| US 7,615,568 B2 | ||
| Antithrombotic ethers | ||
| Jeffry Bernard Franciskovich, Zionsville, Ind. (US); David Kent Herron, Indianapolis, Ind. (US); Jared Harris Linebarger, Indianapolis, Ind. (US); Angela Lynn Marquart, Greenwood, Ind. (US); John Joseph Masters, Fishers, Ind. (US); David Mendel, Indianapolis, Ind. (US); Leander Merritt, Indianapolis, Ind. (US); Andrew Michael Ratz, Zionsville, Ind. (US); Gerald Floyd Smith, Greenwood, Ind. (US); Leland Otto Weigel, Indianpolis, Ind. (US); Michael Robert Wiley, Zionsville, Ind. (US); and Ying Kwong Yee, Carmel, Ind. (US) | ||
| Assigned to Eli Lilly and Company, Indianapolis, Ind. (US) | ||
| Appl. No. 10/556,313 PCT Filed Apr. 13, 2004, PCT No. PCT/US2004/009282 § 371(c)(1), (2), (4) Date Nov. 10, 2005, PCT Pub. No. WO2004/108677, PCT Pub. Date Dec. 10, 2004. |
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| Claims priority of provisional application 60/474689, filed on May 30, 2003. | ||
| Prior Publication US 2008/0108594 A1, May 08, 2008 | ||
| Int. Cl. A61K 31/4427 (2006.01); C07D 417/12 (2006.01) | ||
| U.S. Cl. 514—352 [546/270.7] | 16 Claims |
1. A compound of formula I,
 A3, A4, A5 and A6, together with the two carbons to which they are attached, complete a substituted pyridine ring in which
(a) A3 is N, and each of the others is CR4, CR5 or CR6, respectively; wherein R4 is hydrogen, carboxy, aminocarbonyl or methylaminocarbonyl; R5 is hydrogen, fluoro, chloro, or methyl; and R6 is hydrogen; or wherein each of R3, R4 and R6 is hydrogen and R5 is acetyl or cyano;
(b) A4 is N, and each of the others is CR3, CR5 or CR6, respectively; wherein each of R3 and R6 is hydrogen and R5 is hydrogen, methyl, acetyl or cyano;
(c) A5 is N, and each of the others is CR3, CR4 or CR6, respectively; wherein each of R3 and R6 is hydrogen and R4 is hydrogen, carboxy, aminocarbonyl or methylamino-carbonyl;
(d) A6 is N, and each of the others is CR3, CR4 or CR5, respectively; wherein R3 is hydrogen; R4 is hydrogen, carboxy, aminocarbonyl or methylaminocarbonyl; and R5 is hydrogen or methyl;
R is 2-pyridinyl (which may bear a methyl, cyano, carbamoyl, hydroxymethyl, formyl, vinyl, amino, hydroxy, methoxy, difluoromethoxy,
methylthio, fluoro or chloro substituent at the 5-position), or R is 3-pyridinyl (which may bear a methyl, fluoro or chloro
substituent at the 6-position), or R is phenyl (which may bear one, two or three substituents at the 3-, 4- or 5-position(s)
independently selected from fluoro, chloro, bromo, cyano, carbamoyl, methyl, methoxy, difluoromethoxy, hydroxymethyl, formyl,
vinyl, amino, hydroxy and 3,4-methylenedioxy; and in addition the phenyl may bear a 2-chloro or 2-fluoro substituent), or
R is 6-indolyl (which may bear a chloro or methyl substituent at the 3-position);
R1 is —(CH2)i-Q-(CH2)j—NRaRb in which
a) Q is a single bond; the sum of i and j is 2 or 3; and each of Ra and Rb is hydrogen, or each of Ra and Rb is independently (1-3C) normal alkyl, or Ra is hydrogen and Rb is (1-3C)alkyl or formyl, or NRaRb is 1-pyrrolidinyl or 4-morpholinyl;
b) Q is —CH(CH3)—, —C(CH3)2—, or —CH(ORc)—; each of i and j is 1; Ra is hydrogen; and Rb is hydrogen or methyl; and Rc is hydrogen, methyl or benzyl;
c) Q is cis- or trans-cyclohexane-1,4-diyl; each of i and j is 0; Ra is hydrogen; and Rb is hydrogen or methyl;
d) Q is —CHRd—; i is 0; j is 1; Ra is hydrogen or methyl; and Rb and Rd together are —(CH2)k— wherein k is 2 or 3;
e) Q is —CHRd—; i is 1; j is 1; Ra is hydrogen or methyl; and Rb and Rd together are —(CH2)k— wherein k is 1, 2 or 3; or
f) Q is —CHRd—; i is 0 or 1; j is 2; Ra is hydrogen or methyl; and Rb and Rd together are —(CH2)k— wherein k is 2; and
R2 is —(CH2)m—S(O)n—Re in which m is 0 or 1, n is 0, 1 or 2, and Re is (1-3C)alkyl or 2-fluoroethyl; and
wherein (1-3C) normal alkyl is methyl, ethyl or propyl; and (1-3C)alkyl is methyl, ethyl, propyl, or isopropyl.
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