摘要:
The present invention is an improved process for the preparation of a sodium/proton exchange inhibitor of sub-type 3 (NHE-3) useful in the treatment of sleep apnea and other related respiratory disorders. The improved synthesis of the NHE-3 inhibitor, more specifically a benzimidazol thienylamine, utilizes novel reagents and chemical intermediates and thereby results in an improved yield and purity of the final product with less reaction or synthetic steps required
摘要:
The present invention is directed to a method for the preparation of 2,2,2-trifluoro-n-(4-fluoro-3-pyridin-4-yl-benzyl)-acetamide hydrochloride of the formula: and reaction intermediates used in the method.
摘要:
The present invention is directed to an indole benzylamine compound of formula I: useful as an inhibitor of tryptase. In addition, the present invention is directed to the use of the compound for treating a patient suffering from, or subject to, a physiological condition in need of amelioration by inhibition of tryptase, comprising administering to the patient of a therapeutically effective amount of the compound, and to a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula I, and a pharmaceutically acceptable carrier.
摘要:
The present invention is an improved method for the preparation of (4-fluoro-3-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester, compound of formula I. The invention is directed to a method of synthesis for the compound of formula I in three steps, comprising formation of 5-((tert-butoxycarbonyl)aminomethyl)-2-fluorobenzeneboronic acid (compound 11), reaction of compound 11 under Suzuki coupling conditions to yield (4-fluoro-2-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester and selective hydrogenation of the aforementioned product under hydrogenation conditions yields compound I. The invention is also directed to the intermediates 5-((tert-butoxycarbonyl)amino-methyl)-2-fluorobenzeneboronic acid (compound 11), and (4-fluoro-3-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester (compound 13).
摘要:
Cis-epoxide compounds of formula (I-1) and pharmaceutically acceptable salts, hydrates and solvates thereof: ##STR1## wherein: R.sup.1 is a cycloalkyl, or aryl-substituted lower alkyl group; A is a functionalized acyl group of the formula ##STR2## wherein R.sup.2 is a C.sub.1-4 alkyl, or amide-substituted C.sub.1-2 alkyl group; R.sup.3 is a C.sub.1-4 alkoxy, aryloxyalkyl or arylalkoxy, or a nitrogen-containing aromatic radical, or a lower alkoxy group substituted with a nitrogen-containing aromatic radical, or a radical having the formula of ##STR3## wherein R.sup.4 is a hydrogen or a methyl group and R.sup.5 is an alkyl group substituted with a nitrogen-containing aromatic radical; and m is 0 or 1; and B is a functionalized amino group of the formula ##STR4## wherein R.sup.8 and R.sup.9 are independently a C.sub.1-4 alkyl group optionally substituted with an aromatic radical, or an aromatic group.
摘要:
Cis-epoxide compounds of formula (I-3) and pharmaceutically acceptable salts, hydrates and solvates thereof: ##STR1## wherein: R.sup.1 is a cycloalkyl, or arly-substituted lower alkyl group; K and J are independently a group having the formula of ##STR2## wherein R.sup.18 is a lower alkyl group optionally substituted with an aryl radical; X is O, NH, or N--CH.sub.3 ; and R.sup.19 is an aromatic hetercyclic sysstem containing a nitrogen atom in its ring, or a lower alkyl group optionally substituted with an aryl radical, or a hydrogen; G is an amino acid which is linked to K-- and ##STR3## by peptide bonds in formula (I-3); Q is an amino acid which is linked to by peptide bonds in formula (I-3), or a group having the formula of wherein R.sup.20 is a lower alkyl group optionally substituted with an aromatic radical; and Y is CH.sub.2, O or NH; and r is 0 or 1, except that Q is a group having the formula of r is 0.
摘要:
Novel cis-epoxide compounds of formula (I) are useful for treating or preventing diseases caused by HIV infection: ##STR1## wherein A, B, R.sub.1 to R.sub.4 and n have the same meanings as defined in the specification. The novel HIV protease inhibitor of the formula (I) has a specific structure to form a stable bonding with the enzyme active site, which entails a highly enhanced irreversible inhibition against HIV protease.
摘要:
The present invention relates to novel compounds of formula (I) which has inhibitory activities against human immunodeficiency virus ("HIV") protease, a process for the preparation thereof, and compositions for prevention or treatment of AIDS by HIV infection comprising the above compounds as active ingredients. ##STR1## wherein: R.sup.1 is an aromatic group, a nitrogen-containing aromatic group, C.sub.1-4 alkyl group optionally substituted with an aromatic group or a nitrogen-containing aromatic group, C.sub.1-4 alkoxy group optionally substituted with an aromatic group or a nitrogen-containing aromatic group; R.sup.2 is an amino acid residue or a C.sub.1-8 alkyl group substituted with a C.sub.1-4 alkylsulfonyl group; R.sup.3 is a C.sub.1-4 alkyl group optionally substituted with an aromatic group; R.sup.4 is hydrogen or a C.sub.1-2 alkyl group; R.sup.5 is a C.sub.1-10 alkyl group optionally substituted with an aromatic group; and n is 1 or 2.
摘要:
A compound of the following structure: wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, —CH2CH(CH3)—, —CH═CH—, —CH═C(CH3)—, or —C≡C—; R4 is (CH2)p where p is an integer in the range of 4 to 12, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5C(Rs1)═C(Rs2)C(Rs3)═C(Rs4)—, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rs1)CH(Rs2)C(Rs3)═C(Rs4)—, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5C(Rs1)═C(Rs2)CH(Rs3)CH(Rs4)—, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rs1)CH(Rs2)CH(Rs3)CH(Rs4)—, wherein y1 and y2 are 1 and y3, y4 and y5 are independently 0 or 1, Rk1, Rk2, Rk3, Rk4 and Rk5 are independently H, CH3, or OR2a, and Rs1, Rs2, Rs3, and Rs4 are independently H or CH3, wherein R2a is H, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; and R5 is H or OR2b, wherein R2b is H, an alkyl group, an aryl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.
摘要:
A compound of the following structure: wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, —CH2CH(CH3)—, —CH═CH—, —CH═C(CH3)—, or —C≡C—; R4 is (CH2)p where p is an integer in the range of 4 to 12, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5C(Rs1)═C(Rs2)C(Rs3)═C(Rs4)—, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rs1) CH(Rs2)C(Rs3)═C(Rs4)—, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5C(Rs1)═C(Rs2)CH(Rs3)CH(Rs4)—, —(CHRk1)y1(CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rs1) CH(Rs2)CH(Rs3)CH(Rs4)—, wherein y1 and y2 are 1 and y3, y4 and y5 are independently 0 or 1, Rk1, Rk2, Rk3, Rk4 and Rk5 are independently H, CH3, or OR2a, and Rs1, Rs2, Rs3, and Rs4 are independently H or CH3, wherein R2a is H, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; and R5 is H or OR2b, wherein R2b is H, an alkyl group, an aryl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.