Search criteria:
List of files deposited in CurateND that match your search criteria
-
- Inventor(s):
- Marvin J. Miller
- Patent Number:
- US 4820815 B2
- Description:
The invention provides azetidinones of the formula ##STR1## where R.sub.4 is hydrogen, amino or protected amino; R.sup.0 is H when R.sub.4 is amino or protected amino, or C.sub.1 -C.sub.4 alkyl when R.sub.4 is H; R.sub.1 is H, CH.sub.3, –CH.sub.2 –.sub.n Y where Y is OH, protected OH, –CH.sub.2 OH, protected –CH.sub.2 OH, halogen, COOH or protected COOH; n is 1 or 2; –CH.sub.2 –C(O)SR.sub.1 ‘ where R.sub.1 ’ is e.g., C.sub.1 -C.sub.4 alkyl; R.sub.2 is H or protecting group and R…
- Date Issued:
- 1989-04-11
- Record Visibility:
- Public
- Title
- Azetidinone N-phosphonomethyl esters
- Description
- The invention provides azetidinones of the formula ##STR1## where R.sub.4 is hydrogen, amino or protected amino; R.sup.0 is H when R.sub.4 is amino or protected amino, or C.sub.1 -C.sub.4 alkyl when R.sub.4 is H; R.sub.1 is H, CH.sub.3, --CH.sub.2 --.sub.n Y where Y is OH, protected OH, --CH.sub.2 OH, protected --CH.sub.2 OH, halogen, COOH or protected COOH; n is 1 or 2; --CH.sub.2 --C(O)SR.sub.1 ' where R.sub.1 ' is e.g., C.sub.1 -C.sub.4 alkyl; R.sub.2 is H or protecting group and R.sub.3 is e.g., alkyl or phenyl. The azetidinones obtained are useful intermediates to carbapenems and carbacephems and monocyclic antibacterials, e.g., .alpha.-(dialkylphosphono)-[[3.beta.-[2-(2-aminothiazol-4-yl)-2-(syn)metho xyiminoacetylamino]azetidin-2-one-1-yl]]acetic acid and pharmaceutically acceptable salts thereof.
- Creator
- Marvin J. Miller
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Chi-Nung W. Hsiao, Marvin J. Miller
- Patent Number:
- US 4845229 B2
- Description:
A stereoselective process for chiral intermediates to 1-carbapenem and 1-carbacephalosporins is provided comprising the use of an N-acyl-(4R)-substituted-1,3-thiazolidine-2-thione as a chiral auxiliary in boron enolate mediated aldol condensation with a protected-.beta.-keto ester aldehyde. E.g., benzyl 3,3-(ethylenedioxy)-4-formylbutyrate is condensed with the boron enolate formed with n-butyryl (4R)-methoxycarbonyl-1,3-thiazolidine-2-thione to provide benzyl 3,3-ethylenedioxy-(5R)-hydroxy-6…
- Date Issued:
- 1989-07-04
- Record Visibility:
- Public
- Title
- Process for intermediates to 1-carbapenems and 1-carbacephems
- Description
- A stereoselective process for chiral intermediates to 1-carbapenem and 1-carbacephalosporins is provided comprising the use of an N-acyl-(4R)-substituted-1,3-thiazolidine-2-thione as a chiral auxiliary in boron enolate mediated aldol condensation with a protected-.beta.-keto ester aldehyde. E.g., benzyl 3,3-(ethylenedioxy)-4-formylbutyrate is condensed with the boron enolate formed with n-butyryl (4R)-methoxycarbonyl-1,3-thiazolidine-2-thione to provide benzyl 3,3-ethylenedioxy-(5R)-hydroxy-6-[(4R)-methoxycarbonyl-1,3-thiazolidine-2- thione-3-ylcarbonyl]octanoate. Displacement of the thiazolidine-2-thione chiral auxiliary moiety with an O-alkyl, O-acyl or O-aralkyl hydroxyamine provides the corresponding chiral intermediate as the hydroxamate.
- Creator
- Chi-Nung W. Hsiao, Marvin J. Miller
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller, Jingdan Hu
- Patent Number:
- US 6403623 B2
- Description:
Method for treating tuberculosis with 2-(2-substituted-phenyl)-2-oxazolines and related 5-membered heterocycles represented by the formula ##STR1## Y.sub.1 is e.g. an ester or amide forming group, and X is O, S, or NH; and pharmaceutically acceptable formulations useful therein are provided. A preferred method comprises administering (S)-benzyl2-[2-(benzyloxy)phenyl]-2-oxazoline-4-carboxylate in a suitable formulation. The compounds of the above formula are prepared by known methods, e.g. the…
- Date Issued:
- 2002-06-11
- Record Visibility:
- Public
- Title
- Heterocyclic antituberculosis agents
- Description
- Method for treating tuberculosis with 2-(2-substituted-phenyl)-2-oxazolines and related 5-membered heterocycles represented by the formula ##STR1## Y.sub.1 is e.g. an ester or amide forming group, and X is O, S, or NH; and pharmaceutically acceptable formulations useful therein are provided. A preferred method comprises administering (S)-benzyl2-[2-(benzyloxy)phenyl]-2-oxazoline-4-carboxylate in a suitable formulation. The compounds of the above formula are prepared by known methods, e.g. the oxazolines are obtained by coupling a substituted benzoic acid with a serine ester or threonine ester and cyclizing the coupled product.
- Creator
- Marvin J. Miller, Jingdan Hu
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Min Teng, Marvin J. Miller
- Patent Number:
- US 5750681 B2
- Description:
Bicyclic .beta.-lactams comprising a 5- or 6-membered lactone or lactam ring are obtained in a process comprising a base induced intramolecular cyclization of a 4-substututed .beta.-lactam having a leaving group in the 1-position. An intramolecular nucleophile transfer reaction is proposed as the operative mechanism and the bicyclic .beta.-lactams are obtained in the required stereochemical form for biological activity. The compounds provided are useful intermediates for the preparation of an…
- Date Issued:
- 1998-05-12
- Record Visibility:
- Public
- Title
- Bicyclic beta-lactams and process therefor
- Description
- Bicyclic .beta.-lactams comprising a 5- or 6-membered lactone or lactam ring are obtained in a process comprising a base induced intramolecular cyclization of a 4-substututed .beta.-lactam having a leaving group in the 1-position. An intramolecular nucleophile transfer reaction is proposed as the operative mechanism and the bicyclic .beta.-lactams are obtained in the required stereochemical form for biological activity. The compounds provided are useful intermediates for the preparation of antibiotics and .beta.-lactamase inhibitors.
- Creator
- Min Teng, Marvin J. Miller
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller
- Patent Number:
- US 4595532 B2
- Description:
N-Mono or N-disubstituted methyl-2-azetidinones are provided via cyclization of .beta.-hydroxy or .beta.-halo substituted acid sec-amides wherein the amide nitrogen is substituted with a mono- or di-substituted methyl group having activating substituents. Cyclization of .beta.-hydroxy acid amides is mediated by triphenylphosphine-dialkylazodicarboxylate while cyclization of .beta.-halo acid amides is mediated by strong bases e.g. lithium dialkylamides. E.g. Diethyl amino-protected L-serylamin…
- Date Issued:
- 1986-06-17
- Record Visibility:
- Public
- Title
- N-(substituted-methyl)-azetidin-2-ones
- Description
- N-Mono or N-disubstituted methyl-2-azetidinones are provided via cyclization of .beta.-hydroxy or .beta.-halo substituted acid sec-amides wherein the amide nitrogen is substituted with a mono- or di-substituted methyl group having activating substituents. Cyclization of .beta.-hydroxy acid amides is mediated by triphenylphosphine-dialkylazodicarboxylate while cyclization of .beta.-halo acid amides is mediated by strong bases e.g. lithium dialkylamides. E.g. Diethyl amino-protected L-serylaminomalonate is cyclized with 200 mole % TPP-diisopropylazodicarboxylate to N-(diethoxycarbonylmethyl)-3-protected-amino-2-azetidinone. The 2-azetidinones provided are useful intermediates.
- Creator
- Marvin J. Miller
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller
- Patent Number:
- US 4675399 B2
- Description:
Process for N-acyloxy or sulfooxy 2-azetidinones comprising O-acylation of a .beta.-hydroxy or .beta.-halo hydroxamic acid, and cyclizing the O-acylhydroxamate with TPP-CCl.sub.4 -TEA or with TPP-dialkylazodicarboxylate to the N-acyloxy-2-azetidinone. Solvolysis of the acyl group provides an N-hydroxy-2-azetidinone. e.g., N-Cbz-L-serine is converted to the O-acetyl hydroxamate, cyclized and solvolyzed to N-hydroxy-3-(Cbz-amino)-2-azetidinone. The N-hydroxy-2-azetidinones are useful intermedia…
- Date Issued:
- 1987-06-23
- Record Visibility:
- Public
- Title
- Cyclization process for .beta.-lactams
- Description
- Process for N-acyloxy or sulfooxy 2-azetidinones comprising O-acylation of a .beta.-hydroxy or .beta.-halo hydroxamic acid, and cyclizing the O-acylhydroxamate with TPP-CCl.sub.4 -TEA or with TPP-dialkylazodicarboxylate to the N-acyloxy-2-azetidinone. Solvolysis of the acyl group provides an N-hydroxy-2-azetidinone. e.g., N-Cbz-L-serine is converted to the O-acetyl hydroxamate, cyclized and solvolyzed to N-hydroxy-3-(Cbz-amino)-2-azetidinone. The N-hydroxy-2-azetidinones are useful intermediates to monocyclic .beta.-lactam antibiotics and .beta.-lactamase inhibitors.
- Creator
- Marvin J. Miller
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller
- Patent Number:
- US 5266468 B2
- Description:
.beta.-Hydroxy-.alpha.-amino acids are obtained via serine hydroxymethyltransferase catalyzed condensation of aldehydes with glycine. The predominant product with most aldehydes is the L-erythro diastereomer. For example, succinic semialdehyde methylester is condensed with glycine in the process to provide L-erythro .alpha.-amino hydroxy adipic acid mono methyl ester.
- Date Issued:
- 1993-11-30
- Record Visibility:
- Public
- Title
- Process for preparing .beta.-hydroxy-.alpha. amino acids
- Description
- .beta.-Hydroxy-.alpha.-amino acids are obtained via serine hydroxymethyltransferase catalyzed condensation of aldehydes with glycine. The predominant product with most aldehydes is the L-erythro diastereomer. For example, succinic semialdehyde methylester is condensed with glycine in the process to provide L-erythro .alpha.-amino hydroxy adipic acid mono methyl ester.
- Creator
- Marvin J. Miller
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Catherine M. Gasparski, Marvin J. Miller, Min Teng
- Patent Number:
- US 5250676 B2
- Description:
Provided is a process for diastereoselectively preparing compounds of the formula ##STR1## which includes the step of subjecting a compound of the formula ##STR2## to a salt whose anion is a nucleophilic base whose conjugate acid has a pKa in the range of between about -7 to about 14, or a silylated derivative of the salt; wherein R.sub.1 is said nucleophile; R is hydrogen, or protected amino, R.sub.2 is R.sub.4 as defined herein below; R.sub.3 is a leaving group; and R.sub.4 is hydrogen, C.s…
- Date Issued:
- 1993-10-05
- Record Visibility:
- Public
- Title
- Process for the preparation of 3-substituted-2-azetidinones
- Description
- Provided is a process for diastereoselectively preparing compounds of the formula ##STR1## which includes the step of subjecting a compound of the formula ##STR2## to a salt whose anion is a nucleophilic base whose conjugate acid has a pKa in the range of between about -7 to about 14, or a silylated derivative of the salt; wherein R.sub.1 is said nucleophile; R is hydrogen, or protected amino, R.sub.2 is R.sub.4 as defined herein below; R.sub.3 is a leaving group; and R.sub.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or a group of the formula wherein R.sub.6 is 2-furyl, naphthyl, phenyl, phenyl substituted with 1, 2 or 3 substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, nitro, halo, carboxy and amido; or R.sub.6 is a group of the formula in which R.sub.7 is selected from C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, benzyl, phenyl, or benzyl or phenyl substituted with 1, 2 or 3 substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, nitro, halo, carboxy and amido; or R.sub.4 is a group of the formula ##STR3## wherein L is --OR.sub.7 where R.sub.7 is as defined; or R.sub.4 is a group of the formula ##STR4## wherein: G is trimethylsilylmethyl, hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 substituted alkyl, phenyl, or phenyl substituted with 1, 2 or 3 substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, nitro, halo, carboxy and amido.
- Creator
- Catherine M. Gasparski, Marvin J. Miller, Min Teng
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller, Matthew A. Williams
- Patent Number:
- US 5106968 B2
- Description:
1-Carbapenam-2-one-3-carboxylic acid and 1-carba-3-hydroxy-3-cephem-4-carboxylic acid and esters thereof are provided by a process comprising a rhodium C.sub.2 -C.sub.10 carboxylate catalyzed cyclization of an ester of a 4-(1-alkoxy- or 1-substituted alkoxy)-2-oxo-4-azetidinyl)-.beta.-ketobutyric acid and an ester of a 5-(1-alkoxy- or 1-substituted alkoxy-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketovaleric acid respectively. The process is carried out in an inert organic solvent at a tempera…
- Date Issued:
- 1992-04-21
- Record Visibility:
- Public
- Title
- Process for bicyclic .beta.-lactams diazo-.beta.-keto-butyrate-intermediates for bicyclic .beta.-lactams
- Description
- 1-Carbapenam-2-one-3-carboxylic acid and 1-carba-3-hydroxy-3-cephem-4-carboxylic acid and esters thereof are provided by a process comprising a rhodium C.sub.2 -C.sub.10 carboxylate catalyzed cyclization of an ester of a 4-(1-alkoxy- or 1-substituted alkoxy)-2-oxo-4-azetidinyl)-.beta.-ketobutyric acid and an ester of a 5-(1-alkoxy- or 1-substituted alkoxy-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketovaleric acid respectively. The process is carried out in an inert organic solvent at a temperature between about 15.degree. C. and about 85.degree. C. The 1-carba bicyclic .beta.-lactams are intermediates for preparing antibiotics.
- Creator
- Marvin J. Miller, Matthew A. Williams
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller, Yanping Xu
- Patent Number:
- US 6310058 B2
- Description:
Compounds represented by the formula [1] ##STR1## R.sub.1 is H or a substituent; R.sub.2 and R.sub.3 are C.sub.1 -C.sub.3 alkyl; R.sub.4 is siderophore group e.g. CH.sub.3 –(CH.sub.2).sub.n –C(O)–N(OH)–(CH.sub.2).sub.m – with n=10-22, m=2-6; X is O, S, or NH; X.sub.1 is O or NH; Y is H or alkyl; Z is H or substituted amino, e.g., t-BocNH or CbzNH, and r is 2-4; are useful in the method provided for treating tuberculosis. [1] is prepared by coupling [7], wherein HX.sub.1 is HO– or H.sub….
- Date Issued:
- 2001-10-30
- Record Visibility:
- Public
- Title
- Antimycobacterial agents
- Description
- Compounds represented by the formula [1] ##STR1## R.sub.1 is H or a substituent; R.sub.2 and R.sub.3 are C.sub.1 -C.sub.3 alkyl; R.sub.4 is siderophore group e.g. CH.sub.3 --(CH.sub.2).sub.n --C(O)--N(OH)--(CH.sub.2).sub.m -- with n=10-22, m=2-6; X is O, S, or NH; X.sub.1 is O or NH; Y is H or alkyl; Z is H or substituted amino, e.g., t-BocNH or CbzNH, and r is 2-4; are useful in the method provided for treating tuberculosis. [1] is prepared by coupling [7], wherein HX.sub.1 is HO-- or H.sub.2 N--, ##STR2## with [4] obtained as the free acid after saponification of the methyl ester.
- Creator
- Marvin J. Miller, Yanping Xu
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller
- Patent Number:
- US 4565654 B2
- Description:
Process for N-acyloxy or sulfooxy 2-azetidinones comprising O-acylation of a .beta.-hydroxy or .beta.-halo hydroxamic acid, and cyclizing the O-acylhydroxamate with TPP-CCl.sub.4 -TEA or with TPP-dialkylazodicarboxylate to the N-acyloxy-2-azetidinone. Solvolysis of the acyl group provides an N-hydroxy-2-azetidinone. E.g., N-Cbz-L-serine is converted to the O-acetyl hydroxamate, cyclized and solvolyzed to N-hydroxy-3-(Cbz-amino)-2-azetidinone. The N-hydroxy-2-azetidinones are useful intermedia…
- Date Issued:
- 1986-01-21
- Record Visibility:
- Public
- Title
- N-Acyloxy monocyclic .beta.-lactams
- Description
- Process for N-acyloxy or sulfooxy 2-azetidinones comprising O-acylation of a .beta.-hydroxy or .beta.-halo hydroxamic acid, and cyclizing the O-acylhydroxamate with TPP-CCl.sub.4 -TEA or with TPP-dialkylazodicarboxylate to the N-acyloxy-2-azetidinone. Solvolysis of the acyl group provides an N-hydroxy-2-azetidinone. E.g., N-Cbz-L-serine is converted to the O-acetyl hydroxamate, cyclized and solvolyzed to N-hydroxy-3-(Cbz-amino)-2-azetidinone. The N-hydroxy-2-azetidinones are useful intermediates to monocyclic .beta.-lactam antibiotics and .beta.-lactamase inhibitors.
- Creator
- Marvin J. Miller
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent
-
- Inventor(s):
- Marvin J. Miller, Garrett C. Moraski, Jonathan Stefely
- Patent Number:
- US 8268874 B2
- Description:
Embodiments relate to the field of chemistry and biochemistry, and, more specifically, to anti-cancer compounds, synthesis thereof, and methods of using same. Disclosed herein are various heterocyclic compounds and methods of using the novel anti-cancer compounds to inhibit the growth of a cancer cell, for instance a leukemia, non-small cell lung, central nervous system (CNS), skin, ovarian, renal, prostate, breast, or colon cancer cell. Other embodiments include methods of treating cancer in…
- Date Issued:
- 2012-09-18
- Record Visibility:
- Public
- Title
- Anti-cancer compounds, synthesis thereof, and methods of using same
- Description
- Embodiments relate to the field of chemistry and biochemistry, and, more specifically, to anti-cancer compounds, synthesis thereof, and methods of using same. Disclosed herein are various heterocyclic compounds and methods of using the novel anti-cancer compounds to inhibit the growth of a cancer cell, for instance a leukemia, non-small cell lung, central nervous system (CNS), skin, ovarian, renal, prostate, breast, or colon cancer cell. Other embodiments include methods of treating cancer in a subject, such as using the disclosed heterocyclic anti-cancer agents.
- Creator
- Marvin J. Miller, Garrett C. Moraski, Jonathan Stefely
- Publisher
- United States Patent and Trademark Office
- Language
- eng
- Rights
- http://creativecommons.org/publicdomain/zero/1.0/
- Resource Type
- Patent