Reference

Preparation of azolidinone-vinyl fused-benzene derivatives for therapeutic uses as PI3 kinase inhibitors

Preparation of azolidinone-vinyl fused-benzene derivatives for therapeutic uses as PI3 kinase inhibitors. Rueckle, Thomas; Jiang, Xuliang; Gaillard, Pascale; Church, Dennis; Vallotton, Tania (Applied Research Systems Ars Holding N.V., Neth. Antilles). PCT Int. Appl. WO 2004007491 A1 22 Jan 2004, 142 pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NI, NO, NZ, OM, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR.Some commonly used reagents like 648450-22-0 and 43041-12-9 are used in this experiment. (English). (World Intellectual Property Organization). CODEN: PIXXD2. CLASS: ICM: C07D417-06. ICS: C07D277-18; A61K031-00; A61P037-06. APPLICATION: WO 2003-EP50302 10 Jul 2003. PRIORITY: EP 2002-100798 10 Jul 2002; US 2002-289998 7 Nov 2002. DOCUMENT TYPE: Patent CA Section: 28 (Heterocyclic Compounds (More Than One Hetero Atom)) Section cross-reference(s): 1, 63 The present invention is related to the prepn. of azolidinedione-vinyl fused-benzene derivs., such as I [R1 = H, CN, carboxy, acyl, alkoxy, halogen, acyloxy, etc.; A = fused heterocyclic or carbocyclic ring; Y1, Y2 = S, O, NH], and their use in pharmaceutical compns. as PI3 kinase (PI3K) inhibitors. These azolidinones are claimed for use in the treatment and/or prophylaxis of autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, cancer, graft rejection, lung injuries, chronic obstructive pulmonary disease, anaphylactic shock, fibrosis, psoriasis, allergic diseases, asthma, stroke or ischemic conditions, ischemia-reperfusion, platelet aggregation/activation, skeletal muscle atrophy/hypertrophy, leukocyte recruitment in cancer tissue, angiogenesis, invasion metastasis in melanoma and Kaposi's sarcoma, sepsis, transplantation, pancreatitis, multi-organ failure, glomerulosclerosis, glomerulonephritis, progressive renal fibrosis, endothelial and epithelial injuries in the lung or in general lung airways inflammation. Further, these azolidinones are claimed for use in the treatment of atherosclerosis, hypertrophy, cardiac myocyte dysfunction, elevated blood pressure, vasoconstriction, Alzheimer's disease, Huntington's disease, CNS trauma, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, thrombosis, and brain infection/inflammation such as meningitis or encephalitis. Thus, azolidinone II was prepd. via a condensation reaction of piperonal with 2,4-thiazolidinedione using b-alanine in acetic acid and stirring at 100° for 3 h. Some of the prepd. azolidinones were assayed for PI3Kg inhibition using a high throughput PI3K lipid kinase binding assay. Tablet, capsule, liq. and injectable pharmaceutical compns. were presented. .

Preparation of dioxothiazolylidenemethyl derivatives for increasing spermatozoa motility

Preparation of dioxothiazolylidenemethyl derivatives for increasing spermatozoa motility. De Luca, Giampiero (Applied Research Systems Ars Holding NV, Neth. Antilles). PCT Int. Appl. WO 2004006916 A1 22 Jan 2004, 131 pp.Some commonly used reagents like 648449-77-8 and 648450-69-5 are used in this experiment. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization). CODEN: PIXXD2. CLASS: ICM: A61K031-426. ICS: A61K031-423; A61K031-428; A61K031-538; A61K031-4166; A61K031-4168; A61K031-422; A01N001-02. APPLICATION: WO 2003-EP50303 10 Jul 2003. PRIORITY: EP 2002-100799 10 Jul 2002; EP 2002-102876 23 Dec 2002. DOCUMENT TYPE: Patent CA Section: 28 (Heterocyclic Compounds (More Than One Hetero Atom)) Section cross-reference(s): 1, 63 Title compds. I [X = S, O, NH; Y1-2 = S, O, NH; Cy = 5-8 membered, optionally fused, carbo/heterocyclic ring] are prepd. For instance, thiazolidine-2,4-dione is condensed with piperonal (HOAc, b-alanine, 3 h, 100°) to give II. Selected examples have IC50 < 1 mM for the phosphatidylinositol-3-kinase (PI3Kg) receptor. I are useful for the improvement of spermatozoa fertilization activity; in particular for the increase of spermatozoa motility. Furthermore, I are used to treat infertility and assisted reprodn. techniques (ART). .