Compound based on oxidative stress and anti-amyloid aggregation mechanism, preparation method therefor and use thereof

{
  "publication_number": "US2026103485A1",
  "country": "US",
  "kind": "A1",
  "title": "Compound based on oxidative stress and anti-amyloid aggregation mechanism, preparation method therefor and use thereof",
  "abstract": "The present invention relates to a compound based on oxidative stress and anti-amyloid aggregation mechanism, a preparation method therefor, and a use thereof. The compound of the present invention has a structure represented by formula (I) or formula (II), can change biomechanical characteristics of a lens to ameliorate age-related lens component changes as well as presbyopia and cataract caused thereby, and therefore can treat age-related presbyopia and cataract diseases and produce a synergistic effect.",
  "claims": [
    "1. A compound represented by formula (I) or (II), or a pharmaceutically acceptable salt or isomer thereof: wherein, R 1 is selected from the group consisting of OH, NH 2, and or R 1 is selected from the group consisting of C 1-6 alkyl, - OC 1-6 alkyl, - OC(═O)C 1-6 alkyl, C 1-6 heteroalkyl, - OC 1-6 heteroalkyl, - OC(═O)C 1-6 heteroalkyl, C 3-8 cycloalkyl, - OC 3-8 cycloalkyl, - OC(═O)C 3-8 cycloalkyl, 5-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl, which are unsubstituted or substituted by 1, 2 or 3 Rs; R 2 is selected from the group consisting of H, F, Cl, Br, I, NH 2, OH, COOH, and CONH 2; R 3 is selected from the group consisting of H, F, Cl, Br, I, NH 2, and OH, or R 3 is selected from the group consisting of C 1-6 alkyl unsubstituted or substituted by 1, 2 or 3 Rs; the “ ” between carbon atoms No. 3 and 7 is a single or double bond, and when it is a single bond, R 4 is H; and when it is a double bond, R 4 is absent; the “ ” between adjacent carbon atoms No. 8, 9 and 10 is a single or double bond, and the two bonds cannot be double bonds simultaneously; R 5 is independently selected from the group consisting of H, and C 1-6 alkyl unsubstituted or substituted by 1, 2 or 3 Rs; the “ ” between carbon atoms No. 21 and 22 is a single or double bond, and when it is a single bond, R 6 is selected from the group consisting of OH, NH 2, and or R 6 is selected from the group consisting of C 1-6 alkyl, - OC 1-6 alkyl, - OC(═O)C 1-6 alkyl, C 1-6 heteroalkyl, - OC 1-6 heteroalkyl, - OC(═O)C 1-6 heteroalkyl, C 3-8 cycloalkyl, - OC 3-8 cycloalkyl, - OC(═O)C 3-8 cycloalkyl, 5-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl, which are unsubstituted or substituted by 1, 2 or 3 Rs; and when it is a double bond, R 6 is absent; R 7 is selected from the group consisting of C 1-12 alkyl and C 1-12 heteroalkyl, which are unsubstituted or substituted by 1, 2, or 3 Rs; R 8 is selected from the group consisting of C 1-12 alkyl and C 1-12 heteroalkyl, which are unsubstituted or substituted by 1, 2, 3, or 4 Rs; Rs are independently selected from the group consisting of F, Cl, Br, I, NH 2, OH, COOH, CONH 2, C16 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl; the “hetero” in the heteroalkyl, heterocycloalkyl, and heteroaryl is independently selected from the following heteroatoms or heteroradicals: - NH -, N, - O -, and - S -; and the number of the heteroatom or heteroradical is independently selected from 1, 2, and 3. 2. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein Rs are each independently selected from the group consisting of F, Cl, Br, I, NH 2, OH, COOH, CONH 2, CH 3, - CH 2 CH 3, - (CH 2) 2 CH 3, - (CH 2) 3 CH 3, - CH═CH 2, and - CH═CH - CH 2. 3. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 1 is selected from the group consisting of OH, NH 2, and or R 1 is selected from the group consisting of unsubstituted or substituted by 1, 2, or 3 Rs, wherein, R 7 is selected from the group consisting of C 1-6 alkyl and - NH - C 1-6 alkyl-, which are unsubstituted or substituted by 1, 2, or 3 Rs; R 8 is selected from the group consisting of C 1-6 alkyl and - C 1-6 alkyl-NH 2, which are unsubstituted or substituted by 1, 2, 3, or 4 Rs. 4. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 1 is selected from the group consisting of OH, NH 2, and wherein, R 7 and R 7 ′ are each independently selected from the group consisting of C 1-6 alkyl unsubstituted or substituted by 1, 2, or 3 Rs, preferably methyl, ethyl and propyl, which are unsubstituted or substituted by 1, 2, or 3 Rs. 5. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 1 is selected from the group consisting of: 6. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 2 is selected from the group consisting of H, F, Cl, NH 2, OH, COOH, and CONH 2. 7. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 3 is selected from the group consisting of H, F, Cl, Br, I, NH 2, OH, CH 3, - CH 2 OH, - CH 2 CH 3, - (CH 2) 2 OH, and - (CH 2) 3 CH 3. 8. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein Rs is selected from the group consisting of H, CH 3, - CH 2 OH, - CH 2 CH 3, and - (CH 2) 2 OH. 9. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 6 is selected from the group consisting of OH, NH 2, and or R 6 is selected from the group consisting of unsubstituted or substituted by 1, 2, or 3 Rs, wherein, R 7 is selected from the group consisting of C 1-6 alkyl and - NH - C 1-6 alkyl-, which are unsubstituted or substituted by 1, 2, or 3 Rs; R 8 is selected from C 1-6 alkyl and - C 1-6 alkyl-NH 2, which are unsubstituted or substituted by 1, 2, 3, or 4 Rs. 10. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 6 is selected from the group consisting of OH, NH 2, and wherein, R 7 and R 7 ′ are independently selected from the group consisting of C 1-6 alkyl unsubstituted or substituted by 1, 2, or 3 Rs. 11. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 6 is selected from the group consisting of: 12. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein R 7 and R 7 ′ are independently selected from the group consisting of - CH 2 -, - (CH 2) 2 -, - CH 2 CH(CH 3) -, - (CH 2) 3 -, - CH 2 NH -, and - (CH 2) 2 NH -. 13. The compound according to claim 1, or a pharmaceutically acceptable salt or isomer thereof, wherein Rs is selected from the group consisting of - CH 2 CH 3, - (CH 2) 2 CH 3, - CH 2 COOH, - (CH 2) 2 COOH, - (CH 2) 3 COOH, - CH 2 CH(CH 3) COOH, and - CH(CH 3) CH 2 COOH. 14. A compound of the following formulae, or a pharmaceutically acceptable salt or isomer thereof: 15. A pharmaceutical composition comprising a therapeutically effective amount of the compound or the pharmaceutically acceptable salt or isomer thereof according to claim 1. 16. A method for treating an ophthalmic disease, comprising a step of administering a therapeutically effective amount of the compound or the pharmaceutically acceptable salt or isomer thereof according to claim 1, to a subject. 17. The method according to claim 16, wherein the ophthalmic disease for includes cataracts and/or presbyopia. 18. The method according to claim 17, wherein the compound, or the pharmaceutically acceptable salt or isomer thereof is administered via the eyes. 19. A method for preparing the compound or the pharmaceutically acceptable salt or isomer thereof according to claim 1, wherein the method is at least one selected from the following schemes: wherein, Xa represents a leaving group, for example, it is selected from the group consisting of hydroxyl and chlorine."
  ],
  "description_excerpt": "The present invention belongs to the field of biomedicine technology, and specifically relates to a compound based on oxidative stress and anti-amyloid aggregation mechanism, and a preparation method and use thereof.\n\nThe lens of the eye is located in front of the vitreous body and connected to the ciliary body by the circumferential suspensory ligaments of the lens, and is biconvex and flexible. The lens is a biconvex transparent tissue fixed by the suspensory ligaments and suspended behind the iris and in front of the vitreous body. The lens is an important part of the eye's dioptric system and the only refractive medium with accommodation ability. The accommodation ability gradually decreases with age, resulting in presbyopia.\n\nAge-related changes in lens components include changes in oxidative stress, such as an increase in the proportion of protein disulfide bonds, and an increase in amyloid-insoluble proteins (LIAO Xuan, LAN Changjun, Thiol transferase and lens redox regulation [J]. Journal of North Sichuan Medical College, 2011, 26(2): 190-193.; Rich W, Reilly M A. A Review of Lens Biomechanical Contributions to Presbyopia[J]. Current Eye Research, 2022:1-13.). The molecular mechanisms of presbyopia (old eyes) and age-related cataracts are both related to oxidative stress and amyloid-insoluble proteins. (Truscott R J. Presbyopia. Emerging from a blur towards an understanding of the molecular basis for this most common eye condition[J]. Experimental eye research, 2009, 88(2): 241-247.; Rocha K M. Presbyopia on the Horizon[J]. Journal of Refractive Surgery, 2021, 37(S1): S6-S7.; Ho M C, Peng Y J, Chen S J, et al.",
  "cpc": [
    "C07J 31/006",
    "A61K 31/575",
    "C07J 41/0088"
  ],
  "assignees": [
    "Shenzhen Raytone Pharmaceutical Co Ltd"
  ],
  "inventors": [
    "Yanbo LING",
    "Jialin XING",
    "Jiamin CUI",
    "Boyang JING",
    "Zhenhua Zhang",
    "Chao He"
  ],
  "filing_date": "2022-12-29",
  "publication_date": "2026-04-16",
  "priority_date": "2022-10-14",
  "application_number": "US-202219112294-A",
  "cited_by_count": 0
}