Title:
NITROOXYDERIVATIVE OF ROCK KINASE INHIBITOR
Document Type and Number:
WIPO Patent Application WO/2021/164351
Kind Code:
A1
Abstract:
The present invention provides a small molecular compound of a NO donor. The small molecular compound is characterized in that the small molecular compound is a compound represented by a structural formula I or a stereoisomer, a geometrical isomer, a tautomer, a racemate, a deuterated isotope derivative, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt, or a prodrug thereof; in the structural formula I, a ring A is a substituted or unsubstituted heteroaromatic ring; X is selected from (CH2)n, wherein n is selected from 0, 1, 2, and 3; R is a substituent of a terminal -O-NO2; R1 is selected from hydrogen, a hydroxyl group, halogen, an amino group, a cyano group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, and a substituted or unsubstituted heteroalkyl group; and R2 and R3 are respectively and independently selected from hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, and an amino protecting group, or R2 and R3 are connected to constitute a substituted or unsubstituted cyclic heteroalkyl group. The compound has a high-activity inhibition effect on ROCK kinase.
Inventors:
SHEN WANG (CN)
DANG KUIFENG (CN)
ZHANG CHAO (CN)
CHEN CHUNMING (CN)
SHAN LIHONG (CN)
DING WEN (CN)
WANG XIN (CN)
MI JIACHEN (CN)
SUN YABO (CN)
SHENG XIAXIN (CN)
SHEN JIALEI (CN)
LI YONG (CN)
DANG KUIFENG (CN)
ZHANG CHAO (CN)
CHEN CHUNMING (CN)
SHAN LIHONG (CN)
DING WEN (CN)
WANG XIN (CN)
MI JIACHEN (CN)
SUN YABO (CN)
SHENG XIAXIN (CN)
SHEN JIALEI (CN)
LI YONG (CN)
Application Number:
PCT/CN2020/129840
Publication Date:
August 26, 2021
Filing Date:
November 18, 2020
Export Citation:
Assignee:
VIVAVISION SHANGHAI LTD (CN)
International Classes:
C07D495/04; A61P27/06
Domestic Patent References:
| WO2018138293A1 | 2018-08-02 |
Foreign References:
| CN111217834A | 2020-06-02 | |||
| CN111606852A | 2020-09-01 |
Other References:
GUOYAN G. XU, TANVI M. DESHPANDE, MOHINI S. GHATGE, AKUL Y. MEHTA, ABDEL SATTAR M. OMAR, MOSTAFA H. AHMED, JURGEN VENITZ, OSHEIZA : "Design, Synthesis, and Investigation of Novel Nitric Oxide (NO)-Releasing Prodrugs as Drug Candidates for the Treatment of Ischemic Disorders: Insights into NO-Releasing Prodrug Biotransformation and Hemoglobin−NO Biochemistry", BIOCHEMISTRY, vol. 54, no. 49, 19 November 2015 (2015-11-19), pages 7178 - 7192, XP055387964, ISSN: 0006-2960, DOI: 10.1021/acs.biochem.5b01074
FEI YUE;ZHANG YIHUA;HUANG ZHANGJIAN: "Advance in Selective/Targeted Nitric Oxide Releasing Strategies", PROGRESS IN PHARMACEUTICAL SCIENCES, vol. 43, no. 11, 25 November 2019 (2019-11-25), pages 804 - 816, XP055838401, ISSN: 1001-5094
"Multifunctional kinases in cell behaviour", NAT. REV. MOL. CELL BIOL., no. 4, 2003, pages 446 - 456
"Involvement of Rho-kinase in hypertensive vascular disease: a novel therapeutic target in hypertension", FASEB J., vol. 15, no. 6, 2001, pages 1062 - 4
"Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension[J", NATURE, vol. 389, no. 6654, 1997, pages 990 - 4
"Isoform-specific targeting of ROCK proteins in immune cells", SMALL GTPASES, vol. 7, no. 3, 2016, pages 173 - 177
"Rho kinase inhibitors and their application to inflammatory disorders", CURR. TOP. MED. CHEM., no. 9, 2009, pages 704 - 723
"Antinociceptive effects of AS 1892802, a novel rho kinase inhibitor, in rat models of inflammatory and noninflammatory arthritis", J.PHARMACOL.EXP.THER., vol. 334, 2010, pages 955 - 963
"Administration of fasudil, a ROCK inhibitor, attenuates disease in lupus-prone NZB/W F1 female mice", LUPUS, vol. 21, no. 6, 2012, pages 656 - 61
"Therapeutic potential of experimental autoimmune encephalomyelitis by Fasudil, a Rho kinase inhibitor", J NEUROSCI RES, vol. 88, no. 8, 2010, pages 1664 - 72
"Role of Rho kinase signal pathway in inflammatory bowel disease", INT J CLINEXP MED, vol. 8, no. 3, 2015, pages 3089 - 3097
FEI YUE;ZHANG YIHUA;HUANG ZHANGJIAN: "Advance in Selective/Targeted Nitric Oxide Releasing Strategies", PROGRESS IN PHARMACEUTICAL SCIENCES, vol. 43, no. 11, 25 November 2019 (2019-11-25), pages 804 - 816, XP055838401, ISSN: 1001-5094
"Multifunctional kinases in cell behaviour", NAT. REV. MOL. CELL BIOL., no. 4, 2003, pages 446 - 456
"Involvement of Rho-kinase in hypertensive vascular disease: a novel therapeutic target in hypertension", FASEB J., vol. 15, no. 6, 2001, pages 1062 - 4
"Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension[J", NATURE, vol. 389, no. 6654, 1997, pages 990 - 4
"Isoform-specific targeting of ROCK proteins in immune cells", SMALL GTPASES, vol. 7, no. 3, 2016, pages 173 - 177
"Rho kinase inhibitors and their application to inflammatory disorders", CURR. TOP. MED. CHEM., no. 9, 2009, pages 704 - 723
"Antinociceptive effects of AS 1892802, a novel rho kinase inhibitor, in rat models of inflammatory and noninflammatory arthritis", J.PHARMACOL.EXP.THER., vol. 334, 2010, pages 955 - 963
"Administration of fasudil, a ROCK inhibitor, attenuates disease in lupus-prone NZB/W F1 female mice", LUPUS, vol. 21, no. 6, 2012, pages 656 - 61
"Therapeutic potential of experimental autoimmune encephalomyelitis by Fasudil, a Rho kinase inhibitor", J NEUROSCI RES, vol. 88, no. 8, 2010, pages 1664 - 72
"Role of Rho kinase signal pathway in inflammatory bowel disease", INT J CLINEXP MED, vol. 8, no. 3, 2015, pages 3089 - 3097
Attorney, Agent or Firm:
SHANGHAI CPTO INTELLECTUAL PROPERTY AGENCY CO. LTD (CN)
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