lactams, β-lactams, γ-lactams, δ-lactams, and ε-lactams. Examples of suitable cyclic polyamides include polymers and copolymers containing repeating units of formula G4:

[0189]

[0190] wherein R 45 is a hydrogen atom or a methyl group; wherein f is a number from 1 to 10; wherein X is a direct bond, -(CO)-, or -(CONHR 46 ), where R 46 is a C1 to C3 alkyl group. In formula LIX, f can be 8 or less, including 7, 6, 5, 4, 3, 2, or 1. In formula G4, f can be 6 or less, including 5, 4, 3, 2, or 1. In formula G4, f can be from 2 to 8, including 2, 3, 4, 5, 6, 7, or 8. In formula LIX, f can be 2 or 3. When X is a direct bond, f can be 2. In such cases, the cyclic polyamide can be polyvinylpyrrolidone (PVP).

[0191] The cyclic polyamides of the present invention can contain 50 mol% or more of repeating units of formula G4, or the cyclic polyamides can contain at least 50 mol% (including at least 70 mol% and at least 80 mol%) of repeating units of formula G4.

[0192] The polyamide may also be a copolymer comprising repeating units of both cyclic and acyclic amides. The additional repeating units may be formed from monomers selected from: hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, other hydrophilic monomers, and siloxane-substituted (meth)acrylates. Any of the monomers (listed as suitable hydrophilic monomers) may be used as a comonomer to form the additional repeating units. Specific examples of additional monomers that can be used to form the polyamide include 2-hydroxyethyl (meth)acrylate, vinyl acetate, acrylonitrile, hydroxypropyl (meth)acrylate, methyl (meth)acrylate and hydroxybutyl (meth)acrylate, dipropylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, etc., and mixtures thereof. It may also contain ionic monomers. Examples of ionic monomers include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL, CAS#148969-96-4), 3-acrylamidopropionic acid (ACA1), 5-acrylamidopropionic acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propanaminium inner salt (CBT, carboxybetaine; CAS 79704-35-1), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propanaminium inner salt (SBT, sulfobetaine, CAS 80293-60-3), 3,5-dioxa-8-aza-4-phosphaundec-10-ene-1-ammonium, 4-hydroxy-N,N,N-trimethyl-9-oxo-4-oxide inner salt (9CI) (PBT, phosphobetaine, CAS 163674-35-9), 2-methacryloyloxyethylphosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), (methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0193] The reactive monomer mixture can contain both acyclic polyamides and cyclic polyamides or their copolymers. The acyclic polyamides can be any of those acyclic polyamides described herein or their copolymers, and the cyclic polyamides can be any of those cyclic polyamides described herein or their copolymers. The polyamide can be selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and their copolymers and mixtures. The polyamide can be a mixture of PVP (e.g., PVP K90) and PVMA (e.g., having an M w )

[0194] In all cases, based on the total weight of the reactive components in the reactive monomer mixture, the total amount of all polyamides in the reactive mixture can be in the range of 1 wt% to about 35 wt%, including in the range of about 1 wt% to about 15 wt% and in the range of about 5 wt% to about 15 wt%.

[0195] Without wishing to be bound by theory, when used with a silicone hydrogel, the polyamide acts as an internal wetting agent. The polyamides of the present invention can be non-polymerizable and, in this case, are incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamide is trapped or physically retained within the silicone hydrogel. Alternatively, the polyamides of the present invention are polymerizable, for example, as polyamide macromonomers or prepolymers, and in this case are covalently introduced into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable polyamides can also be used.

[0196] When the polyamides are incorporated into the reactive monomer mixture, their weight-average molecular weight can be at least 100,000 daltons; greater than about 150,000; about 150,000 to about 2,000,000 daltons; about 300,000 daltons to about 1,800,000 daltons. Higher molecular weight polyamides can be used if they are compatible with the reactive monomer mixture.

[0197] Crosslinking Agent

[0198] It is generally desirable to add one or more crosslinking agents (also referred to as crosslinking monomers, polyfunctional macromonomers, and prepolymers) to the reactive mixture. The crosslinking agents can be selected from bifunctional crosslinking agents, trifunctional crosslinking agents, tetrafunctional crosslinking agents, and mixtures thereof, including silicone-containing and non-silicone-containing crosslinking agents. Non-silicone-containing crosslinking agents include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol trimethacrylate, 2-hydroxyethyl vinyl carbonate methacrylate (HEMAVc), allyl methacrylate, methylene bisacrylamide (MBA), and polyethylene glycol dimethacrylate (wherein the polyethylene glycol has a molecular weight of up to about 5000 daltons). The crosslinking agents are used in the reactive mixture in conventional amounts (e.g., from about 0.000415 moles to about 0.0156 moles per 100 grams of the reactive formulation). Alternatively, if the hydrophilic monomers and / or silicone-containing components are polyfunctional due to molecular design or due to impurities, the addition of the crosslinking agent to the reactive mixture is optional. Examples of hydrophilic monomers and macromonomers that can act as crosslinking agents and that (when present) obviate the need to add additional crosslinking agents to the reactive mixture include (meth)acrylate- and (meth)acrylamide-terminated polyethers. Other crosslinking agents will be known to those skilled in the art and can be used to prepare the silicone hydrogels of the present invention.

[0199] It may be desirable to select crosslinking agents that have similar reactivity to one or more of the other reactive components in the formulation. In some cases, it may be desirable to select a mixture of crosslinking agents having different reactivities to control some of the physical, mechanical, or biological properties of the resulting silicone hydrogel. The structure and morphology of the silicone hydrogel can also be affected by one or more diluents and curing conditions used.

[0200] Polyfunctional silicone-containing components (including macromonomers, crosslinking agents, and prepolymers) can also be included to further increase the modulus and maintain the tensile strength. The silicone-containing crosslinking agents can be used alone or in combination with other crosslinking agents. Examples of silicone-containing components that can act as crosslinking agents and that (when present) obviate the need to add crosslinking monomers to the reactive mixture include α,ω-bis(methacryloyloxypropyl)polydimethylsiloxane. Another example is bis-3-acryloyloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS).

[0201] Crosslinkers having a rigid chemical structure and polymerizable groups that undergo free radical polymerization can also be used. Non-limiting examples of suitable rigid structures include crosslinkers containing phenyl rings and benzyl rings, such as 1,4-phenylene diacrylate, 1,4-phenylene dimethacrylate, 2,2-bis(4-methacryloxyphenyl)-propane, 2,2-bis[4-(2-acryloxyethoxy)phenyl]propane, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane, and 4-vinylbenzyl methacrylate, and combinations thereof. Based on the total weight of all reactive components, the rigid crosslinker can be included in an amount between about 0.5 and about 15, or 2 to 10, 3 to 7. By adjusting the components in the reactive mixture, the physical and mechanical properties of the silicone hydrogel of the present invention can be optimized for specific uses.

[0202] Non-limiting examples of silicone crosslinkers also include the polyfunctional silicone-containing components described in Table D above.

[0203] Additional Component

[0204] The reactive mixture can contain additional components such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, drugs, nutritional agents, antimicrobial substances, toners, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, visible hues, and combinations thereof.

[0205] Classes of diluents suitable for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbon atoms, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. The diluent can be a primary alcohol, secondary alcohol, or tertiary alcohol.

[0206] Generally, reactive components are mixed in a diluent to form a reactive mixture. Suitable diluents are known in the art. Diluents suitable for silicone hydrogels are disclosed in WO 03 / 022321 and US6020445, the disclosures of which are incorporated herein by reference. Classes of diluents suitable for reactive mixtures of silicone hydrogels include alcohols having 2 to 20 carbons, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. Primary and tertiary alcohols can be used. Preferred classes include alcohols having 5 to 20 carbons and carboxylic acids having 10 to 20 carbon atoms. Specific diluents that can be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butyl alcohol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropoxy)propylbis(trimethylsilyloxy)methylsilane, 1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol, tert-butoxyethanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, 2-(diisopropylamino)ethanol, mixtures thereof, and the like. Examples of amide diluents include N,N-dimethylpropanamide and dimethylacetamide.

[0207] Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, tert-amyl alcohol, tert-butyl alcohol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, mixtures thereof, and the like.

[0208] More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, tert-pentanol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, mixtures thereof, and the like. If a diluent is present, there is generally no particular limitation on the amount of diluent present. When a diluent is used, based on the total weight of the reactive mixture (including reactive and non-reactive formulations), the diluent may be present in an amount in the range of from about 2 wt% to about 70 wt% (including in the range of from about 5 wt% to about 50 wt% and in the range of from about 15 wt% to about 40 wt%). Mixtures of diluents may be used.

[0209] Polymerization initiators can be used in the reactive mixture. The polymerization initiators can include, for example, at least one of lauroyl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, etc. that generate free radicals at a moderate high temperature; and photoinitiator systems such as aromatic α-hydroxy ketones, alkoxyoxobenzoins, acetophenones, acylphosphine oxides, diacylphosphine oxides, and tertiary amine plus diketones, mixtures thereof, and the like. Exemplary examples of photoinitiators are 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenylpropan-1-one, bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphine oxide (DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenyl phosphine oxide (Irgacure 819), 2,4,6-trimethylbenzyl diphenyl phosphine oxide, and 2,4,6-trimethylbenzoyl diphenyl phosphine oxide, benzoin methyl ester, and a composition of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.

[0210] Visible light initiator systems that are commercially available (from IGM Resins B.V., The Netherlands) include 819, 1700, 1800, 819, 1850, and TPO initiator. UV photoinitiators that are commercially available (from IGM Resins B.V.) include 1173, and 2959. These and other photoinitiators that can be used are disclosed in Volume III, Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, 2nd Edition, by J.V. Crivello & K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reactive mixture in an effective amount to initiate the photopolymerization of the reactive mixture (e.g., from about 0.1 parts by weight to about 2 parts by weight per 100 parts of the reactive monomer mixture). Depending on the polymerization initiator used, appropriately selected heat or visible light or ultraviolet light or other means can be used to initiate the polymerization of the reactive mixture. Alternatively, initiation can be carried out using an electron beam in the absence of a photoinitiator. However, when a photoinitiator is used, preferred initiators are diacylphosphine oxides such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide ( 819) or a combination of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide (DMBAPO).

[0211] The reactive mixture for manufacturing the ophthalmic device of the present invention, in addition to containing the compounds of the present invention, may also contain any of the above polymerizable compounds and optional components.

[0212] The reactive mixture may contain: compounds of the present invention, such as compounds of formula I and hydrophilic components.

[0213] The reactive mixture may contain: compounds of the present invention, such as compounds of formula I; and hydrophilic components selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof. Preferably, it is a mixture of HEMA and methacrylic acid.

[0214] The reactive mixture may contain: compounds of the present invention, such as compounds of formula I, hydrophilic components, and silicone-containing components.

[0215] The reactive mixture may comprise: a compound of the present invention, such as a compound of formula I; a hydrophilic component selected from DMA, HEMA, and mixtures thereof; a silicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsilyloxy)silylpropoxy]propyl methacrylate (SiMAA), mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS), mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated mono-n-butyl-terminated polydimethylsiloxane (OH-mPDMS), and mixtures thereof; and a wetting agent (preferably PVP or PVMA). For the hydrophilic component, a mixture of DMA and HEMA is preferred. For the silicone-containing component, a mixture of SiMAA and mPDMS is preferred.

[0216] The reactive mixture may comprise: a compound of the present invention, such as a compound of formula I; a hydrophilic component comprising a mixture of DMA and HEMA; a silicone-containing component comprising a mixture of OH-mPDMS having 2 to 20 repeating units (preferably a mixture of 4 and 15 repeating units). Preferably, the reactive mixture further comprises a silicone-containing crosslinker, such as ac-PDMS. Also preferably, the reactive mixture contains a wetting agent (preferably DMA, PVP, PVMA, or mixtures thereof).

[0217] The reactive mixture may comprise: a compound of the present invention, such as a compound of formula I; at least one polyamide between about 1 wt% and about 15 wt% (e.g., acyclic polyamide, cyclic polyamide, or mixtures thereof); at least one first monofunctional hydroxy-substituted poly(disubstituted siloxane) having 4 to 8 siloxane repeating units (e.g., OH-mPDMS, where n is 4 to 8, preferably n is 4); at least one second hydroxy-substituted poly(disubstituted siloxane) which is a monofunctional hydroxy-substituted poly(disubstituted siloxane) having 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20 siloxane repeating units (e.g., OH-mPDMS, where n is 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20, preferably n is 15); at least one hydrophilic monomer from about 5 wt% to about 35 wt%; and optionally a polyfunctional hydroxy-substituted poly(disubstituted siloxane) having 10 to 200 or 10 to 100 siloxane repeating units (e.g., ac-PDMS). Preferably, the first monofunctional hydroxy-substituted poly(disubstituted siloxane) and the second hydroxy-substituted poly(disubstituted siloxane) are present at a concentration such that the ratio of the weight percentage of the first monofunctional hydroxy-substituted poly(disubstituted siloxane) to the weight percentage of the second hydroxy-substituted poly(disubstituted siloxane) is 0.4 to 1.3 or 0.4 to 1.0.

[0218] The foregoing reactive mixture may contain optional components such as, but not limited to, one or more initiators, internal wetting agents, crosslinking agents, other UV or HEV absorbers, and diluents.

[0219] Curing of Hydrogel and Manufacture of Lenses

[0220] The reactive mixture can be formed by any one of the methods known in the art, such as shaking or agitation, and is used by known methods to form polymer articles or devices. The reactive components are mixed together with or without a diluent to form the reactive mixture.

[0221] For example, an ophthalmic device can be prepared by mixing the reactive components and optionally one or more diluents with a polymerization initiator and curing under appropriate conditions to form a product, which can then be shaped into an appropriate shape by turning, cutting, etc. Alternatively, the reactive mixture can be placed in a mold and subsequently cured into an appropriate article.

[0222] A method of manufacturing a molded ophthalmic device such as a silicone hydrogel contact lens may include: preparing a reactive monomer mixture; transferring the reactive monomer mixture onto a first mold; placing a second mold on top of the first mold filled with the reactive monomer mixture; and curing the reactive monomer mixture by free radical copolymerization to form a silicone hydrogel in the shape of a contact lens.

[0223] The reactive mixture can be cured via any known process for molding the reactive mixture during the production of contact lenses, including spin casting and static mold casting. Spin casting is disclosed in U.S. Patent Nos. 3,408,429 and 3,660,545, and the static mold casting method is disclosed in U.S. Patent Nos. 4,113,224 and 4,197,266. The contact lenses of the present invention can be formed by directly molding a silicone hydrogel, which is both economical and capable of precisely controlling the final shape of the hydrated lens. For this method, the reactive mixture is placed in a mold having the shape of the final desired silicone hydrogel, and the reactive mixture is subjected to conditions that polymerize the monomers, thereby producing a polymer having substantially the shape of the final desired product.

[0224] After curing, the lens can be extracted to remove unreacted components and release the lens from the lens mold. Extraction can be carried out using a conventional extraction liquid (such as an organic solvent like alcohol), or an aqueous solution extraction can be used.

[0225] An aqueous solution is a solution containing water. The aqueous solution of the present invention may contain at least about 20% by weight of water, or at least about 50% by weight of water, or at least about 70% by weight of water, or at least about 95% by weight of water. The aqueous solution may also contain additional water-soluble formulations, such as inorganic salts or release agents, wetting agents, lubricants, pharmaceutical and nutritional formulations, combinations thereof, and the like. A release agent is a compound or mixture of compounds that, when combined with water, shortens the time required to release a contact lens from a mold compared to using an aqueous solution without a release agent. The aqueous solution may not require special treatment, such as purification, recycling, or special disposal procedures.

[0226] Extraction can be achieved, for example, by immersing the lens in the aqueous solution or exposing it to a flowing aqueous solution. Extraction may also include, for example, one or more of the following: heating the aqueous solution; stirring the aqueous solution; increasing the content of the release aid in the aqueous solution to a level sufficient to release the lens; mechanically or ultrasonically agitating the lens; and incorporating at least one filtering or extraction aid into the aqueous solution until a level sufficient to promote the sufficient removal of unreacted components from the lens is reached. The above operations can be carried out in a batch or continuous process, with heating, stirring, or both, or without.

[0227] It may be desirable to apply physical agitation to facilitate leaching and demolding. For example, the lens mold part adhered with the lens can be vibrated or moved back and forth in the aqueous solution. Other methods may include ultrasound through the aqueous solution.

[0228] The lens can be sterilized by known means, including but not limited to autoclaving.

[0229] As described above, the preferred ophthalmic device is a contact lens, more preferably a soft hydrogel contact lens. The transmission wavelengths and percentages described herein can be measured for lenses of various thicknesses using, for example, the methods described in the examples. By way of example, the preferred central thickness for measuring the transmission spectrum in a soft contact lens can be 80 microns to 100 microns, or 90 microns to 100 microns, or 90 microns to 95 microns. Generally, the measurement can be carried out at the center of the lens using, for example, an instrument slit width of 4 nm.

[0230] The silicone hydrogel ophthalmic device (e.g., contact lens) according to the present invention preferably exhibits the following characteristics. All values are preceded by "about", and the device can have any combination of the listed characteristics. The characteristics can be determined by methods known to those skilled in the art, such as those described in U.S. pre-grant publication US20180037690, which is incorporated herein by reference.

[0231] Water concentration %: at least 20% or at least 25% and at most 80% or at most 70%

[0232] Haze: 30% or less, or 10% or less

[0233] Advancing dynamic contact angle (Wilhelmy plate method): 100° or less, or 80° or less, or 50° or less

[0234] Tensile modulus (psi): 120 or less, or 80 to 120

[0235] Oxygen permeability (Dk, Barrere): at least 80, or at least 100, or at least 150, or at least 200

[0236] Elongation at break: at least 100

[0237] For ionosilicon hydrogels, the following properties may also be preferred (in addition to those above):

[0238] Lysozyme absorption rate (μg / lens): at least 100, or at least 150, or at least 500, or at least 700

[0239] Polyquaternium-1 (PQ1) uptake (%): 15 or less, or 10 or less, or 5 or less

[0240] In addition to ophthalmic devices, the compounds of the present invention can also be used with other products. For example, the compounds can be used in windows (e.g., vehicle or building windows) or optical devices such as binoculars and cameras. In such uses, the compounds can be coated on the surface of the device, for example. To facilitate coating, the compounds can be dissolved in a solvent.

[0241] The following clauses list non-limiting embodiments of the present disclosure:

[0242] 1. A compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 100 nm at the maximum visible light absorption, wherein the compound is photo-stable (e.g., when measured according to ICH guideline Q1B).

[0243] 2. The compound according to clause 1, wherein the maximum visible light absorption is between 440 nm and 470 nm.

[0244] 3. The compound according to any one of clauses 1 to 2, wherein the FWHM at the maximum visible light absorption is at least 40 nm and at most 95 nm.

[0245] 4. The compound according to any one of clauses 1 to 3, wherein the photo-stability comprises an absorbance loss of no more than 20% at the maximum visible light absorption.

[0246] 5. A compound having a maximum visible light absorption between 430 nm and 480 nm and a maximum full width at half maximum (FWHM) of at least 35 nm and at most 100 nm at the maximum visible light absorption, wherein the compound is more photostable than macular pigment (e.g., when measured according to ICH guideline Q1B).

[0247] 6. A compound according to any one of clauses 1 to 5, the compound comprising a chromophore having a substructure of formula I:

[0248]

[0249] wherein EWG is an electron-withdrawing group.

[0250] 7. A compound according to clause 6, wherein EWG is cyano, amide, ester, keto or aldehyde.

[0251] 8. A compound according to any one of clauses 6 to 7, wherein EWG is cyano.

[0252] 9. A compound according to clause 6, the compound having formula II:

[0253]

[0254] wherein m and n are independently 0, 1, 2, 3 or 4; T is a bond, O or NR 6 , wherein R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or Y-P g ; R is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Y is a linking group; P g is a polymerizable group; when R 1 and R 2 are present, each occurrence thereof is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation such as sodium or potassium), wherein R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2 groups, the two adjacent groups combining with the carbon atom to which they are attached to form a cycloalkyl or aryl ring; and EWG is an electron-withdrawing group.

[0255] 10. The compound according to clause 6, wherein the compound is: ethyl (E)-2-(2-cyano-2-(2-methoxy-10-propylacridin-9(10H)-ylidene)acetamido)methacrylate; or ethyl (E)-2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)methacrylate.

[0256] 11. The compound according to any one of clauses 1 to 10, wherein the photostability comprises an absorbance loss of no more than 20% at the maximum visible light absorption.

[0257] 12. The compound according to any one of clauses 1 to 11, wherein the compound has a molar extinction coefficient of at least 7740.

[0258] 13. An ophthalmic device, comprising the compound according to any one of clauses 1 to 12.

[0259] 14. A contact lens or an intraocular lens, which is a polymerization product of a reactive mixture comprising: (a) a monomer suitable for manufacturing the ophthalmic device; and (b) the compound according to any one of clauses 1 to 12.

[0260] 15. A spectacle lens or a sunglass lens, comprising: (a) a mineral material or an organic material or a combination thereof, and (b) the compound according to any one of clauses 1 to 12.

[0261] 16. The compound, ophthalmic device or spectacle lens according to any one of clauses 1 to 15, which is imported into a certain country.

[0262] 17. The compound, ophthalmic device or spectacle lens according to clause 16, wherein the country is the United States.

[0263] 18. A compound having a maximum visible light absorption between 430 nm and 480 nm and a maximum full width at half maximum (FWHM) of at least 35 nm and at most 100 nm at the maximum visible light absorption, wherein the compound is photostable (e.g., when measured according to ICH guideline Q1B), and wherein the compound has a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 -1.

[0264] 19. The compound according to clause 18, wherein the maximum visible light absorption is between 440 nm and 470 nm.

[0265] 20. A compound according to any one of clauses 18 to 19, wherein the FWHM at the visible light absorption maximum is at least 40 nm and at most 95 nm.

[0266] 21. A compound according to any one of clauses 18 to 20, wherein the photo-stability comprises an absorbance loss of no more than 20% at the visible light absorption maximum.

[0267] 22. A compound having a visible light absorption maximum between 430 nm and 480 nm and a full width at half maximum (FWHM) at the visible light absorption maximum of at least 35 nm and at most 100 nm, wherein the compound is more photo-stable than macular pigment (e.g., when measured according to ICH guideline Q1B), and wherein the compound has a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 of the molar extinction coefficient.

[0268] 23. A compound comprising a chromophore having a sub-structure of formula I:

[0269]

[0270] wherein EWG is an electron-withdrawing group, and the compound has a visible light absorption maximum in the range of 440 nm to 480 nm.

[0271] 24. A compound according to clause 23, wherein EWG is cyano, amide, ester, keto or aldehyde.

[0272] 25. A compound according to any one of clauses 23 to 24, wherein EWG is cyano.

[0273] 26. A compound according to clause 23, the compound having formula II:

[0274]

[0275] wherein m and n are independently 0, 1, 2, 3 or 4; T is a bond, O or NR 6 , wherein R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or Y-P g ; R is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Y is a linking group; P g is a polymerizable group; when R 1 and R 2, which is independently, upon each occurrence, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 thioalkyl group, a C3-C7 cycloalkyl group, an aryl group (preferably unsubstituted phenyl or phenyl substituted by an alkyl or halo group), a halo group, a hydroxyl group, an amino group, NR 3 R 4 , a benzyl group, SO3H or SO3M (where M is a monovalent cation such as sodium or potassium), wherein R 3 and R 4 are independently H or a C1-C6 alkyl group, or two adjacent R 1 or R 2 groups, and the two adjacent groups combine with the carbon atom to which they are attached to form a cycloalkyl or aryl ring; and EWG is an electron-withdrawing group.

[0276] 27. The compound according to clause 23, wherein the compound is:

[0277] (E)-2-(2-cyano-2-(2-methoxy-10-propylacridin-9(10H)-ylidene)acetamido)ethyl methacrylate; or

[0278] (E)-2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)ethyl methacrylate.

[0279] 28. The compound according to any one of clauses 23 to 27, wherein the compound has a full width at half maximum (FWHM) of at least 35 nm and at most 100 nm at the visible light absorption maximum, and wherein the compound is photostable (e.g., when measured according to ICH guideline Q1B).

[0280] 29. The compound according to clause 28, wherein the visible light absorption maximum is between 440 nm and 470 nm.

[0281] 30. The compound according to any one of clauses 28 to 29, wherein the FWHM at the visible light absorption maximum is at least 40 nm and at most 95 nm.

[0282] 31. The compound according to any one of clauses 28 to 30, wherein the photostability comprises an absorbance loss of no more than 20% at the visible light absorption maximum.

[0283] 32. The compound according to any one of clauses 23 to 31, wherein the compound has a full width at half maximum (FWHM) of at least 35 nm and at most 100 nm at the visible light absorption maximum, and wherein the compound is more photostable than macular pigment (e.g., when measured according to ICH guideline Q1B).

[0284] 33. A compound according to any one of clauses 23 to 32, said compound having a molar extinction coefficient of at least 7740 L.mol - 1 .cm -1 .

[0285] 34. An ophthalmic device, said ophthalmic device comprising a compound according to any one of clauses 18 to 33.

[0286] 35. A contact lens or an intraocular lens, said contact lens or intraocular lens being a polymerization reaction product of a reactive mixture comprising: (a) monomers suitable for manufacturing said ophthalmic device; and (b) a compound according to any one of clauses 18 to 33.

[0287] 36. An eyeglass lens or a sunglass lens, said eyeglass lens or sunglass lens comprising: (a) a mineral material or an organic material or a combination thereof, and (b) a compound according to any one of clauses 18 to 33.

[0288] 37. A compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) at said maximum visible light absorption of at least 35 nm and at most 150 nm, preferably at most 100 nm, wherein said compound is thermally stable.

[0289] 38. A compound according to clause 37, wherein said compound has a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 .

[0290] 39. A compound according to clause 37, wherein said maximum visible light absorption is between 440 nm and 470 nm.

[0291] 40. A compound according to any one of clauses 37 to 39, wherein the FWHM at said maximum visible light absorption is at least 40 nm and at most 95 nm.

[0292] 41. A compound according to any one of clauses 37 to 40, wherein the thermal stability comprises an absorbance loss of not more than 20% at said maximum visible light absorption.

[0293] 42. A compound having a maximum visible light absorption between 430 nm and 480 nm and a maximum full width at half maximum (FWHM) of at least 35 nm and at most 150 nm, preferably at most 100 nm, at the maximum visible light absorption, wherein the compound is more thermally stable than macular pigment, and wherein the compound optionally has a molar extinction coefficient of at least 7740 L.mol -1 .cm -1 .

[0294] 43. A compound comprising a chromophore having a substructure of formula I:

[0295]

[0296] wherein EWG is an electron-withdrawing group and the compound has a maximum visible light absorption in the range of 440 nm to 480 nm.

[0297] 44. The compound according to clause 43, wherein EWG is cyano, amide, ester, keto or aldehyde.

[0298] 45. The compound according to any one of clauses 43 to 44, wherein EWG is cyano.

[0299] 46. The compound according to clause 43, the compound having formula II:

[0300]

[0301] wherein m and n are independently 0, 1, 2, 3 or 4; T is a bond, O or NR 6 , where R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or Y-P g ; R is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Y is a linking group; P g is a polymerizable group; when R 1 and R 2 are present, each occurrence thereof is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation such as sodium or potassium), where R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2a group, wherein the two adjacent groups together with the carbon atom to which they are attached combine to form a cycloalkyl or aryl ring; and EWG is an electron-withdrawing group.

[0302] 47. The compound according to clause 43, wherein the compound is:

[0303] (E)-ethyl 2-(2-cyano-2-(2-methoxy-10-propylacridin-9(10H)-ylidene)acetamido)methacrylate; or

[0304] (E)-ethyl 2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)methacrylate.

[0305] 48. The compound according to any one of clauses 43 to 47, wherein the compound has a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm, preferably at most 100 nm, at the visible light absorption maximum, and wherein the compound is thermally stable.

[0306] 49. The compound according to clause 48, wherein the visible light absorption maximum is between 440 nm and 470 nm.

[0307] 50. The compound according to any one of clauses 48 to 49, wherein the FWHM at the visible light absorption maximum is at least 40 nm and at most 95 nm.

[0308] 51. The compound according to any one of clauses 48 to 50, wherein the thermal stability comprises an absorbance loss of not more than 20% at the visible light absorption maximum.

[0309] 52. The compound according to any one of clauses 43 to 51, wherein the compound has a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm, preferably at most 100 nm, at the visible light absorption maximum, and wherein the compound is more thermally stable than macular pigment.

[0310] 53. The compound according to any one of clauses 43 to 52, wherein the compound has a molar extinction coefficient of at least 7740 L.mol - 1 .cm -1 of the molar extinction coefficient.

[0311] 54. An ophthalmic device, the ophthalmic device comprising a compound according to any one of clauses 37 to 53.

[0312] 55. A contact lens or an intraocular lens, which is a polymerization product of a reactive mixture comprising: (a) monomers suitable for manufacturing the ophthalmic device; and (b) a compound according to any one of clauses 37 to 53.

[0313] 56. An ophthalmic lens or a sunglass lens, which comprises: (a) a mineral material, an organic material, or a combination thereof, and (b) a compound according to any one of clauses 37 to 53.

[0314] 57. A method for preparing a compound of formula II:

[0315]

[0316] wherein m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR 6 , wherein R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or Y-P g ; R is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Y is a linking group; P g is a polymerizable group; when R 1 and R 2 are present, each occurrence of which is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , benzyl, SO3H, or SO3M (M is a monovalent cation such as sodium or potassium), wherein R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2 groups, the two adjacent groups combine with the carbon atom to which they are attached to form a cycloalkyl or aryl ring; and EWG is an electron-withdrawing group, the method comprising:

[0317] providing an N-substituted acridone of formula II-A:

[0318]

[0319] treating the N-substituted acridone with triphenylphosphine dibromide and a reagent of the following formula: and

[0320] isolating the compound of formula II.

[0321] 58. The method according to clause 57, wherein EWG is CN.

[0322] 59. The method according to any one of clauses 57 to 58, wherein m and n are 0.

[0323] 60. The method according to any one of clauses 57 to 59, wherein R is C1-C6 alkyl.

[0324] 61. A method according to any one of clauses 57 to 60, wherein T is NR 6 .

[0325] 62. The method according to clause 57, wherein the compound of formula II is:

[0326] or

[0327]

[0328] Some embodiments of the present invention will now be described in detail in the following examples.

[0329] Examples

[0330] Test Methods

[0331] The UV-visible spectra of the compounds in solution were measured on a Perkin Elmer Lambda 45, Agilent Cary 6000i, or Ocean Optics QE65 PRO (DH-2000-BAL light source) UV-VIS scanning spectrometer. The instrument was thermally equilibrated for at least thirty minutes before use. For the Perkin Elmer instrument, the scan range was 200nm to 800nm; the scan speed was 960nm / min; the slit width was 4nm; the mode was set to transmittance or absorbance; and baseline correction was selected. For the Cary instrument, the scan range was 200nm to 800nm; the scan speed was 600nm / min; the slit width was 2nm; the mode was transmittance or absorbance; and baseline correction was selected. For the Ocean Optics instrument, the scan range was 200nm-800nm; the slit width was 10μm; the mode was transmittance or absorbance; and baseline correction was selected. Baseline correction was performed before analyzing the sample using the autozero function.

[0332] Using a wetting solution, the ultraviolet-visible spectrum of a contact lens partially formed from the claimed composition was measured on a Perkin Elmer Lambda 45 UV / VIS, an Agilent Cary 6000i, or an OceanOptics UV-VIS scanning spectrometer. Prior to use, the instrument was thermally equilibrated for at least thirty minutes. Baseline correction was performed using a cuvette comprising a plastic two-piece lens holder and the same solvent. These two-piece contact lens holders were designed to hold the sample in the quartz cuvette in the position where the incident beam passes through. The reference cuvette also comprised a two-piece holder. To ensure a constant thickness of the sample, all lenses were made using the same mold. The central thickness of the contact lens was measured using an electronic thickness gauge. The reported central thickness and percentage transmission spectrum were obtained by averaging the data for three individual lenses.

[0333] It is important to ensure that the outer surface of the cuvette is completely clean and dry and that there are no air bubbles in the cuvette. The reproducibility of the measurement can be improved when the reference cuvette and its lens holder remain unchanged and when all samples are measured using the same sample cuvette and its lens holder, thereby ensuring correct insertion of the two cuvettes into the instrument.

[0334] The water content was determined gravimetrically. The lenses were equilibrated in the wetting solution for 24 hours. Each of the three test lenses was removed from the wetting solution with a cotton swab and placed on a blotting paper moistened with the wetting solution. Both sides of the lens were in contact with the blotting paper. The test lens was placed in the weighing pan of a balance with forceps and weighed. Two additional samples were prepared and weighed. All weight measurements were performed in triplicate and the average of those values was used for the calculation. The wet weight was defined as the total weight of the pan and the wet lens minus the weight of the pan weighed separately.

[0335] The dry weight was measured by placing the sample pan in a vacuum oven preheated to 60 °C for 30 minutes. A vacuum was applied until the pressure reached at least 1 inch of mercury (Hg); a lower pressure was allowed. The vacuum valve and pump were closed and the lens was dried for at least 12 hours, usually overnight. The bleed valve was opened to allow dry air or dry nitrogen to enter. The oven was brought to atmospheric pressure. The pan was removed and weighed. The dry weight was defined as the total weight of the pan and the dry lens minus the weight of the pan weighed separately. The water content of the test lens was calculated as follows: water content % = (wet weight - dry weight) / wet weight × 100. The average value and standard deviation of the water content were calculated and the average value was reported as the water content % of the test lens.

[0336] The mechanical properties of the contact lenses are measured using a tensile testing machine, such as an Instron model 1122 or 5542 equipped with a load cell and pneumatic grip control. Lenses of -1 diopter are preferred lens geometries due to their uniform thickness distribution at the center. Dogbone-shaped specimens cut from -1 diopter spherical lenses having a length of 0.522 inches, an "ear" width of 0.276 inches, and a "neck" width of 0.213 inches are loaded into the fixture and stretched at a constant strain rate of 2 inches per minute until they break. Prior to testing, the center thickness of the dogbone specimens is measured using an electronic thickness gauge. The initial gauge length (L o ) and the length at break (L f ) of the specimens are measured. At least five specimens of each composition are measured, and the percent elongation at break is calculated using the average value: Percent elongation = [(L f - L o ) / L o × 100. The tensile modulus is calculated as the slope of the initial linear portion of the stress-strain curve; the modulus is in pounds per square inch or psi. The tensile strength is calculated from the peak load and the initial cross-sectional area: Tensile strength = peak load divided by the initial cross-sectional area; the unit of tensile strength is psi. The toughness is calculated from the fracture energy and the volume of the initial sample: Toughness = fracture energy divided by the initial sample volume; the unit of toughness is in-lbs / in 3 .

[0337] Contact lens parameters in a wetting solution are measured using calibrated dual interferometry. These parameters include the equivalent spherical power (diopters or D) at multiple apertures, the cylindrical power (diopters or D) at multiple apertures, the diameter (millimeters or mm), the center thickness (millimeters or mm), the sagittal height (millimeters or mm), and the root mean square (RMS) optical path wavefront deviation from the lens design target (in micrometers (micrometer or micron) (μm)), where the spherical power / cylindrical power and coma are removed as measured using a 6.5 mm aperture. The instrument consists of a custom-built propionic acid interferometer for measuring wavefront parameters and a Lumetrics II low coherence interferometer for measuring the dimensional parameters of the sagittal height and center thickness. The combination of the two separate instruments is similar to the Lumetrics Clearwave TM Plus, and the software is similar to the Lumetrics OptiGauge Control Center v7.0 or higher. Using Clearwave TMPlus, the camera is used to find the lens edge and then calculate the lens center, which is then used to align the 1310-nm interferometer probe at the lens center for measuring sagittal height and center thickness. A wavefront sensor (shack-Hartmann sensor) is also used in series to collect the transmitted wavefront. Multiple parameters of the transmitted wavefront from the contact lens are measured, and other parameters are calculated from those measurements.

[0338] Based on the collected data, difference terms are calculated by comparing the measured values with the targets. These include the root mean square optical path wavefront deviation from the lens design target in μm as measured using a 6.5-mm aperture (spherical / cylindrical power and coma removed) (RMS_65), the second equivalent spherical power deviation from the lens design target in diopters (D) as measured using a 5-mm aperture (PW2EQD), the deviation from the lens design target diameter in mm (DMD), the deviation from the lens design target base curve radius in mm (BCD) calculated from the sagittal height and target lens diameter as measured according to ISO 18369-3, and the deviation from the lens design target center thickness in mm (CTD).

[0339] The following abbreviations will be used throughout the examples and figures and have the following meanings:

[0340] L: liter

[0341] mL: milliliter

[0342] Equiv. or eq.: equivalent

[0343] kg: kilogram

[0344] g: gram

[0345] mg: milligram

[0346] mol: mole

[0347] mmol: millimole

[0348] M: molar

[0349] Da: Dalton or g / mol

[0350] kDa: kilodalton or atomic mass unit equal to 1,000 daltons

[0351] min: minute

[0352] mm: millimeter

[0353] cm: centimeter

[0354] μm: micrometer

[0355] nm: nanometer

[0356] λ: wavelength

[0357] wt.%: weight percent

[0358] Cmpd: compound

[0359] TLC: thin layer chromatography

[0360] 1 H NMR: proton nuclear magnetic resonance spectroscopy

[0361] UV-VIS: ultraviolet-visible spectroscopy

[0362] AU: absorbance unit

[0363] BC: base-curved plastic mold

[0364] FC: front-curved plastic mold

[0365] PP: polypropylene, i.e., homopolymer of propylene

[0366] TT: Tuftec, i.e., hydrogenated styrene-butadiene block copolymer (Asahi Kasei Chemicals)

[0367] Z: Zeonor, i.e., polycycloolefin thermoplastic polymer (Nippon Zeon Co Ltd)

[0368] DMA: N,N-dimethylacrylamide (Jarchem)

[0369] HEMA: 2-hydroxyethyl methacrylate (Bimax)

[0370] PVP K90: poly(N-vinylpyrrolidone) (ISP Ashland)

[0371] TEGDMA: tetraethylene glycol dimethacrylate (Esstech)

[0372] Omnirad 1870: blend of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide and 1-hydroxycyclohexyl phenyl ketone (IGM Resins or BASF or Ciba Specialty Chemicals)

[0373] mPDMS: monomethacryloxypropyl-terminated poly(dimethylsiloxane) with a single n-butyl endcap (M n = 800 Dalton - 1500 Dalton) (Gelest)

[0374] SiMAA: 2 - Acrylic acid, 2 - methyl - 2 - hydroxy - 3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester (Toray) or 3 - (3 - (1,1,1,3,5,5,5 - heptamethyltrisiloxan - 3 - yl)propoxy)-2 - hydroxypropyl methacrylate

[0375] Norbloc: 2 - (2′ - hydroxy - 5 - methacryloyloxyethylphenyl)-2H - benzotriazole (Janssen)

[0376] LED: Light - emitting diode

[0377] D3O: 3,7 - dimethyloctan - 3 - ol (Vigon)

[0378] DIW: Deionized water

[0379] IPA: Isopropyl alcohol

[0380] CDCl3: Deuterochloroform

[0381] HCl: Hydrochloric acid

[0382] Borate - buffered wetting solution: Dissolve 18.52 g (300 mmol) of boric acid, 3.7 g (9.7 mmol) of sodium borate decahydrate, and 28 g (197 mmol) of sodium sulfate in sufficient deionized water to fill a 2 - liter volumetric flask.

[0383] Example 1: Synthesis of Ethyl (E)-2-(2-cyano-2-(2-methoxy-10-propylacridin-9(10H)-ylidene)acetamido)methacrylate (Compound A) as Shown in Scheme 1 Example 2: Synthesis of Ethyl (E)-2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)methacrylate (Compound B) as Shown in Scheme 2

[0384]

[0385] Charge 2 - iodobenzoic acid (12.40 g, ca. 0.05 mol), 12.32 g of 4 - methoxyaniline (ca. 2 equivalents), 6.91 g of anhydrous potassium carbonate (ca. 0.05 mol), and 300 mg of copper powder (4.76 mmol) into a 100 - mL three - necked round - bottom flask equipped with a magnetic stir bar and a reflux condenser. Add deionized water (30 mL) to the solid mixture and heat the system under reflux with continuous stirring for 6 h. The mixture solidifies upon cooling to room temperature. Dilute the system with deionized water and gradually pour it into 1 - equivalent aqueous hydrochloric acid solution with stirring. Stir the mixture at room temperature for 30 min, then filter it on a sintered - glass funnel and dry it in a vacuum oven at 60 °C. Wash the residue 2 - ((4 - methoxyphenyl)amino)benzoic acid with 3×100 mL of deionized water and use it "as is" for intramolecular cyclization. 11H NMR (CDCl3) - δ 3.81 (3H, s), 6.66 (1H, t), 6.89 - 6.93 (3H, m), 7.16 (2H, d), 7.27 (1H, t), 7.99 (1H, d), 9.12 (1H, bs).

[0386] 12.5 g of 2 - ((4 - methoxyphenyl)amino)benzoic acid and 100 mL of Eaton's acid (methanesulfonic acid solution with 10 wt% P2O5) were charged into a 250 mL round - bottom flask equipped with a magnetic stir bar and a reflux condenser. The mixture was heated at 90 °C (hood temperature) for 5 h with continuous stirring while monitoring the progress by TLC. After cooling to room temperature, the reaction mixture was poured onto ice, stirred for 30 min, and filtered on a sintered glass funnel. The residue, 2 - methoxyacridin - 9(10H) - one, was washed with 3 × 100 mL of deionized water, then with acetonitrile, and dried in a vacuum oven at 60 °C. 1 1H NMR (DMSO d6) - δ 3.86 (3H, s), 7.23 (1H, t), 7.41 (1H, dd), 7.52 (1H, d), 7.53 (1H, d), 7.63 (1H, d), 7.70 (1H, dt), 8.23 (1H, d).

[0387] 5.4 g of 2 - methoxyacridin - 9(10H) - one (0.0244 mol) and 12.9 g of cesium carbonate (about 1.5 equiv) were charged into a 250 mL round - bottom flask equipped with a magnetic stir bar and a reflux condenser. The solid was dried under vacuum at 80 °C, after which the system was placed under a nitrogen blanket and 80 mL of anhydrous N,N - dimethylformamide was added to the flask. 1 - Bromopropane (6.0 g, about 2 equiv) was added to the flask, and the mixture was heated at 50 °C (hood temperature) for 36 h. TLC indicated the presence of two compounds (O - alkylated and N - alkylated). The organic matter was poured into 200 mL of deionized water and extracted into about 150 mL of ethyl acetate. Then the organic matter was washed with 3 × 100 mL of water, followed by 3 × 100 mL of dilute HCl aqueous solution to remove the O - alkylated acridine by - product, and finally with deionized water. TLC of the organic matter indicated the presence of a single compound at this time, namely 2 - methoxy - 10 - propylacridin - 9(10H) - one, which was dried under reduced pressure and used for subsequent transformation. 1 1H NMR (CDCl3) - δ 1.12 (3H, t), 1.93 (2H, m), 4.28 (2H, dd), 7.25 (1H, ddd), 7.35 (1H, dd), 7.45 (1H, dd), 7.66 (1H, m), 7.96 (1H, d), 7.57 (1H, dd).

[0388] Charge a 250 mL three-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser with 4.5 g of 2-methoxy-10-propylacridin-9(10H)-one (0.017 mol) and 6.4 g of N-2-methacryloyloxyethyl-2-cyanoacetamide (0.033 mol). Place the system under a nitrogen blanket and add 20 mL of dichloromethane to the mixture and stir until homogeneous. After cooling the system in an ice bath, add titanium tetrachloride (4.5 mL, 7.78 g, 0.041 mol) dropwise to the mixture and continue stirring for an additional 15 minutes. Add 5 mL of pyridine (4.9 g, 0.06 mol) to the mixture, allow it to warm to ambient temperature, and then heat to reflux for 8 hours. After cooling the mixture to room temperature, pour it onto dilute aqueous HCl and extract the product mixture into dichloromethane. Evaporate the volatiles under reduced pressure and purify the product compound A by flash chromatography. 1 H NMR (CDCl3) - δ 1.07 (3H, t), 1.87 (3H, s), 1.91 (2H, m), 3.58 (2H, dd), 3.85 (3H, s), 4.07 (2H, dd), 4.18 (2H, t), 5.5 (1H, dd), 6.03 (1H, ss), 6.07 (1H, t), 7.07 (1H, t), 7.14 (1H, dd), 7.23 (2H, two doublets), 7.48 (1H, m), 7.92 (1H, bs).

[0389] An alternative synthesis of Compound B is shown in Scheme 3 Table 1

[0390]

[0391] Into a 200 mL round bottom flask equipped with a magnetic stir bar and a reflux condenser, 10.0 g of 2-methoxyacridine-9(10H)-one (0.044 mol) and 19.6 g of cesium carbonate (ca. 1.25 equiv) were charged. The solids were dried under vacuum at 80 °C, after which the system was placed under a nitrogen blanket and 60 mL of anhydrous DMSO was added to the flask. 1-Bromobutane (7.55 g, ca. 1.25 equiv) was added to the flask and the mixture was heated at 110 °C (mantle temperature) for 6 h. Two products were observed by TLC, with very close retention factors for the two products and inseparable by chromatography. The cooled suspension was poured onto 500 mL of deionized water and the mixture was stirred at room temperature for 30 min. The organics were extracted into ethyl acetate and washed with 3 × 200 mL of deionized water. NMR of the organics indicated the presence of an O-alkylated acridine derivative in addition to the desired compound 2-methoxy-10-butylacridine-9(10H)-one. This material could be used "as is" for the Knoevenagel condensation. Preferably, the crude product was washed with dilute aqueous HCl to remove the O-alkylated acridine derivative, affording pure 2-methoxy-10-butylacridine-9(10H)-one. 1 HNMR(CDCl3)-δ 1.05(3H, t), 1.55(2H, m), 1.82(2H, m), 4.31(2H, dd), 7.25(1H, ddd), 7.34(1H, dd), 7.45(1H, dd), 7.68(1H, m), 7.96(1H, d), 8.56(1H, dd).

[0392] Into a 250 mL three-neck round bottom flask equipped with a magnetic stir bar and a reflux condenser, 10.0 g of a crude product mixture containing 2-methoxy-10-butylacridine-9(10H)-one and 15 g of N-2-methacryloyloxyethyl-2-cyanoacetamide were charged. The system was placed under a nitrogen blanket, 150 mL of dichloromethane was added to the mixture and stirred until homogeneous. After cooling the system in an ice bath, titanium tetrachloride (10 mL, 17.3 g, 1.092 mol) was added dropwise to the mixture and stirring was continued for an additional 15 min. 10 mL of pyridine (9.82 g, 0.12 mol) was added to the mixture, which was then warmed to ambient temperature and then heated to reflux for 8 h. TLC indicated the presence of several compounds, including the unreacted O-alkylated derivative present in the starting material mixture. The major product - Compound B was a dark brownish orange species of slightly higher polarity, which was isolated after quenching the system in dilute aqueous HCl, followed by aqueous extraction and chromatographic analysis. 11H NMR (CDCl3) - δ 1.04 (3H, t), 1.51 (2H, m), 1.87 (3H, s, 2H, m), 3.58 (2H, dd), 3.84 (3H, s), 4.12 (2H, dd), 4.19 (2H, t), 5.55 (1H, dd), 6.03 (1H, bs), 6.07 (1H, t), 7.07 (1H, t), 7.15 (1H, dd), 7.25 (2H, two doublets), 7.48 (1H, t), 7.75 (1H, bs), 7.92 (1H, bs).

[0393] Figure 1

[0394]

[0395] When R is a n-butyl group, the synthesis of ethyl (E)-2-(2-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-2-cyanoacetamido)methacrylate or Compound B: Charge 9.43 g of triphenylphosphine (36 mmol) and 120 mL of anhydrous dichloromethane into a 3-necked 500 mL RBF equipped with a magnetic stir bar and a reflux condenser. Add bromine (5.76 g, 33 mmol) dropwise to this solution, stir it at room temperature for another 30 minutes, then add 10-butyl-2-methoxyacridin-9(10H)-one (8.43 g, 30 mmol) to this mixture and heat it to reflux for 18 hours. Add ethyl 2-(2-cyanoacetamido)methacrylate (8.23 g, 36 mmol, 1.4 equivalents) to this reaction mixture, heat this reaction mixture and stir it for another 8 hours. At this time, very little starting material was observed by TLC, and an orange-brown compound was observed at the baseline. Cool the mixture to room temperature, add 150 mL of aqueous sodium carbonate solution (about 10.6 g, 100 mmol of dissolved Na2CO3), and stir the mixture for 30 minutes. Treat with base to obtain the desired compound. Extract the aqueous layer with additional dichloromethane. Remove the organic matter under reduced pressure and purify the product by chromatography. First, rinse the raw material through silica gel with dichloromethane and ethyl acetate to remove polar components. Then, perform a second pass with ethyl acetate / hexane or ether / hexane after loading the material with the minimum amount of dichloromethane to obtain the desired product with a yield > 80%.

[0396] The selected absorption characteristics of Compound A and Compound B are shown in Table 1.

[0397] Example 3: Contact Lenses

[0398]

[0399] 1Full width at half maximum (FWHM) at λ maximum

[0400] In Table 2 The UV-VIS absorption spectra of 0.1 mM methanol solutions of Compound A and Compound B are shown and superimposed on the literature spectrum of macular pigment.

[0401] Figure 2

[0402] Prepare a reactive monomer mixture consisting of 77 wt% of the formulation listed in Table 2 and 23 wt% of diluent D3O. Filter the reactive monomer mixture under pressure through a 3 μm filter using a stainless steel syringe.

[0403] Example 4: Thermal and Photochemical Stability Tests

[0404]

[0405] Degas the reactive monomer mixture at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than about 0.1% to 0.2% oxygen, dispense approximately 75 μL of the reactive mixture into an FC made of a 90:10 (weight / weight) Z / TT blend at room temperature using an Eppendorf pipette. Then place a BC made of a 90:10 (w / w) Z:TT blend on the FC. Before dispensing, allow the mold to equilibrate in the glove box for at least twelve hours. Transfer a tray containing eight mold assemblies each to an adjacent glove box maintained at 62 °C and cure the lenses from the top and bottom for 10 minutes using a 405 nm LED lamp with an intensity of approximately 2.0 mW / cm2.

[0406] Manually demold the lenses and detach the lenses by suspending the lenses in approximately one liter of 70% IPA for approximately one hour, then soaking twice more in fresh 70% IPA for 30 minutes; then overnight in DIW; subsequently treating with fresh DIW for 30 minutes; and then soaking in a wetting solution for 30 minutes. Finally, equilibrate and store the lenses in a borate buffered wetting solution. One of ordinary skill in the art recognizes that the exact lens detachment process can vary depending on the lens formulation and molding material in terms of the concentration of the aqueous isopropanol solution, the number of washes with each solvent, and the duration of each step. The purpose of the lens detachment process is to detach all lenses without defects and transform from a diluent-swollen network to a wetting solution-swollen hydrogel.

[0407] In Table 3 The UV-VIS transmission spectra of two different sets of lenses (Example 3A and Example 3B) in a borate buffered wetting solution are shown.

[0408] Figure 3

[0409] Prepare a reactive monomer mixture, which consists of 77% by weight of the formulation listed in Table 3 and 23% by weight of diluent D3O. Manufacture lenses from this reactive monomer mixture on a pilot production line, using a double-sided 395 nm LED with an intensity of 1.5 mW / cm 2 to cure the lenses for 4 minutes, and then use a double-sided 395 nm LED with an intensity of 5 mW / cm 2 to cure the lenses for 4 minutes. Package the lenses in a standard blister pack with a borate buffered wetting solution containing approximately 50 ppm methylcellulose; and sterilize the lenses (Example 4A) at 121 °C for approximately 18 minutes.

[0410] Figure 3

[0411]

[0412] Example 4A (control lenses) were removed from their original blister packs and placed into separate glass vials containing 5 mL of borate buffered wetting solution. The vials containing these lenses were stored in a stability chamber at 89 °C for one month. Subsequently, the lens parameters, mechanical properties, and UV-VIS spectral properties (average percent transmission over the wavelength range) of these heat-treated lenses (Example 4B) were measured and compared to the control lenses. These data are shown in Tables 4 - 6. Standard deviations are shown in parentheses. The UV-VIS spectra of Example 4A and Example 4B are shown in Table 4. Lens Parameters .

[0413] The blister packs containing Example 4A lenses were placed in a controlled photostability chamber (foil side down, bowl side up so that the lenses in the bowl are exposed to light). The photostability chamber was maintained at 25 °C ± 2 °C and ambient relative humidity. Then these lenses were sequentially exposed to 1.5 million lux-hours of visible light (168.8 hours of exposure) and 259.4 watt-hours / m 2 of ultraviolet light (16.2 hours of exposure). Subsequently, the lens parameters, mechanical properties, and UV-VIS spectral properties (average percent transmission over the wavelength range) of these photo-stress-treated lenses (Example 4C) were measured and compared to the control lenses. These data are shown in Tables 4 - 7. Standard deviations are shown in parentheses. The UV-VIS spectrum of Example 4C is also shown in Lens Parameters .

[0414] Example 4A

[0415] Example 4B Example 4C Lens Diameter (mm) Base Curve Radius (mm) Center Thickness (mm) 14.44(0.01) 14.50(0.01) 14.45(0.011 PW2EQD(D) 8.61(0.01) 8.59(0.07) 8.59(0.01) RMS_65 (μm) 0.085(0.002) 0.086(0.001) 0.086(0.001) Table 5. Mechanical Properties -0.07 -0.02 -0.006 Table 6. Spectral Properties 0.03 0.06 0.03

[0416] Table 7. Thermal and Photostability at the Visible Light Absorption Maximum

[0417]

[0418] ​

[0419]

[0420] ​

[0421]

[0422] 1 At the maximum of visible light absorption

[0423] Chromophores having the chemical substructure of formula I (such as compound B), as shown by the minor changes in lens parameters, mechanical properties and UV-VIS transmission spectra after heat treatment or light exposure, exhibit thermal and photo-stability in contact lenses while substantially mimicking the UV-VIS spectrum of macular pigment.

Claims

1. A compound, the compound being:

2. The compound according to claim 1, the compound having a maximum full width at half maximum (FWHM) of at least 35 nm and at most 100 nm at the maximum visible light absorption, wherein the compound is photostable.

3. The compound according to claim 2, wherein the maximum visible light absorption is between 440 nm and 470 nm.

4. The compound according to claim 2 or 3, wherein the FWHM at the maximum visible light absorption is at least 40 nm and at most 95 nm.

5. The compound according to claim 2 or 3, wherein the photostability comprises an absorbance loss of no more than 20% at the maximum visible light absorption.

6. The compound according to claim 1 or 2, the compound having a maximum full width at half maximum (FWHM) of at least 35 nm and at most 100 nm at the maximum visible light absorption, wherein the compound is more photostable than macular pigment.

7. The compound according to claim 1 or 2, the compound having at least 7740 L.mol -1 .cm -1 of molar extinction coefficient.

8. An ophthalmic device, the ophthalmic device comprising the compound according to any one of claims 1 to 7.

9. A contact lens or an intraocular lens, the contact lens or the intraocular lens being a polymerization product of a reactive mixture, the reactive mixture comprising: (a) monomers suitable for manufacturing an ophthalmic device; and (b) the compound according to any one of claims 1 to 7.

10. An eyeglass lens or a sunglass lens, the eyeglass lens or the sunglass lens comprising: (a) a mineral material or an organic material or a combination thereof, and (b) the compound according to any one of claims 1 to 7.

11. A method for preparing a compound of the following formula: The method comprising: Provided are N-substituted acridones: 2-methoxy-10-propylacridin-9(10H)-one or 2-methoxy-10-butylacridin-9(10H)-one; treating the N-substituted acridones with triphenylphosphine dibromide and N-2-methacryloyloxyethyl-2-cyanoacetamide; and isolating the compound.

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