Topical veterinary products and related methods

Abstract

This invention is directed to a veterinary pour-on formulation comprising a UV absorbing molecule that is used to stabilize the colour of the formulation and reduce the degradation of the active pharmaceutical ingredient.

Description

[0001] Topical Veterinary Products and Related Methods TECHNICAL FIELD The present invention pertains to the field of pharmaceutical formulations, specifically to the development of topical veterinary products. BACKGROUND Topical applied pour-on formulations are particularly popular especially for the administration to livestock animals because they require minimal handling of the animals and allow treatment of large flocks. International patent applications WO2016 / 168056, WO2016 / 168058, WO 2016 / 168059 and WO2018 / 071327 disclose certain cyclopropyl amide compounds as having insecticidal and acaricidal activity and therefore, being useful in controlling agricultural plant pests. WO2022 / 161972 discloses cyclopropyl amide compounds, compositions, and methods for controlling parasitic infestations of animals. SUMMARY OF INVENTION The present invention is related in a first aspect to a topical pour-on formulation, comprising a solvent and a compound of Formula (I) as described in the claims, characterized in that the formulation comprises a colorant and an UV absorbing molecule. The invention is also directed to a veterinary product with such topical pour-on formulation in a semi-transparent or transparent container as primary packaging. DESCRIPTION OF DRAWINGS Figure 1: Images of Formulations before and after Photo-exposure This figure presents the images of the three different formulations - control, inventive, and comparative - before and after photo-exposure. The images visually demonstrate the effect of photo-exposure on the color and stability of the formulations. The control and comparative formulations show significant color change after photo-exposure, indicating instability, while the inventive formulation maintains its color, demonstrating the effectiveness of the UV absorbing molecule in stabilizing the color. DEFINITIONS In accordance with this detailed description, the following abbreviations and definitions apply. It must be noted that as used herein, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Terms used herein will have their customary meaning in the art unless specified otherwise. In this disclosure and in the claims, terms such as "comprises," "comprising," "containing" and "having" and the like can mean "includes," "including," and the like; "consisting essentially of or "consists essentially" likewise is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments. As used in the specification and claims, the terms "about" and "approximately" designate that a value is within a statistically meaningful range. Such a range can be typically within 20%, more typically still within 10%, and even more typically within 5% of a given value or range. The allowable variation encompassed by the terms "about" and "approximately" depends on the particular system under study and can be readily appreciated by one of ordinary skill in the art. Concentration ranges for the components of the disclosed formulations are expressed as % weight per volume of the final formulation unless otherwise stated. “Pharmaceutically acceptable” as used in this application, for example with reference to salts and formulation components includes “dermatologically acceptable” for topical dosage forms, and “veterinary acceptable,” and thus includes both human and animal applications independently. A “pour-on formulation” is a formulation that is adapted for applying the formulation to a specific location of the skin or coat, such as on the neck or backbone of the animal. This may be achieved by, for example, applying a swab or drop of the pour-on formulation to a relatively small area of the recipient animal's skin or coat (i.e., generally no greater than about 10% of the animal recipient's skin or coat). A ”multi-dose container” vial, bottle or other container contains liquid medication intended for administration to animals that contains more than one dose of medication. This requires the formulations according to the invention to be stable, this means that the active ingredient does not substantially degrade, upon storage in unopened condition and during multiple rounds of opening and closing of the multi-dose container. “Livestock animals” are animals are kept for meat and milk or wool or alternatively as working animals, especially ruminants such as cattle, sheep, goat, deer, camels, lamas. DESCRIPTION OF EMBODIMENTS The invention is particularly concerned with the photostability of topically applied pour-on formulations for animals, especially for livestock animals, which are typically sold as veterinary products in multi-dose transparent or semi-transparent containers or bottles. Especially for livestock animals, the more advantageous treatment at the treatment at the same time of a group of animals, or to all animals in a single stable, pen, net, group, house, or farm. The invention is especially advantageous when the livestock animals are bovine animals such as cattle. Especially preferred are beef cattle, i.e., cattle animals kept for meat or alternatively dairy cows. In another embodiment the animals are sheep. In another embodiment the animals are goats. Pour-on formulations are ready-to-use formulations intended to be applied topically and locally on the animal with the assistance of a suitable device by pouring one or several lines or in a spot-on along the dorsal midline (back) or shoulder of an animal. More typically, the formulation is applied by pouring it along the back of the animal, following the spine. Such pour-on administration permits directed application of a small amount of formulation onto the skin of the animal being treated whereby the active ingredient migrates (spreads) as to protect the whole external surface of the animal and if desired, the active ingredient (depending on the molecule) enters the body through permeation of the skin and acts transdermally. Typically for cattle animals a volume of 30 ml or less and sheep animals 10 ml or less per animal of the pour-on formulation is administered to a single animal. Typically, the pour-on formulation is a liquid and has a sufficient viscosity that prevents run-off from the animals’ fur or skin by sufficient adherence to the fur / skin of the animal after administration but can be easy administered, e.g., expelled the correct amount from the container at various temperatures. Liquid dosage forms that would be suitable as a pour-on formulation are generally solutions, suspensions, or emulsions. The liquid may be aqueous, oily, or both. Many (veterinary) active pharmaceutical ingredients (APIs) that can be used in pour-on formulations are susceptible to photodegradation, which can lead to a loss of potency and / or the formation of harmful impurities. Therefore, it is essential to address the photostability of a formulation during product development and packaging design. Ensuring the photostability of a veterinary product is crucial to maintaining its efficacy, safety, and quality throughout its shelf life.This is especially important for veterinary active ingredients that have low photostability, which means they can be easily degraded by exposure to light. This can result in a loss of potency and effectiveness of the product, which can ultimately impact the health of the animal. When it comes to storage of liquid veterinary formulations especially for those that have been identified as having low photostability, the material for bottles and containers for storage of such product is an important tool to address this problem. The low photostability of veterinary active ingredients is conventionally addressed by packaging of the veterinary product in specific material that protects it from light, such as colored bottles, or packaging that includes UV absorbing molecules or a secondary protective packaging. All these options regarding adjusted packaging add costs and / or have other downsides. Especially for multidose containers that include many individual doses for treatment of many animals, it is important that the farmer or veterinarian can easily recognize how many doses are left in the container. A transparent or semi-transparent bottle or other packaging facilitates this by visually allowing to check the remaining filling of the bottle. Glass is a material often recommended for packaging of veterinary medications, but it does not offer the same flexibility and durability that modern plastics provide. Polycarbonate is a popular material, as it is shatterproof and able to withstand high temperatures. Additionally, polycarbonate is transparent and resistant to chemicals commonly used in the medical field. Another option is polyethylene terephthalate (PET), a lightweight and cost-effective material. PET bottles provide good resistance to impact and can withstand a range of temperatures. Another material that is commonly used for the storage of liquid medicaments is high-density polyethylene (HDPE). HDPE bottles are known for their toughness, durability, and their ability to resist chemicals. The material also offers a good level of moisture protection, which is important for medicines that require a humidity- controlled environment. HDPE bottles are semi-transparent and are commonly used for packaging liquid medications. Like other plastics, HDPE bottles can be manufactured in a range of shapes and sizes, making them a versatile option for packaging a variety of medicaments. Ultimately, the choice of material depends on the specific medication's storage requirements, regulations, and cost constraints. On the other hand, colorants are used in pharmaceutical formulations to enhance the appearance of the product. Especially for formulations for livestock animals such as pigs, or cattle or sheep colorants can be included in veterinary formulations with the aim of marking the animals visually that have been already treated. This helps to discriminate treated from untreated animals in a large flock and ensures that the farmer or veterinarian applies the medicament to all animals in a group or pen. This is especially useful for veterinary pharmaceutical pour-on formulations that are applied topically. Thereby treated animals can be detected from the distance by recognizing the color on the back of the animal easily. Coloring of the pharmaceutical formulations helps dosing accuracy e.g., to accurately measure the correct volume of the product in a bottle. Some of the colorants are however also susceptible to photodegradation and either the coloring disappears or changes during storage or after application. This is an undesired effect. The current invention addresses the challenge of maintaining both the color and the chemical stability of the active pharmaceutical ingredient (API) in pour-on formulations when they are exposed to sunlight. In the example embodiment, we demonstrated that use of a UV absorbing molecule can be used to both stabilize the color of the formulation as well as reduce the degradation of the API. The method that was used to test the photostability of the color and chemical stability is one cycle as described in ICH method Q1B using a Suntest CPS+ II chamber. It was also shown that typical antioxidant additives alone, such as BHT, were not suitable to avoid degradation of both the active ingredient of Formula (I) and the color. The color was measured using a Hach Lange Colorimeter, change in color was calculated using a specific formula. Finally, the test samples were characterized by liquid chromatography to determine both the degradation of the API and formation of photo-degradation products. These data show that the formulation of the invention is photo stable and that UV absorbing molecules are adequate to photo-stabilize both the color and API in a topical pour-on formulation. In the formulation according to the invention the active pharmaceutical ingredient is a compound of Formula (I) Formula (I) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein A1is CR5, N=O, or N; A2is CR6, N=O, or N; A3 is CR7, N=O, or N; A4is CR8, N=O or N; A5is CR9, N=O or N ; wherein no more than 3 of A1, A2, A3, A4, A5 are N or N=O; R1is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2; R2is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2and S-(Halo)5; R3is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2and S-(Halo)5; R4is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2 and S-(Halo)5 ; R5is selected from the group consisting of H, F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)NHphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R6is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)NHphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R7is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)NHphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R8is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)NHphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R9is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)NHphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; or R6and R7together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of -CH2-, -CH=, =CH-,-N=, =N-, -NH-, -O-, -S(O)-, -S(O)2- and -S-, wherein the ring formed by R6and R7is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, Cl, Br, I, CN, NO2, and =O; or R7and R8together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of -CH2-, -CH=, =CH-,-N=, =N-, -NH-, -O-, -S(O)-, -S(O)2- and - S-, wherein the ring formed by R7and R8is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, Cl, Br, I, CN, NO2, and =O; R10is selected from the group consisting of H, (C1-C6)alkyl, C3-C6)cycloalkyl), (C1- C6)alkyloxy-(C1-C6)-alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1- C6)alkyloxy-(C1-C6)haloalkyl, C1-C6)alkyloxy-(C2-C6)-alkenyl, (C1-C6)alkyl-(C3- C6)cycloalkyl, heterocycle, aryl and (C1-C6)alkylphenyl; R11is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2; R12is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2; R13is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, CHO, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, (C1-C6)haloalkyl-S(O)2NH2, and triazolyl; R14is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2; R15is selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2- C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)alkoxy(C1-C6)alkyl, C(=O)(C1-C6)alkyl, and (C1-C6)alkoxyC(=O)(C1-C6)alkyl H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl; wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. Throughout the description embodiments are described. it is to be understood that it is envisioned that these embodiments can be combined, e.g. an embodiment describing an R3and an embodiment describing R8. However for brevity these combined embodiment are not explicitly described. In a preferred embodiment at least one of the following selections is made: R1is selected from the group consisting of H F, and Cl; and / or R2is selected from the group consisting of H, F, and Cl; and / or R3is selected from the group consisting of H, F, and Cl; and / R4is selected from the group consisting of H, F, and Cl. In another preferred embodiment at least 1 of A1, A2, A3, A4, A5is N, preferably 1 of A1, A2, A3, A4, A5 is N, preferably A1 or A2 is N. In another preferred embodiment at least one of the following selections is made: R5is selected from the group consisting of H F, Cl, Br, and I; and / or R6is selected from the group consisting of H, F, and Cl, Br, and CH3; and / or R7is selected from the group consisting of H F, Cl, Br, and I; and / or R8is selected from the group consisting of H, F, Cl, and Br, and CH3; and / or R9is selected from the group consisting of H F, Cl, Br, and I. In another preferred embodiment at least two of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I, more preferably F or Cl. In another preferred embodiment R13is selected from the group consisting of H, F, Cl, CF3 and CH3,,preferably R13is Cl or F. In an embodiment of the invention and / or embodiments thereof, R1is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3- C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy. In an embodiment of the invention and / or embodiments thereof, R1is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3- C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C3- C6)halocycloalkyl, (C2-C6)haloalkenyl, (C1-C6)haloalkoxy of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkoxy. In an embodiment of the invention and / or embodiments thereof, R1is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3- C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C1- C6)haloalkyl of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C1-C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R1is H. In an embodiment of the invention and / or embodiments thereof, R2is selected from the group consisting H, F, Cl, Br, I, CN, (C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)haloalkyl, (C1-C6)haloalkoxy, and S-(Halo)5.In an embodiment of the invention and / or embodiments thereof, R2is selected from the group consisting of H, F, Cl, Br, CN, (C1-C6)alkyl, (C1-C6)haloalkyl and S- (Halo)5.In an embodiment of the invention and / or embodiments thereof, R2is selected from the group consisting of H, F, Cl, Br, CN, CH3, CHF2, CF3, OCHF2 and S- (Halo)5. In an embodiment of the invention and / or embodiments thereof, R2is selected from the group consisting of H, F, Cl. In an embodiment of the invention and / or embodiments thereof, R2is selected from the group consisting of F, and Cl. In an embodiment of the invention and / or embodiments thereof, R2is Cl. In an embodiment of the invention and / or embodiments thereof, R3is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C2-C6)alkenyl, (C2- C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2-C6)haloalkenyl, and (C1-C6) haloalkoxy. In an embodiment of the invention and / or embodiments thereof, R3is selected from the group consisting of H, F, Cl, Br, I, CH3, CF3, CHF2, OCF3, OCH3, CH=CHF, C≡C, CH=CH2. In an embodiment of the invention and / or embodiments thereof, R3is selected from the group consisting of H, F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, R3is selected from the group consisting of H, F, Cl, Br. In an embodiment of the invention and / or embodiments thereof, R3is selected from the group consisting of H, F, and Cl. In an embodiment of the invention and / or embodiments thereof, R3is H or F. In an embodiment of the invention and / or embodiments thereof, R3is H. In an embodiment of the invention and / or embodiments thereof, R3is F. In an embodiment of the invention and / or embodiments thereof, R4is selected from the group consisting of H, F, Cl, Br, I, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2- C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2-C6)haloalkenyl, (C1-C6)haloalkoxy, and S-(Halo)5. In an embodiment of the invention and / or embodiments thereof, R4is selected from the group consisting of H, F, Cl, Br, (C1-C6)alkyl, (C1-C6)haloalkyl, (C2- C6)alkenyl, (C2-C6)alkynyl (C1-C6)alkoxy, (C2-C6)haloalkenyl, and S-(Halo)5. In an embodiment of the invention and / or embodiments thereof, R4is selected from the group consisting of H, F, Cl, Br, CH3, CF3, OCH3, CH=CHF, C≡C, CH=CH2 and SF5. In an embodiment of the invention and / or embodiments thereof, R4is selected from the group consisting of H, F, Cl, and Br. In an embodiment of the invention and / or embodiments thereof, R4is selected from the group consisting of H, F, and Cl. In an embodiment of the invention and / or embodiments thereof, R4is Cl. In an embodiment of the invention and / or embodiments thereof, R4is selected from the group consisting of F, and Cl. In an embodiment of the invention and / or embodiments thereof, R4is H. In an embodiment of the invention and / or embodiments thereof, 0, 1 or 2 of A1, A2, A3, A4, A5 is N In an embodiment of the invention and / or embodiments thereof, the compound is a prodrug and at least one of A1, A2, A3, A4, A5is N=O. In an embodiment of the invention and / or embodiments thereof, 0, 1 or 2 of A1, A2, A3, A4, A5 is N=O In an embodiment of the invention and / or embodiments thereof, A1is CR5or N;A2is CR6or N;A3is CR7or N;A4is CR8or N;A5is CR9or N; wherein no more than 3 of A1, A2, A3, A4, A5 are N. In an embodiment of the invention and / or embodiments thereof, A1is CR5or N; A2is CR6or N;A3is CR7or N;A4is CR8or N;A5is CR9or N; wherein 0 or 1 of A1, A2, A3, A4, A5 are N. In an embodiment of the invention and / or embodiments thereof, A1is CR5or N; A2is CR6or N,A3is CR7;A4is CR8;A5is CR9; wherein 0 or 1 of A1, or A2are N. In an embodiment of the invention and / or embodiments thereof, A1is CR5or N; A2is CR6,A3is CR7;A4is CR8;A5is CR9. In an embodiment of the invention and / or embodiments thereof, A1 is N; A2 is CR6,A3 is CR7;A4 is CR8;A5 is CR9; In an embodiment of the invention and / or embodiments thereof, R5is selected from the group consisting of H, F, Cl, Br, I, CN, NO2, NH2, =O, NH(C1-C6)alkyl, N((C1-C6)alky)2, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, NHC(=O)R10, N(C1- C6)alkyl-C(=O)lR10, C(=O)(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)haloalkenyl, and C(=O)-O-(C1-C6)alkyl. In an embodiment of the invention and / or embodiments thereof, R5is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C1-C6)alkoxy, and (C1- C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R5is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, and CF3. In an embodiment of the invention and / or embodiments thereof, R5is selected from the group consisting of H, F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, R5is selected from the group consisting of H, F, and Cl. In an embodiment of the invention and / or embodiments thereof, R5is H or F. In an embodiment of the invention and / or embodiments thereof, R5is F. In an embodiment of the invention and / or embodiments thereof, R6is selected from the group consisting of H, F, Cl, Br, I, CN, NO2, NH2, =O, NH(C1-C6)alkyl, N((C1-C6)alky)2, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, NHC(=O)R10, N(C1- C6)alkyl-C(=O)lR10, C(=O)(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)haloalkenyl, and C(=O)-O-(C1-C6)alkyl. In an embodiment of the invention and / or embodiments thereof, R6is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)haloalkyl, (C2-C6)alkenyl, and (C2-C6)haloalkenyl. In an embodiment of the invention and / or embodiments thereof, R6is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R6is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R6is selected from the group consisting of H, F, Cl, Br, and CH3. In an embodiment of the invention and / or embodiments thereof, R6is selected from the group consisting of H, F, Cl, and CH3. In an embodiment of the invention and / or embodiments thereof, R6is H or F. In an embodiment of the invention and / or embodiments thereof, R6is H. In an embodiment of the invention and / or embodiments thereof, R7is selected from the group consisting of H, F, Cl, Br, I, CN, NO2, NH2, =O, NH(C1-C6)alkyl, N((C1-C6)alky)2, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, NHC(=O)R10, N(C1- C6)alkyl-C(=O)lR10, C(=O)(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)haloalkenyl, and C(=O)-O-(C1-C6)alkyl. In an embodiment of the invention and / or embodiments thereof, R7is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)haloalkyl, (C2-C6)alkenyl, and (C2-C6)haloalkenyl. In an embodiment of the invention and / or embodiments thereof, R7is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R7is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R7is selected from the group consisting of H, F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, R7is selected from the group consisting of H, F, and Cl. In an embodiment of the invention and / or embodiments thereof, R7is H or F. In an embodiment of the invention and / or embodiments thereof, R7is F. In an embodiment of the invention and / or embodiments thereof, R8is selected from the group consisting of H, F, Cl, Br, I, CN, NO2, NH2, =O, NH(C1-C6)alkyl, N((C1-C6)alky)2, (C1-C6)alkyl, (C1-C6)alkoxy, C1-C6)haloalkyl, NHC(=O)R10, N(C1- C6)alkyl-C(=O)lR10, C(=O)(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)haloalkenyl, and C(=O)-O-(C1-C6)alkyl. In an embodiment of the invention and / or embodiments thereof, R8is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)haloalkyl, (C2-C6)alkenyl, and (C2-C6)haloalkenyl. In an embodiment of the invention and / or embodiments thereof, R8is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R8is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R8is selected from the group consisting of H, F, Cl, Br, and CH3. In an embodiment of the invention and / or embodiments thereof, R8is selected from the group consisting of H, F, Cl, and CH3. In an embodiment of the invention and / or embodiments thereof, R8is H or F. In an embodiment of the invention and / or embodiments thereof, R8is H. Compound and use according to any of the preceding claims, wherein R9is selected from the group consisting of H, F, Cl, Br, I, CN, NO2, NH2, =O, NH(C1- C6)alkyl, N((C1-C6)alky)2, (C1-C6)alkyl, (C1-C6)alkoxy, C1-C6)haloalkyl, NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10, C(=O)(C1-C6)alkyl, (C2-C6)alkenyl, (C2- C6)haloalkenyl, and C(=O)-O-(C1-C6)alkyl. In an embodiment of the invention and / or embodiments thereof, R9is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)haloalkyl, (C2-C6)alkenyl, and (C2-C6)haloalkenyl. In an embodiment of the invention and / or embodiments thereof, R9is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R9is selected from the group consisting of H, F, Cl, Br, I, CH3, OCH3, CH=CHF, CH=CH, and CF3. In an embodiment of the invention and / or embodiments thereof, R9is selected from the group consisting of H, F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, R9is selected from the group consisting of H, F, and Cl. In an embodiment of the invention and / or embodiments thereof, R9is H or F. In an embodiment of the invention and / or embodiments thereof, R9is H. In an embodiment of the invention and / or embodiments thereof, R9is F. In an embodiment of the invention and / or embodiments thereof, at least two of R5, R6, R7, R8, R9, are F. In an embodiment of the invention and / or embodiments thereof, at least two of R5, R7, R9, are F. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, and Br. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, and Cl. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R6, R7, R8, R9, is F. In an embodiment of the invention and / or embodiments thereof, at least two of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, and Br. In an embodiment of the invention and / or embodiments thereof, at least two of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, and Cl. In an embodiment of the invention and / or embodiments thereof, at least two of R5, R6, R7, R8, R9, is F. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R6, R7is a substituent selected from the group consisting of F, Cl, and Br. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R6, R7is a substituent selected from the group consisting of F, and Cl. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R6, R7is F. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R7is a substituent selected from the group consisting of F, Cl, and Br. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R7is a substituent selected from the group consisting of F, and Cl. In an embodiment of the invention and / or embodiments thereof, at least one of R5, R7is F. In an embodiment of the invention and / or embodiments thereof, R5and R7are each a substituent selected from the group consisting of F, Cl, and Br. In an embodiment of the invention and / or embodiments thereof, R5and R7are each a substituent selected from the group consisting of F, and Cl. In an embodiment of the invention and / or embodiments thereof, R5and R7are each F. In an embodiment of the invention and / or embodiments thereof, R6and R7together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of - CH2-, -CH=, =CH-,-N=, =N-, -NH-, and -O-. In an embodiment of the invention and / or embodiments thereof, R6and R7together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of - CH2-, -CH=, =CH-,-N=, =N-, and -NH-. In an embodiment of the invention and / or embodiments thereof, the ring formed by R6and R7is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, Cl, Br, I, CN. In an embodiment of the invention and / or embodiments thereof, the ring formed by R6and R7is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, and Cl. In an embodiment of the invention and / or embodiments thereof, the ring formed by R6and R7is optionally substituted with one or more substituents of selected from the group consisting of CH3, F, and Cl. In an embodiment of the invention and / or embodiments thereof, the ring formed by R6and R7is not substituted. In an embodiment of the invention and / or embodiments thereof, R7and R8together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of - CH2-, -CH=, =CH-,-N=, =N-, -NH-, and -O-. In an embodiment of the invention and / or embodiments thereof, R7and R8together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of - CH2-, -CH=, =CH-,-N=, =N-, and -NH-. In an embodiment of the invention and / or embodiments thereof, the ring formed by R7and R8is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, Cl, Br, I, and CN. In an embodiment of the invention and / or embodiments thereof, the ring formed by R7and R8is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, and Cl. In an embodiment of the invention and / or embodiments thereof, the ring formed by R7and R8is optionally substituted with one or more substituents of selected from the group consisting of CH3, F, and Cl. In an embodiment of the invention and / or embodiments thereof, the ring formed by R7and R8is not substituted. In an embodiment of the invention and / or embodiments thereof, R10is selected from the group consisting H, (C1-C6)alkyl, (C1-C6)alkyloxy-(C1-C6)-alkyl, (C2- C6)alkenyl, (C2-C6)alkynyl, ((C1-C6)haloalkyl, (C1-C6)alkyloxy-(C1-C6)haloalkyl, (C1- C6)alkyl-(C3-C6)cycloalkyl, tetrahydrofuranyl, piperidinyl, pyrrolidinyl, tetrahydrothiophenyl, thianyl, phenyl, and (C1-C6)alkylphenyl. In an embodiment of the invention and / or embodiments thereof, R10is selected from the group consisting (C1-C6)alkyl, (C1-C6)alkyloxy-(C1-C6)alkyl, (C2- C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)alkyloxy-(C1-C6)haloalkyl, (C1- C6)alkyl-(C3-C6)cycloalkyl, tetrahydrofuranyl, and phenyl. In an embodiment of the invention and / or embodiments thereof, R11is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3- C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2- C6)haloalkenyl, (C1-C6)haloalkoxy, and (C1-C6)alkyl-S(O)2NH2. In an embodiment of the invention and / or embodiments thereof, R11is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, and (C1-C6)alkyl. In an embodiment of the invention and / or embodiments thereof, R11is selected from the group consisting of H, F, Cl, Br, I, and CH3.In an embodiment of the invention and / or embodiments thereof, R11is selected from the group consisting of H, F, Cl, and CH3. In an embodiment of the invention and / or embodiments thereof, R11is H. In an embodiment of the invention and / or embodiments thereof, R12is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3- C6)cycloalkyl, (C2-C6)alkenyl (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2- C6)haloalkenyl, (C1-C6)haloalkoxy, and (C1-C6)alkyl-S(O)2NH2. In an embodiment of the invention and / or embodiments thereof, R12is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C2- C6)alkenyl; (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2-C6)haloalkenyl, and (C1- C6)haloalkoxy. In an embodiment of the invention and / or embodiments thereof, R12is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C1-C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R12is selected from the group consisting of H, F, Cl, CH3and CF3.In an embodiment of the invention and / or embodiments thereof, R12is H or F. In an embodiment of the invention and / or embodiments thereof, R12is H. In an embodiment of the invention and / or embodiments thereof, R13is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, CHO, (C1-C6)alkyl, (C3- C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2- C6)haloalkenyl, (C1-C6)haloalkoxy, (C1-C6)alkyl-S(O)2NH2and triazolyl. In an embodiment of the invention and / or embodiments thereof, R13is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C2- C6)alkenyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2-C6)haloalkenyl, and (C1- C6)haloalkoxy. In an embodiment of the invention and / or embodiments thereof, R13is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, and (C1-C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R13is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, (C1-C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R13is selected from the group consisting of H, F, Cl, CH3 and CF3. In an embodiment of the invention and / or embodiments thereof, R13is Cl or F. In an embodiment of the invention and / or embodiments thereof, R13is Cl. In an embodiment of the invention and / or embodiments thereof, R14is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C3- C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2- C6)haloalkenyl, (C1-C6)haloalkoxy, and (C1-C6)alkyl-S(O)2NH2. In an embodiment of the invention and / or embodiments thereof, R14is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1-C6)alkyl, (C2- C6)alkenyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C2-C6)haloalkenyl, and (C1- C6)haloalkoxy. In an embodiment of the invention and / or embodiments thereof, R14is selected from the group consisting of H, F, Cl, Br, I, (C1-C6)alkyl, and (C1-C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R14is selected from the group consisting of H, F, Cl, CH3 and CF3. In an embodiment of the invention and / or embodiments thereof, R14is selected from the group consisting of H and F. In an embodiment of the invention and / or embodiments thereof, R14is H. In an embodiment of the invention and / or embodiments thereof, R15is selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, and (C1-C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R15is selected from the group consisting of H, (C1-C6)alkyl, and (C1-C6)haloalkyl. In an embodiment of the invention and / or embodiments thereof, R15is selected from the group consisting of H, CH3, and CF3. In an embodiment of the invention and / or embodiments thereof, R15is selected from the group consisting of H, and CH3. In an embodiment of the invention and / or embodiments thereof, R15is H. In another preferred embodiment R1is selected from the group consisting of H F, and Cl; R2is selected from the group consisting of H, F, and Cl; R3is selected from the group consisting of H, F, and Cl; R4is selected from the group consisting of H, F, and Cl; R5is selected from the group consisting of H F, Cl, Br, and I; R6is selected from the group consisting of H, F, and Cl, Br, and CH3; R7is selected from the group consisting of H F, Cl, Br, and I; R8is selected from the group consisting of H, F, Cl, and Br, and CH3; R9is selected from the group consisting of H F, Cl, Br, and I; R11is H; R12is selected from the group consisting of H, F, CL, CH3, CF3; R13is selected from the group consisting of H, F, Cl, CF3 and CH3; R14is H or F; R15is selected from the group consisting of H and CH3; and wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In another preferred embodiment R1is H; R2is selected from the group consisting of H, F, and Cl; R3is selected from the group consisting of H, Cl, F, and Br; R4is H, F, Cl; R5is selected from the group consisting of H F, and Cl; R6is selected from the group consisting of H, F, and Cl, and CH3; R7is selected from the group consisting of H F, and Cl; R8is selected from the group consisting of H, F, Cl, and CH3; R9is selected from the group consisting of H F, and Cl; R11is H; R12is selected from the group consisting of H, F and Cl; R13is selected from the group consisting of H, F, and Cl; R14is H; R15is selected from the group consisting of H and CH3; and wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (II) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I, wherein R2, R3, R4, R5, R6, R7, R8, R9,R12, R13, R14, R15, A1, A2, A3, A4, and A5 are defined as elsewhere in this description. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (III) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R5, R6, R7, R8, R9,R13, R14, R15, A1, A2, A3, A4, and A5are defined as elsewhere in this description, wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (IV) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R5, R6, R7, R8, R9,R12, R13, R14, A1, A2, A3, A4, and A5are defined as elsewhere in this description and wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (V) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R5, R6, R7, R8, R9,R12, R13, R15, A1, A2, A3, A4, and A5are defined as elsewhere in this description and wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (VI) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R5, R6, R7, R8, R9, R13, A1, A2, A3, A4, and A5 are defined as elsewhere in this description and wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (VII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, R14, R15, A2, A3, A4, and A5 are defined as elsewhere in this description and wherein at least one of R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (VIII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R5, R7, R8, R9, R13, R14, R15, A1, A3, A4, and A5 are defined as elsewhere in this description and wherein at least one of R5, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (IX)

[0002] and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R6, R7, R8, R9, R13, A2, A3, A4, and A5 are defined as elsewhere in this description and wherein at least one of R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (X) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R5, R7, R8, R9, R13, A1, A3, A4, and A5 are defined as elsewhere in this description and wherein at least one of R5, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XI) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIV) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIVa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XV) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVI) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVIII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVIIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XVIIIb) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIX) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XIXa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XX) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXI) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIV) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIVa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXV) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXVa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXVI) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXVIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXVII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXVIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXVIII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXVIIIa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIX) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXIXa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXX) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In a particular embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXXa) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXXI) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R6, R8, R12, R13, R14, and R15, are defined as elsewhere in this description. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXXII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R6, R8, R13, R14, and R15are defined as elsewhere in this description. In an embodiment of the invention and / or embodiments thereof, the invention is directed to a compound of formula (XXXIII) and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein R2, R3, R4, R6, R8, and R13are defined as elsewhere in this description. In an especially preferred embodiment, the compound of Formula (XXVa) is F .(Compound A) In one embodiment the concentration of the active ingredient in the formulation is between about 0.1 and about 5% by weight of the total formulation. In another embodiment the concentration is between about 0.5% and about 2% by weight of the total formulation, preferably about 1% by weight of the total formulation. The active pharmaceutical ingredient for use in the current invention is preferably a veterinary active ingredient that has been identified as having low photostability. An additional constituent for the formulation according to the invention is a UV absorbing molecule. One or more UV absorbing molecules can be present. UV absorbing molecules are compounds used to protect light-sensitive compounds from ultraviolet radiation's harmful effects. These UV absorbing molecules absorb UV light and convert it into heat, reducing its impact on the surrounding materials. Examples of UV absorbing molecules include benzophenone and its derivatives such as bis-benzophenone and substituted benzophenones, oxybenzone, and octyl methoxycinnamate. In the present invention, it is preferred that the UV absorbing molecule in the formulation of the invention is selected from the group consisting of one or more selected from benzophenone compound(I), cyanoacrylate compound (II), benzotriazole compound (III) and salicylic acid compound (IV) Examples of UV absorbers include the following compounds. Benzophenone Compounds: 2,4-dihydroxybenzophenone, 2-hydroxy-4- methoxybenzophenone, 2-hydroxy-4-octoxybenzophenone, 2-hydroxy-4- dodecyloxybenzophenone, 2,2′-dihydroxy-4-methoxybenzophenone, 2,2′- dihydroxy-4,4′-dimethoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5- sulfonic acid trihydrate, 4-benzyloxy-2-hydroxybenzophenone, 2,2′,4,4′- tetrahydroxybenzophenone, 1,4-bis(4-benzoyl-3-hydroxyphenoxy)butane, ; bis(2- methoxy-4-hydroxy-5-benzoylphenyl)methane, oxybenzone or dioxibenzone. Cyanoacrylate Compounds: 2-ethylhexyl-2-cyano-3,3′-diphenylacrylate, ethyl-2- cyano-3,3′-diphenylacrylate. Benzotriazole Compounds: 2-(2-hydroxy-5-methylphenyl)-2H-benzotriazole, 2-(2- hydroxy-5-tert-butylphenyl)-2H-benzotriazole, 2-(2-hydroxy-3,5-di-tert- butylphenyl)-2H-benzotriazole, 5-chloro-2-(2-hydroxy-3-tert-butyl-5-methylphenyl)- 2H-benzotriazole, 5-chloro-2-(2-hydroxy-3,5-di-tert-butylphenyl)-2H-benzotriazole, 2-2,2′-methylenebis-[4-(1,1,3,3-tetramethylbutyl)-6-(2H-benzotriazole-2- yl)phenol](2-hydroxy-3,5-di-tert-amylphenyl)-2H-benzotriazole, 2-(2H- benzotriazole-2-yl)-4-methyl-6-(3,4,5,6-tetrahydrophthalimidylmethyl)phenol, 2,2′- methylenebis[4-(1,1,3,3-tetramethylbutyl)-6-(2H-benzotriazole-2-yl)phenol], 2-(2- hydroxy-4-octoxyphenyl)-2H-benzotriazole, 2-(2-hydroxy-5-tert-octylphenyl)-2H- benzotriazole, 2-(2-hydroxy-5-methacryloxyphenyl)-2H-benzotriazole, 2-[2- hydroxy-3,5-bis(α,α′-dimethylbenzyl)phenyl]-2H-benzotriazole. Salicylic Acid Compounds: phenyl salicylate,p-tert-butylphenyl salicylate, or p- octylphenyl salicylate. Among them, BP-8, also known as benzophenone-8 or dioxybenzone is preferred. Alternatively, BP3 also known as oxybenzone or benzophenone -3 is used. The concentration of UV absorbing molecules in a pharmaceutical formulation can vary depending on the specific application and desired level of protection. Broadly speaking, the concentration of UV absorbers is typically between about 0.01% to about 2% by weight of the total formulation. However, in more specific applications narrower preferred ranges may apply. For example, between about 0.05% to about 1% by weight, or 0.1%. The exact concentration of UV absorbers in a specific formulation can be optimized based on several factors including the molecular properties of the active pharmaceutical ingredient (API) compound, the intended use of the product, and regulatory requirements. In a preferred embodiment, no other stabilizing compound is present in the topical pour-on formulation according to the invention, especially no antioxidant. Antioxidants are chemically reducing agents. They oxidize themselves and prevent oxidation of the API. Examples of antioxidants in pharmaceutical products are ascorbic acid, butylated hydroxy anisole (BHA), butylated hydroxyl toluene (BHT), cysteine, ascorbyl palmitate, sodium metabisulfite, propyl gallate and alpha tocopherol. An additional constituent for the formulation according to the invention is a coloring agent or colorant, such as a dye or pigment or a combination of different dyes or pigments that are preferably pharmaceutically acceptable. The presence of a colorant will support visual monitoring of the treated animals by detecting the coloring agent’s color on the back of the animal and support dosing accuracy, especially in multi-dose containers such as glass container or bottle, or a container made from polyethylene terephthalate (PET) or high-density polyethylene (HDPE), especially if the multi-dose container is semi-transparent. Colorants for use in the pour-on formulation of the present invention are those commonly known in the art. Such a coloring agent should of course be allowed for administration to food producing livestock animals. Suitable coloring agents are those allowed under the US Federal Food, Drug, and Cosmetic Act (FD&C) such as Brilliant blue FCF, (FD&C Blue n° 1), FD&C Yellow n° 5 or natural food dyes such as Chlorophyllin (green), or a mixture of any of the foregoing. Preferably the colorant is Brilliant blue FCF- FD&C Blue n° 1. The colorant for use in the current invention is preferably an ingredient that has been identified as having low photostability when used in the formulation according to the invention. The concentration of colorants in a pharmaceutical formulation can vary depending on the product's intended use and desired visual effect. Broadly speaking, the concentration of colorants in pharmaceutical formulations ranges from about 0.01% to about 1% by weight of the total product. An additional constituent for the formulation according to the invention is a pharmaceutically acceptable solvent. Solvents are an essential component in veterinary pour-on formulations as they aid in the dissolution of active ingredients and help to facilitate their easy application. Different classes of solvents can be used for this purpose, and the choice of solvent depends on several factors such as the active ingredient's solubility and compatibility with other excipients. Solvents must be chosen carefully and meet regulatory requirements to ensure their safety in pharmaceutical formulations. They should be biocompatible, non- reactive, and have a low toxicity profile to ensure that the animal remains healthy after application of the formulation. Non-limiting examples of suitable solvents include, but are not limited to water, pyrrolidone solvents (such as 2-pyrrolidone and N-methyl-2-pyrrolidone), glycol ethers (such as ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, and dipropylene glycol monoethyl ether), ethyl lactate, polyethylene glycols (PEG) with an average molecular weight between about 200 and 1000, PEG esters of carboxylic acids, dicarboxylic acids, and fatty acids, glycerol esters (such as triacetin and caprylic / capric triglycerides), glycerol ethers (such as glycerol formal), propylene glycol dicaprylate / dicaprate, lauryl lactate, diisopropyl adipate, acetyltributyl citrate, oleic acid, esters of diacids, ketones (such as acetone and methylisobutyl ketone), acetonitrile, C1-C12alcohols (such as benzyl alcohol, methanol, ethyl alcohol, isopropanol, and butanol), aromatic ethers (such as anisole), amides (such as dimethylacetamide, monomethylacetamide, and dimethylformamide), dimethyl sulfoxide (DMSO), ethylene glycol, propylene glycol, glycol carbonates (such as propylene carbonate and butylene carbonate), C1-C12 alkyl esters of carboxylic acids (such as butyl or octyl acetate and benzyl acetate), C1-C12alkyl esters of dicarboxylic acids, aryl esters (such as benzyl benzoate and ethyl benzoate), and diethyl phthalate or mixtures thereof. In one preferred embodiment the solvent is propylene glycol. Pour-on formulations of the invention comprising a solvent, UV absorbing molecule, colorant and a compound of formula (I) can be prepared using a general manufacturing process. First, all the ingredients are weighed and mixed thoroughly in a suitable vessel until a homogenous solution is obtained. The solvent is used to dissolve the active pharmaceutical ingredient. In case of a suspension or emulsion the components as described above are mixed until a homogeneous liquid formulation is obtained. The UV absorbing molecule and colorant are then added and mixed until they are fully dissolved. The final pour-on formulation is then filled into the multi dose container, especially preferred are semi-transparent HDPE bottles. The bottles are sealed to avoid air and water contamination and are labeled with relevant product information. Another aspect of the invention is a veterinary product with the topical pour-on formulation as described in this document in a semi-transparent or transparent multi-dose container as primary packaging, from which accurate single dose aliquots of the formulations may be administered to animals. The multi-dose container can be a glass container or bottle, or a container made from polyethylene terephthalate (PET). Another preferred material is high-density polyethylene (HDPE). In a preferred embodiment the semi-transparent or transparent multi-dose container is a HDPE bottle.

[0003] EXAMPLE Hereinafter, the present invention will be explained in more detail below with reference to examples and comparative examples, while citing the 59ectoparasiticides formulation of the invention as preparation examples, and a stabilizing effect test as examination examples but the present invention is not restricted thereto. Material and Methods: The formulations tested are described in Table 1. The formulations were prepared by first preparing a 1 w / w% solution of FD&C Blue #1 in propylene glycol and a 1 w / w% solution of the additive compound (UV absorbing molecule BP-8 or Antioxidant BHT) in propylene glycol. Next Compound A (as disclosed before) was added to a small glass vial with a stir bar and then the appropriate amount of the stock solutions was added along with additional propylene glycol to reach the target concentrations of all components. Table 1: Formulations tested Control Inventive Comparative Component Function Formulation Example Example Wt.% Wt.% Wt.% Compound A API 0.96 0.96 0.96 FD&C Blue #1 Colorant 0.01 0.01 0.01 Anti- BHT 0 0 0.1 Oxidant UV BP-8 Absorbing 0 0.1 0 molecule Propylene Solvent q.s. q.s. q.s. Glycol Note: q.s. = amount sufficient to reach 100% The method used to test the photostability of the color and chemical stability is one cycle as described in ICH method Q1B using a Suntest CPS+ II chamber. The change of color of the test formulations was investigated by comparing images of test formulations before and after photo-exposure as shown in Figure 1. The color of the test formulations was further measured using a Hach Lange Colorimeter. The change in color was calculated using the formula: In which L*, a* and b* are the color parameters measured, each term is the difference between before exposure (i.e. exposure (i.e., total color change). The smaller the number the less the difference. Values less than two are not perceptible to the human eye and under 10 are still considered very similar colors. The results of these measurements are shown in Table 2. Table 2: Color change measurements Sample ΔE Control 40.7 Comparative Example 73.7 Inventive Example 5.1 Results: The control and comparative formulations show significant color change after photo-exposure, indicating instability, while the inventive formulation maintains its color, demonstrating the effectiveness of the UV absorbing molecule in stabilizing the color. The API (Compound A) content of the test formulations of Table before and after photo-exposure were characterized by liquid chromatography to determine both the degradation of the API and formation of photo-degradation products. Table 3 shows the results for these measurements. Table 3: API (Compound A) stability and photo-degradant formation API remaining after Photo- Major Photo Degradant exposure Level % Compared to Unexposed % Area Control 97.4 0.30 Inventive 101.5 0.02 Comparative 97.3 0.35 Results: These data show that incorporating a UV absorbing molecule in a pour-on formulation stabilizes the color of the formulation and reduces the degradation of the API. It was also shown that typical antioxidant additives alone, such as BHT, were not suitable to achieve such protective effect.

Claims

CLAIMS 1. A topical pour-on formulation, comprising a solvent and a compound of Formula (I)and N-oxides, veterinary acceptable acid addition salts, salt derivatives, solvates, ester derivatives, crystal polymorphs, isotopes, stereoisomers, and tautomers thereof, wherein A1 is CR5, N=O, or N; A2 is CR6, N=O, or N; A3is CR7, N=O, or N; A4is CR8, N=O or N; A5 is CR9, N=O or N ; wherein no more than 3 of A1, A2, A3, A4, A5are N or N=O; R1is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2;R2is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2and S-(Halo)5; R3is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2and S-(Halo)5; R4is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2 and S-(Halo)5 ; R5is selected from the group consisting of H, F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)Nhphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN,thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R6is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)Nhphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R7is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO,NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)Nhphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R8is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)Nhphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl,NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3- C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; R9is selected from the group consisting of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO2, OH, NH2, =O, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkylphenyl, (C1-C6)alkyl- S(O)2NH2, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkyl-S(O)2NH2, (C2- C6)alkenyl, (C2-C6)alkynyl, (C2-C6)haloalkenyl, (C3-C6)cycloalkenyl, (C3- C6)cycloalkyl, (C3-C6)halocycloalkenyl, (C3-C6)halocycloalkyl, (C1-C6)alkyl((C1- C6)alkyl)(=NO(C1-C6)alkyl), C(=NO(C1-C6)alkyl)(C1-C6)alkyl, C(=O)(C1-C6)alkyl, C(=O)NH(C1-C6)alkyl, C(=O)Nhphenyl, C(=O)O(C1-C6)alkyl, CH(=NO(C1-C6)alkyl), imidazolyl, N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)alkyl- O(C1-C6)alkyl), N((C1-C6)alkyl)(C(=O)(C1-C6)haloalkyl), N((C1-C6)alkyl)(C(=O)O(C1- C6)alkyl), N((C1-C6)alkyl)2, N(C(=O)O(C1-C6)alkyl)2, N=CH-phenyl, NH((C1- C6)alkylC(=O)(C1-C6)alkyl), NHC(=O)R10, N(C1-C6)alkyl-C(=O)lR10,NH(C1-C6)alkyl, NH(C1-C6)alkenyl, NH(C1-C6)alkynyl, NH(C1-C6)alkylphenyl, NH(S(O)2(C1-C6)alkyl), NH-C(=O)O(C1-C6)alkyl, oxazolyl, phenyl, pyrazolyl, pyridinyl, S(=NCN)((C1- C6)alkyl), S(C1-C6)alkyl, S(C1-C6)haloalkyl, S(O)(=NCN)((C1-C6)alkyl), S(O)(C1- C6)alkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, SCN, thiazolyl, thienyl, and triazolyl, wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl, alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl, halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl, pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, I, CN, OH, NH(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)alkyl, NH(C3-C6)cycloalkylCH2O(C1-C6)haloalkyl, NHCH2(C3-C6)cycloalkyl, NH2, NO2, oxo, (C1- C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, and C(=O)O-(C1-C6)alkyl; or R6and R7together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of -CH2-, -CH=, =CH-,-N=, =N-, -NH-, -O-, -S(O)-, -S(O)2- and -S-, wherein the ring formed by R6and R7is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, Cl, Br, I, CN, NO2, and =O; or R7and R8together with the atoms to which they are attached form a 5 or 6- atoms containing ring, wherein the ring-forming atoms are selected from the group consisting of -CH2-, -CH=, =CH-,-N=, =N-, -NH-, -O-, -S(O)-, -S(O)2- and - S-, wherein the ring formed by R7and R8is optionally substituted with one or more substituents of selected from the group consisting of (C1-C3)alkyl, F, Cl, Br, I, CN, NO2, and =O; R10is selected from the group consisting of H, (C1-C6)alkyl, C3-C6)cycloalkyl), (C1- C6)alkyloxy-(C1-C6)-alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1- C6)alkyloxy-(C1-C6)haloalkyl, C1-C6)alkyloxy-(C2-C6)-alkenyl, (C1-C6)alkyl-(C3- C6)cycloalkyl, heterocycle, aryl and (C1-C6)alkylphenyl; R11is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2; R12is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2; R13is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, CHO, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl,(C1-C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, (C1-C6)haloalkyl-S(O)2NH2, and triazolyl; R14is selected from the group consisting of H, F, Cl, Br, I, CN, NH2, NO2, (C1- C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C3-C6)cycloalkenyl, (C2-C6)alkynyl, (C1- C6)alkoxy, (C1-C6)haloalkyl, (C3-C6)halocycloalkyl, (C2-C6)haloalkenyl, (C3- C6)halocycloalkenyl, (C1-C6)haloalkoxy, S(C1-C6)alkyl, S(O)(C1-C6)alkyl, S(O)2(C1- C6)alkyl, S(C1-C6)haloalkyl, S(O)(C1-C6)haloalkyl, S(O)2(C1-C6)haloalkyl, (C1- C6)alkyl-S(O)2NH2, and (C1-C6)haloalkyl-S(O)2NH2; R15is selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2- C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)alkoxy(C1-C6)alkyl, C(=O)(C1-C6)alkyl, and (C1-C6)alkoxyC(=O)(C1-C6)alkyl H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl; wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I, characterized in that the formulation comprises a colorant and an UV absorbing molecule.

2. The topical pour-on formulation according to claim 1, wherein at least 1 of A1, A2, A3, A4, A5 is N, preferably 1 of A1, A2, A3, A4, A5 is N, preferably A1 or A2 is N.

3. The topical pour-on formulation according to any of the preceding claims, wherein at least two of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I, more preferably F or Cl.

4. The topical pour-on formulation according to any of the preceding claims, wherein R13is selected from the group consisting of H, F, Cl, CF3 and CH3,,preferably R13is Cl or F.

5. The topical pour-on formulation according to any of the preceding claims, wherein at least one of the following selections is made: R1is selected from the group consisting of H F, and Cl; and / or R2is selected from the group consisting of H, F, and Cl; and / or R3is selected from the group consisting of H, F, and Cl; and / R4is selected from the group consisting of H, F, and Cl.

6. The topical pour-on formulation according to any of the preceding claims, wherein at least one of the following selections is made: R5is selected from the group consisting of H F, Cl, Br, and I; and / or R6is selected from the group consisting of H, F, and Cl, Br, and CH3; and / or R7is selected from the group consisting of H F, Cl, Br, and I; and / or R8is selected from the group consisting of H, F, Cl, and Br, and CH3; and / or R9is selected from the group consisting of H F, Cl, Br, and I.

7. The topical pour-on formulation according to any of the preceding claims, wherein: R1is selected from the group consisting of H F, and Cl; R2is selected from the group consisting of H, F, and Cl; R3is selected from the group consisting of H, F, and Cl; R4is selected from the group consisting of H, F, and Cl; R5is selected from the group consisting of H F, Cl, Br, and I; R6is selected from the group consisting of H, F, and Cl, Br, and CH3; R7is selected from the group consisting of H F, Cl, Br, and I; R8is selected from the group consisting of H, F, Cl, and Br, and CH3; R9is selected from the group consisting of H F, Cl, Br, and I; R11is H;R12is selected from the group consisting of H, F, CL, CH3, CF3; R13is selected from the group consisting of H, F, Cl, CF3and CH3; R14is H or F; R15is selected from the group consisting of H and CH3; and wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I.

8. The topical pour-on formulation according to any of the preceding claims, wherein: R1is H; R2is selected from the group consisting of H, F, and Cl; R3is selected from the group consisting of H, Cl, F, and Br; R4is H, F, Cl; R5is selected from the group consisting of H F, and Cl; R6is selected from the group consisting of H, F, and Cl, and CH3; R7is selected from the group consisting of H F, and Cl; R8is selected from the group consisting of H, F, Cl, and CH3; R9is selected from the group consisting of H F, and Cl; R11is H; R12is selected from the group consisting of H, F and Cl; R13is selected from the group consisting of H, F, and Cl; R14is H; R15is selected from the group consisting of H and CH3; and wherein at least one of R5, R6, R7, R8, R9, is a substituent selected from the group consisting of F, Cl, Br, and I.

9. The topical pour-on formulation, wherein the compound of Formula (I) is F.

10. The topical pour-on formulation of any of the preceding claims, wherein the UV absorbing molecule is selected from the group consisting of a benzophenone compound, a cyanoacrylate compound, a benzotriazole compound and a salicylic acid compound.

11. The topical pour-on formulation of claim 10, wherein the UV absorbing molecule is a benzophenone compound, preferably dioxybenzone or oxybenzone, preferably dioxybenzone.

12. The topical pour-on formulation according to any of the preceding claims, wherein no other stabilizing compound is present in the formulation.

13. The topical pour-on formulation according to any of the preceding claims, wherein the colorant is Brilliant blue FCF (FD Blue #1).

14. The topical pour-on formulation according to any of the preceding claims, wherein the solvent is propylene glycol.

15. A veterinary product with the topical pour-on formulation according to any of the preceding claims in a semi-transparent or transparent multi-dose container.

16. The veterinary product of claim 15 wherein the multi-dose container is a HDPE bottle.

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